Triethylamine → N-[1-(2,3-Difluorobenzyl)-5-oxo-4-(2,2,2-trifluoroethyl)-1,4-diazepan-6-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 967607

반응식

HRID 967607 반응식
C(N(CC)CC)C.[NH2:8][CH:9]1[CH2:15][N:14]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=2[F:24])[CH2:13][CH2:12][N:11]([CH2:25][C:26]([F:29])([F:28])[F:27])[C:10]1=[O:30].Cl[C:32](OC1C=CC([N+]([O-])=O)=CC=1)=[O:33].Cl.Cl.[O:46]=[C:47]1[NH:55][C:50]2=[N:51][CH:52]=[CH:53][CH:54]=[C:49]2[N:48]1[CH:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1>O1CCCC1>[F:24][C:18]1[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:17]=1[CH2:16][N:14]1[CH2:15][CH:9]([NH:8][C:32]([N:59]2[CH2:60][CH2:61][CH:56]([N:48]3[C:49]4[C:50](=[N:51][CH:52]=[CH:53][CH:54]=4)[NH:55][C:47]3=[O:46])[CH2:57][CH2:58]2)=[O:33])[C:10](=[O:30])[N:11]([CH2:25][C:26]([F:28])([F:29])[F:27])[CH2:12][CH2:13]1

참가 물질

6

반응물 4

HCID 8471Triethylamine2회HCID 821294-Nitrophenyl chloroformateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 222932496-Amino-1-(2,3-difluorobenzyl)-4-(2,2,2-trifluoroethyl)-1,4-diazepan-5-one

생성물 1

HCID 22293161N-[1-(2,3-Difluorobenzyl)-5-oxo-4-(2,2,2-trifluoroethyl)-1,4-diazepan-6-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide수율 86.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Triethylamine (0.012 mL, 0.133 mmol) was added to a solution of 6-amino-1-(2,3-difluorobenzyl)-4-(2,2,2-trifluoroethyl)-1,4-diazepan-5-one (45 mg, 0.133 mmol) and 4-nitrophenyl chloroformate (27 mg, 133 mmol) in tetrahydrofuran (2.5 mL) at 0° C. After 1 h, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (43 mg, 0.147 mmol) and triethylamine (0.048 mL, 0.532 mmol) were added and the mixture allowed to warm to ambient temperature. After 18 h, the mixture was partitioned between ethyl acetate and water. The organic layer was washed with water (2×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography [100% dichloromethane→92% dichloromethane/methanol (10% ammonium hydroxide/methanol)] gave the title compound (67 mg). MS 582.2262 (M+1). 1H NMR (500 MHz, CDCl3) δ 8.77 (s, 1H), 8.03 (d, J=5.4 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 7.27-7.24 (m, 1H), 7.09-7.05 (m, 2H), 6.98 (dd, J=8.1, 5.4 Hz, 1H), 5.99 (d, J=4.9 Hz, 1H), 4.91-4.88 (m, 1H), 4.57-4.50 (m, 1H), 4.25-4.16 (m, 3H), 4.00-3.92 (m, 2H), 3.84 (dd, J=32.7, 14.2 Hz, 2H), 3.36-3.34 (m, 1H), 3.20 (d, J=12.5 Hz, 1H), 2.99-2.91 (m, 3H), 2.44-2.37 (m, 2H), 2.31-2.18 (m, 2H), 1.90 (d, J=11.0 Hz, 2H).

후처리

  1. waitAfter 18 h
  2. customthe mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water (2×), saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography [100% dichloromethane→92% dichloromethane/methanol (10% ammonium hydroxide/methanol)]

출처 및 근거

ORD 기록
ord-4fb6fcc12e9d4235bf3ba3d1cc9b042c
출처 데이터셋
uspto-grants-2005_10
특허 번호
US06953790B2

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