Triethylamine → N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1-pyridin-4-ylazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 271952

反応式

HRID 271952 の反応式
C(N(CC)CC)C.[NH2:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:12][N:11]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)[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>>[F:23][C:17]1[C:18]([F:22])=[CH:19][CH:20]=[CH:21][C:16]=1[C@H:13]1[CH2:12][N:11]([C:24]2[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=2)[C:10](=[O:30])[C@H: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])[CH2:15][CH2:14]1

参加物

5

反応物 4

HCID 8471Triethylamine2 回HCID 821294-Nitrophenyl chloroformateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 60037853(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-pyridin-4-ylazepan-2-one

生成物 1

HCID 9807924N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1-pyridin-4-ylazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide収率 71.5%

実験手順

Triethylamine (0.018 mL, 0.132 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-pyridin-4-ylazepan-2-one (42 mg, 0.132 mmol) and 4-nitrophenyl chloroformate (27 mg, 0.132 mmol) in tetrahydrofaran (2 mL) at 0° C. After 1 h, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (38 mg, 0.132 mmol) and triethylamine (0.054 mL, 0.396 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→95% dichloromethane/methanol (10% ammonium hydroxide/methanol)] gave the title compound (53 mg). QQThe title compound was converted to the HCl salt with 2M HCl in ether. MS 562.2 (M+1). 1H NMR (500 MHz, CD3OD) δ 8.76 (d, J=7.6 Hz, 2H), 8.11 (d, J=7.3 Hz, 2H), 8.00 (d, J=6.4 Hz, 2H), 7.30 (t, J=7.0 Hz, 1H), 7.27-7.21 (m, 3H), 5.11 (d, J=11.5 Hz, 1H), 4.72-4.65 (m, 1H), 4.60-4.55 (m, 1H), 4.35-4.33 (m, 2H), 4.14 (d, J=16.1 Hz, 1H), 3.42-3.39 (m, 1H), 3.09-3.02 (m, 2H), 2.47-2.44 (m, 1H), 2.37-2.30 (m, 2H), 2.24-2.18 (m, 2H), 2.06-2.03 (m, 1H), 1.91 (br. s, 2H).

後処理

  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→95% dichloromethane/methanol (10% ammonium hydroxide/methanol)]

出典と根拠

ORDレコード
ord-d535e3e5bf3d4fd495e6501341c53d5c
出典データセット
uspto-grants-2008_11
特許番号
US07452903B2

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