Trifluoroacetic acid → (+/-)-5-[6-(3-Carbamoyl-pyrrolidin-1-ylmethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 1887614

反応式

HRID 1887614 の反応式
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13](=[O:15])[NH2:14])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.[F:23][C:24]([F:57])([F:56])[C:25]1[CH:26]=[C:27]([NH:31][C:32]([N:34]2[C:42]3[C:37](=[CH:38][C:39]([O:43][C:44]4[N:49]=[CH:48][N:47]=[C:46](COS(C)(=O)=O)[CH:45]=4)=[CH:40][CH:41]=3)[CH:36]=[CH:35]2)=[O:33])[CH:28]=[CH:29][CH:30]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:56][C:24]([F:23])([F:57])[C:25]1[CH:26]=[C:27]([NH:31][C:32]([N:34]2[C:42]3[C:37](=[CH:38][C:39]([O:43][C:44]4[CH:45]=[C:46]([CH2:6][N:8]5[CH2:12][CH2:11][CH:10]([C:13](=[O:15])[NH2:14])[CH2:9]5)[N:47]=[CH:48][N:49]=4)=[CH:40][CH:41]=3)[CH:36]=[CH:35]2)=[O:33])[CH:28]=[CH:29][CH:30]=1

参加物

6

反応物 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 4571096Tert-butyl 3-carbamoylpyrrolidine-1-carboxylateHCID 46224264methanesulfonic acid 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl ester

生成物 1

HCID 59394341(+/-)-5-[6-(3-Carbamoyl-pyrrolidin-1-ylmethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

3-Carbamoyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.22 g, 1.03 mmol) is dissolved in DCM (5 mL). TFA (2 mL, 26.0 mmol) is added and the reaction is allowed to stir at rt overnight. The solvent is removed in vacuo and THF (5.0 mL) is added followed by methanesulfonic acid 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl ester (0.347 g, 0.685 mmol) and DIEA (0.60 mL, 3.42 mmol). The reaction is heated at 60° C. for 19 h. The solvent is removed in vacuo and the residue separated by FCC (0-15%, 10% NH3MeOH/DCM) to provide (±)-5-[6-(3-carbamoyl-pyrrolidin-1-ylmethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 524.9 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.41 (s, 1H), 8.72 (s, 1H), 8.30 (d, J=8.84 Hz, 1H), 8.14 (d, J=3.79 Hz, 1H), 8.10 (s, 1H), 7.97 (s, 1H), 7.65 (t, J=8.08 Hz, 1H), 7.51 (d, J=2.53 Hz, 2H), 7.16 (dd, J=8.84, 2.27 Hz, 1H), 7.12 (s, 1H), 6.81 (d, J=3.54 Hz, 1H), 3.63 (br. S., 1H), 3.14 (d, J=7.33 Hz, 1H), 2.94 (br. S., 1H), 1.99 (br. S., 1H), 1.25 (d, J=6.06 Hz, 6H).

後処理

  1. customThe solvent is removed in vacuo and THF (5.0 mL)
  2. additionis added
  3. temperatureThe reaction is heated at 60° C. for 19 h
  4. customThe solvent is removed in vacuo
  5. customthe residue separated by FCC (0-15%, 10% NH3MeOH/DCM)

出典と根拠

ORDレコード
ord-dd2079801ec343339a8ea1e9975925a3
出典データセット
uspto-grants-2013_08
特許番号
US08501756B2

関連ノート

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