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

HRID 20162

反応式

HRID 20162 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]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)[C:10]1=[O:31].Cl[C:33](OC1C=CC([N+]([O-])=O)=CC=1)=[O:34].Cl.Cl.[O:47]=[C:48]1[NH:56][C:51]2=[N:52][CH:53]=[CH:54][CH:55]=[C:50]2[N:49]1[CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>O1CCCC1>[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]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)[C:10](=[O:31])[C@H:9]([NH:8][C:33]([N:60]2[CH2:61][CH2:62][CH:57]([N:49]3[C:50]4[C:51](=[N:52][CH:53]=[CH:54][CH:55]=4)[NH:56][C:48]3=[O:47])[CH2:58][CH2:59]2)=[O:34])[CH2:15][CH2:14]1

参加物

6

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 60037848(3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(pyridin-2-ylmethyl)azepan-2-one

生成物 1

HCID 11387595N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(pyridin-2-ylmethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide収率 100%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Triethylamine (0.065 mL, 0.468 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(pyridin-2-ylmethyl)azepan-2-one (180 mg, 0.417 mmol) and 4-nitrophenyl chloroformate (94 mg, 0.468 mmol) in tetrahydrofuran (3 mL) at 0° C. After 1 h, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (136 mg, 0.468 mmol) and triethylamine (0.195 mL, 1.404 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 (240 mg). The title compound was converted to the HCl salt with 2M HCl in ether. MS 576.3 (M+1). 1H NMR (500 MHz, CD3OD) δ 8.78 (d, J=5.9 Hz, 1H), 8.62-8.59 (m, 1H), 8.07 (d, J=8.3 Hz, 1H), 8.03-7.98 (m, 3H), 7.32 (dd, J=8.1 Hz, 6.1, 1H), 7.18-7.15 (m, 3H), 5.43 (d, J=16.9 Hz, 1H), 4.75 (d, J=17.1 Hz, 1H), 4.56-4.51 (m, 1H), 4.36-4.28 (m, 3H), 3.51 (d, J=15.1 Hz, 1H), 3.48 (s, 1H), 3.22-3.17 (m, 1H), 3.05-2.98 (m; 2H), 2.44-2.40 (m, 1H), 2.34-2.23 (m, 2H), 2.18-2.14 (m, 2H), 1.97-1.92 (m, 1H), 1.89-1.88 (m, 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-387952773f3e44c8a844e5a243c9ec3a
出典データセット
uspto-grants-2010_06
特許番号
US07745427B2

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