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 75618노트

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HRID 75618 반응식
[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

참가 물질

5

반응물 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

생성물 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-ylamine수율 52%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

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+].

후처리

  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

출처 및 근거

ORD 기록
ord-170d50b756ae440c9e1971b0ee219642
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835431B2

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