1,2-Dichloroethane → HCID 56654309、化合物

HRID 242327

反応式

HRID 242327 の反応式
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:24][CH2:23][C:12]3[N:13]=[CH:14][N:15]=[C:16]([O:17][C@H:18]4[CH2:22][CH2:21][NH:20][CH2:19]4)[C:11]=3[CH2:10]2)=[CH:5][C:4]=1[C:25]([F:28])([F:27])[F:26].[CH3:29][N:30]1[CH:34]=[C:33]([C:35](O)=[O:36])[CH:32]=[N:31]1.N1(O)C2C=CC=CC=2N=N1.C(Cl)CCl>C(Cl)Cl>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:24][CH2:23][C:12]3[N:13]=[CH:14][N:15]=[C:16]([O:17][C@H:18]4[CH2:22][CH2:21][N:20]([C:35]([C:33]5[CH:32]=[N:31][N:30]([CH3:29])[CH:34]=5)=[O:36])[CH2:19]4)[C:11]=3[CH2:10]2)=[CH:5][C:4]=1[C:25]([F:28])([F:26])[F:27]

参加物

6

反応物 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 6431601-Methyl-1H-pyrazole-4-carboxylic acidHCID 57495337HCID 57495337、化合物2 回

生成物 1

HCID 56654309HCID 56654309、化合物

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a mixture of 6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (prepared using step 1, example 91 from intermediate 13) (44 mg, 0.11 mmol), 1-methyl-1H-pyrazole-4-carboxylic acid (15 mg, 0.12 mmol), benztriazol-1-ol (19 mg, 0.12 mmol) in CH2Cl2 (1.0 mL) was added EDC (34 mg, 0.18 mmol) and the resulting mixture was stirred at rt for 18 h. Partitioned between CH2Cl2 (10 mL) and sat. NaHCO3(aq) (2.0 mL) and the organic layer separated by filtering through a phase separation tube. Concentrated in vacuo and purified by flash chromatography through Biotage® amino silica gel eluting with cyclohexane/EtOAc, 100/0 to 0/100 to give {(S)-3-[6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidin-1-yl}-(1-methyl-1H-pyrazol-4-yl)-methanone as a white lyophilized powder (44 mg, 75% yield). 1H NMR (400 MHz, CDCl3-d, 298K) δ ppm 2.26-2.45 (m, 2H) 3.04-3.10 (m, 2H) 3.49-3.57 (m, 2H) 3.89-4.00 (m, 7H) 4.01 (s, 3H) 4.10-4.18 (m, 2H) 5.78-5.83 (m, 1H) 7.60-7.62 (m, 1H) 7.76-7.89 (m, 2H) 8.04-8.07 (m, 1H) 8.61-8.66 (m, 1H) MS: [M+H]+=504.2, Rt(3)=1.59 min. Example 55 was prepared using procedures analogous to those used in example 54 using appropriate starting materials.

後処理

  1. customPartitioned between CH2Cl2 (10 mL) and sat. NaHCO3(aq) (2.0 mL)
  2. customthe organic layer separated
  3. filtrationby filtering through a phase separation tube
  4. concentrationConcentrated in vacuo
  5. custompurified by flash chromatography through Biotage® amino silica gel eluting with cyclohexane/EtOAc, 100/0 to 0/100

出典と根拠

ORDレコード
ord-e207732812ac4d5998a15f8facdcc7b1
出典データセット
uspto-grants-2014_02
特許番号
US08653092B2

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