Trifluoroacetic acid methylene chloride → Hydrochloric Acid
Reaction equation
[C:1]([C:4]1[C:5]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH:34]3[CH2:39][CH2:38][N:37](C(OC(C)(C)C)=O)[CH2:36][CH2:35]3)=[CH:30][C:29]=2[F:47])=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH2:13][C@@H:12]([NH:16][C:17](=[O:26])[C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[CH2:11]2)=[CH:8][N:9]=1)(=[O:3])[NH2:2].NC1C=CC(C2CCN(C(OC(C)(C)C)=O)CC2)=CC=1F.C(O)(C(F)(F)F)=O.C(Cl)[Cl:77]>>[F:47][C:29]1[CH:30]=[C:31]([CH:34]2[CH2:35][CH2:36][NH:37][CH2:38][CH2:39]2)[CH:32]=[CH:33][C:28]=1[NH:27][C:5]1[C:4]([C:1]([NH2:2])=[O:3])=[N:9][CH:8]=[C:7]([N:10]2[CH2:15][CH2:14][CH2:13][C@@H:12]([NH:16][C:17](=[O:26])[C:18]3[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)[CH2:11]2)[N:6]=1.[ClH:77]Participants
Procedure
In a similar manner as described in Example 110, (R)-tert-butyl 4-(4-(3-carbamoyl-6-(3-(4-methoxybenzamido)piperidin-1-yl)pyrazin-2-ylamino)-3-fluorophenyl)piperidine-1-carboxylate (200) was prepared using tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate. It was treated with 1:1 TFA/DCM at RT for 30 min, and (R)-3-(2-fluoro-4-(piperidin-4-yl)phenylamino)-5-(3-(4-methoxybenzamido)piperidin-1-yl)pyrazine-2-carboxamide (201) was isolated as HCl salt using reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases. MS found for C29H34FN7O3 as (M+H)+ 548.2, (M−H)− 546.3. UV: λ=257, 280, 306, 334, 369 nm. Proton NMR (CD3OD): δ 8.34 (1H, m), 7.79 (2H, d, J=9.0 Hz), 7.72 (1H, s), 7.03 (1H, d, J=12.5 Hz), 6.99 (2H, d, J=8.5 Hz), 6.96 (1H, d, J=9.5 Hz), 4.46 (1H, m), 4.18 (1H, m), 4.12 (1H, m), 3.86 (3H, m), 3.45 (1H, s), 3.42 (1H, s), 3.25 (2H, m), 3.08 (2H, m), 2.80 (1H, m), 2.11 (1H, m), 2.01-1.94 (3H, m), 1.81-1.70 (4H, m) ppm.
Workup
- customwas prepared
Sources & evidence
- ORD record
- ord-344ec08c2421406ba285aa2e8ca9ebc4
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09382246B2
Reaction notes
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