Triethylamine → N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(8-oxo-8,9-dihydro-7H-purin-7-yl)piperidine-1-carboxamide

HRID 271954ノート

反応式

HRID 271954 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]([F:28])([F:27])[F:26])[C:10]1=[O:29].Cl[C:31](OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].Cl.[NH:44]1[CH2:49][CH2:48][CH:47]([N:50]2[C:58]3[C:53](=[N:54][CH:55]=[N:56][CH:57]=3)[NH:52][C:51]2=[O:59])[CH2:46][CH2:45]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]([F:28])([F:26])[F:27])[C:10](=[O:29])[C@H:9]([NH:8][C:31]([N:44]2[CH2:49][CH2:48][CH:47]([N:50]3[C:58]4[C:53](=[N:54][CH:55]=[N:56][CH:57]=4)[NH:52][C:51]3=[O:59])[CH2:46][CH2:45]2)=[O:32])[CH2:15][CH2:14]1

参加物

6

反応物 4

HCID 8471Triethylamine2 回HCID 821294-Nitrophenyl chloroformateHCID 222931977-Piperidin-4-yl-7,9-dihydro-8H-purin-8-one hydrochlorideHCID 23653826(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one

生成物 1

HCID 11169053N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(8-oxo-8,9-dihydro-7H-purin-7-yl)piperidine-1-carboxamide収率 92.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Triethylamine (0.030 mL, 0.215 mmol) was added to a solution of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one (80 mg, 0.248 mmol) and 4-nitrophenyl chloroformate (44 mg, 0.218 mmol) in tetrahydrofuran (3 mL) at 0° C. After 0.5 h, 7-piperidin-4-yl-7,9-dihydro-8H-purin-8-one hydrochloride (73 mg, 0.248 mmol) and triethylamine (0.120 mL, 0.860 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) gave the title compound (114 mg). MS 567.2123 (M+1).

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)

出典と根拠

ORDレコード
ord-7f572622460f4cae99b1ec405cc78d83
出典データセット
uspto-grants-2008_11
特許番号
US07452903B2

反応ノート

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