Hydrochloric Acid → 5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-methoxy-5 trifluoromethyl-phenyl)-amide

HRID 45077

反応式

HRID 45077 の反応式
C(OC([N:8]1[CH2:16][C:15]2[C:14]([O:17][C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[NH:23][CH:22]=[CH:21]4)=[N:13][CH:12]=[N:11][C:10]=2[CH2:9]1)=O)(C)(C)C.C1N=CN([C:32]([N:34]2C=N[CH:36]=[CH:35]2)=[O:33])C=1.[CH3:39][O:40][C:41]1[CH:42]=C(N)C=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=1.Cl.C(O)(C(F)(F)F)=O>CN(C=O)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH3:39][O:40][C:41]1[CH:42]=[C:35]([NH:34][C:32]([N:23]2[C:24]3[C:20](=[CH:19][C:18]([O:17][C:14]4[C:15]5[CH2:16][NH:8][CH2:9][C:10]=5[N:11]=[CH:12][N:13]=4)=[CH:26][CH:25]=3)[CH:21]=[CH:22]2)=[O:33])[CH:36]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=1

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 6056715-(Trifluoromethyl)-m-anisidineHCID 59394637Tert-butyl 4-(1H-indol-5-yloxy)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

生成物 1

HCID 593944905-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-methoxy-5 trifluoromethyl-phenyl)-amide

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a solution of 4-(1H-indol-5-yloxy)-5,7-dihydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester (158 mg, 0.44 mmol) in DMF (4 mL), CDI (145 mg, 0.89 mmol) is added in one portion, followed by TEA (0.37 mL, 2.7 mmol). After 3 h at rt, 3-methoxy-5-trifluoromethyl-phenylamine (514 mg, 2.7 mmol) and DMAP (5.5 mg, 0.04 mmol) are added and the reaction is left stirring for 40 h. Ethyl acetate (2 mL) is added followed by the addition of 1 N HCl solution (3 mL). The organics are extracted with EtOAc (×3) and concentrated. The crude mixture is dissolved in CH2Cl2 (10 mL) and cooled to 0° C. and TFA (10 mL, 130 mmol) is added. The reaction is allowed to reach it over 2 h. The reaction mixture is evaporated, redissolved in EtOAc and few drops of NH4OH are added to freebase the amine. The solvent is removed and the residue separated by FCC (DCM/MeOH/NH4OH (100:0:0 to 93:6:1)) to give 5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-methoxy-5 trifluoromethyl-phenyl)-amide. MS (ESI) m/z 471.0 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.50-8.56 (m, 1 H)7.93 (d, J=3.54 Hz, 1 H)7.59 (d, J=19.71 Hz, 2 H)7.42 (d, J=2.27 Hz, 1 H)7.12 (dd, J=8.97, 2.40 Hz, 1 H)6.96 (s, 1 H)6.73 (d, J=3.79 Hz, 1 H)6.52 (s, 1 H)4.19 (d, J=8.34 Hz, 4 H)3.76 (s, 3 H)

後処理

  1. waitthe reaction is left
  2. extractionThe organics are extracted with EtOAc (×3)
  3. concentrationconcentrated
  4. dissolutionThe crude mixture is dissolved in CH2Cl2 (10 mL)
  5. customover 2 h
  6. customThe reaction mixture is evaporated
  7. dissolutionredissolved in EtOAc
  8. additionfew drops of NH4OH are added
  9. customThe solvent is removed
  10. customthe residue separated by FCC (DCM/MeOH/NH4OH (100:0:0 to 93:6:1))

出典と根拠

ORDレコード
ord-a6eb976235d947c2b1a3cced16d0ef26
出典データセット
uspto-grants-2013_09
特許番号
US08541432B2

関連ノート

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