Cyclopropanecarboxylic acid → N-(5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)cyclopropanecarboxamide

HRID 64164

반응식

HRID 64164 반응식
[CH:1]1([CH2:4][N:5]2[CH:9]=[C:8]([C:10]3[CH:11]=[C:12]4[N:18]=[CH:17][N:16]([C:19]5[CH:20]=[C:21]([NH2:33])[CH:22]=[C:23]([C:25]6[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=6[F:32])[CH:24]=5)[C:13]4=[N:14][CH:15]=3)[N:7]=[N:6]2)[CH2:3][CH2:2]1.[CH:34]1([C:37](O)=[O:38])[CH2:36][CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:1]1([CH2:4][N:5]2[CH:9]=[C:8]([C:10]3[CH:11]=[C:12]4[N:18]=[CH:17][N:16]([C:19]5[CH:20]=[C:21]([NH:33][C:37]([CH:34]6[CH2:36][CH2:35]6)=[O:38])[CH:22]=[C:23]([C:25]6[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=6[F:32])[CH:24]=5)[C:13]4=[N:14][CH:15]=3)[N:7]=[N:6]2)[CH2:2][CH2:3]1

참가 물질

6

반응물 4

HCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 895014685-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo-[4,5-b]pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-amine

생성물 1

HCID 117777721N-(5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)cyclopropanecarboxamide수율 51%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo-[4,5-b]pyridin-3-yl)-2′,4′-difluoro-[1,1′-biphenyl]-3-amine (50 mg, 0.11 mmol) in DMF was added cyclopropanecarboxylic acid (11 mg, 0.13, mmol, 1.2 eq.) followed by HATU (91 mg, 0.24 mmol, 2.0 eq.) and DIPEA (43 mg, 0.33 mmol, 3.0 eq). The mixture was stirred for 16 h and quenched extracted as in Example 1(d). The solvent was distilled off to afford the crude residue which was purified by column chromatography to give the product in 51% yield (25 mg). 1H NMR (300 MHz, DMSO): δ 10.6 (s, 1H) 8.99 (d, 2H), 8.88 (d, 1H), 8.62 (d, 1H), 8.31 (d, 1H), 7.92 (d, 1H), 7.76-7.71 (m, 2H), 7.47-7.40 (m, 1H), 7.29-7.24 (m, 1H), 4.33-4.30 (d, 2H), 3.64-3.62 (m, 2H), 3.12-3.09 (m, 2H), 1.87-1.83 (m, 1H), 0.63-0.61 (t, 2H), 0.49-0.48 (t, 2H); LC-MS (ESI): Calculated mass: 511.5; Observed mass: 511.8 [M+H]+ (rt: 1.63 min).

후처리

  1. customquenched
  2. extractionextracted as in Example 1(d)
  3. distillationThe solvent was distilled off

출처 및 근거

ORD 기록
ord-98ad2478c42841e9a426b0ef13b49c4e
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447091B2

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