Triethylamine → phenyl N-[4-(3-fluoro-4-{[1-(phenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate

HRID 2265616ノート

反応式

HRID 2265616 の反応式
[C:1]1([O:7][C:8](=[O:34])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH2:32])=[C:28]([F:33])[CH:27]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:35]1([NH:41][C:42]([C:44]2([C:47](O)=[O:48])[CH2:46][CH2:45]2)=[O:43])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[C:1]1([O:7][C:8](=[O:34])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:47]([C:44]4([C:42](=[O:43])[NH:41][C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH2:45][CH2:46]4)=[O:48])=[C:28]([F:33])[CH:27]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:11])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 190968711-(Phenylcarbamoyl)cyclopropanecarboxylic acidHCID 67136032[4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

生成物 1

HCID 59596979phenyl N-[4-(3-fluoro-4-{[1-(phenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate収率 87.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A crude product of [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (219 mg) was dissolved in N,N-dimethylformamide (5 ml). 1-(Phenylcarbamoyl)cyclopropanecarboxylic acid (196 mg), triethylamine (0.133 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (422 mg) were added under a nitrogen atmosphere at room temperature, followed by stirring overnight. Liquid-liquid separation was carried out after addition of ethyl acetate and water to the reaction mixture. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was removed and the resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:2) to provide the titled compound as white powder (271 mg).

後処理

  1. customLiquid-liquid separation
  2. additionafter addition of ethyl acetate and water to the reaction mixture
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed
  6. customthe resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:2)

出典と根拠

ORDレコード
ord-610333e522e74125a987e76cfc84a07b
出典データセット
uspto-grants-2010_12
特許番号
US07855290B2

反応ノート

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