1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(adamantan-1-ylmethoxy)-N-((3-cyanoazetidin-1-yl)sulfonyl)-5-cyclopropyl-2-fluorobenzamide

HRID 1849671ノート

反応式

HRID 1849671 の反応式
[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:24][CH2:23]4)=[CH:20][C:16]([C:17]([OH:19])=O)=[C:15]([F:25])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(N=C=NCCCN(C)C)C.[C:37]([CH:39]1[CH2:42][N:41]([S:43]([NH2:46])(=[O:45])=[O:44])[CH2:40]1)#[N:38]>CN(C)C1C=CN=CC=1.ClCCl>[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:23][CH2:24]4)=[CH:20][C:16]([C:17]([NH:46][S:43]([N:41]4[CH2:42][CH:39]([C:37]#[N:38])[CH2:40]4)(=[O:45])=[O:44])=[O:19])=[C:15]([F:25])[CH:14]=3)[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2

参加物

6

反応物 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 867028614-(Adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoic acidHCID 867035383-Cyanoazetidine-1-sulfonamide

生成物 1

HCID 867035374-(adamantan-1-ylmethoxy)-N-((3-cyanoazetidin-1-yl)sulfonyl)-5-cyclopropyl-2-fluorobenzamide収率 79%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

To a mixture of 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoic acid (0.20 g, 0.60 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.26 g, 1.38 mmol) and 4-dimethylaminopyridine (0.17 g, 1.38 mmol) in anhydrous dichloromethane (10 mL) was added 3-cyanoazetidine-1-sulfonamide (0.22 g, 1.38 mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The mixture was quenched with 1 M aqueous hydrochloride acid (30 mL) followed by extraction with ethyl acetate (100 mL). The organic layer was washed with water (30 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo, the residue was purified by silica gel column chromatography using 10-60% ethyl acetate (containing 2% acetic acid) in hexanes as an elute to afford the title compound as colorless solid (0.23 g, 79%): 1H NMR (300 MHz, DMSO-d6) δ 11.88 (s, 1H), 7.18 (d, J=8.3 Hz, 1H), 6.95 (d, J=13.0 Hz, 1H), 4.35-4.22 (m, 4H), 3.84-3.74 (m, 1H), 3.65 (s, 2H), 2.09-1.99 (m, 4H), 1.75-1.67 (m, 12H), 0.95-0.87 (m, 2H), 0.70-0.65 (m, 2H); MS (ES+) m/z 488.2 (M+1); MS (ES−) m/z 486.3 (M−1).

後処理

  1. customThe mixture was quenched with 1 M aqueous hydrochloride acid (30 mL)
  2. extractionfollowed by extraction with ethyl acetate (100 mL)
  3. washThe organic layer was washed with water (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by silica gel column chromatography
  8. washan elute

出典と根拠

ORDレコード
ord-7ba5aec6f2ab40e49492bba6231c7c69
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

読み込み中…