A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance

Table 3

¹H and ¹³C chemical shifts (δ/ppm) of the enriched impurity fraction in DMSO-d6.

	^1H (𝛿/ppm, J/Hz)^(a)		^13C (𝛿/ppm)^(a)
Position	Unknown 2	Unknown 1	Unknown 2	Unknown 1
1			131.0 (q, ^2JC-F = 31.7 Hz)	131.0 (q, ^2JC-F = 31.7 Hz)
2, 6	7.92 (d, 2H, J = 8.3 Hz)	7.95 (d, 2H, J = 8.3 Hz)	125.9	125.9
3, 5	8.45 (d, 2H, J = 8.3 Hz)	8.50 (d, 2H, J = 8.3 Hz)	128.0	128.0
4			139.6	139.6
7			163.6	163.5
9	8.81 (s, 1H)	8.89 (s, 1H)	158.5	158.6^(b)
11			170.1	170.2
12	8.00 (s, 1H)	8.11 (s, 1H)	104.2	104.4
13			124.0 (q, ^1JC-F = 273.2 Hz)	124.0 (q, ^1JC-F = 273.2 Hz)
15			143.7	143.5
16	7.45 (d, 1H, J = 8.2 Hz)	7.59 (d, 1H, J = 8.0 Hz)	120.4	119.9
17	7.49 (d, 1H, J = 8.2 Hz)	7.68 (d, 1H, J = 8.0 Hz)	128.1	123.9
18			122.6	131.2
19			136.6	132.8
20			141.6	141.9
22			158.5	158.4^(b)
24	12.54 (s, 1H)	12.55 (s, 1H)
25			169.7	169.7
26	2.12 (s, 3H)	2.13 (s, 3H)	22.5	22.6

^(a) Signal splitting pattern: s = singlet, d = doublet, q = quartet; ^(b) interchangeable assignments.