Sodium hydride → (1S,4R)-4-[3-(2-Chloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 572108ノート

反応式

HRID 572108 の反応式
[H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]1[N:26]2[CH:27]=[C:28](F)[CH:29]=[CH:30][C:25]2=[N:24][N:23]=1>CN(C=O)C>[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]1[N:26]2[CH:27]=[C:28]([O:14][C@H:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C@@H:4]([NH2:3])[CH2:5][CH2:6]3)[CH:29]=[CH:30][C:25]2=[N:24][N:23]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 848195603-(2-Chlorophenyl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridineHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-ol

生成物 1

HCID 86686723(1S,4R)-4-[3-(2-Chloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine収率 52%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

Sodium hydride (60% in mineral oil, 840 mg, 21.9 mmol) was added portionwise to a stirred solution of Intermediate 1d (1.19 g, 7.31 mmol) in anhydrous DMF (30 mL) at RT under an argon atmosphere. Intermediate 31b (1.81 g, 7.31 mmol) was then added, and stirring at 60° C. was continued for 1.5 h. After cooling, the reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl and extracted with EtOAc (×2). The combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC, using 0-10% MeOH in DCM to afford the title compound (1.48 g, 52%) as a brown foam. LCMS (Method 3): Rt 0.42 and 2.33 min, m/z 391. [MH+].

後処理

  1. temperatureAfter cooling
  2. customthe reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl
  3. extractionextracted with EtOAc (×2)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by FCC

出典と根拠

ORDレコード
ord-9b2ba8b6c88e45c68996617f5e06fd67
出典データセット
uspto-grants-2015_05
特許番号
US09029373B2

反応ノート

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