Sodium hydride → (1S,3S)-3-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-indan-1-ylamine

HRID 1402153노트

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HRID 1402153 반응식
[NH2:1][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:4]([OH:11])[CH2:3]1.[H-].[Na+].F[C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([C@@H:24]3[CH2:28][CH2:27][CH2:26][N:25]3[CH3:29])=[N:22][N:23]=2)[CH:20]=1>CN(C=O)C.O>[CH3:29][N:25]1[CH2:26][CH2:27][CH2:28][C@H:24]1[C:21]1[N:19]2[CH:20]=[C:15]([O:11][C@@H:4]3[C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[C@@H:2]([NH2:1])[CH2:3]3)[CH:16]=[CH:17][C:18]2=[N:23][N:22]=1

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 12013033(1S,3S)-3-Amino-2,3-dihydro-1H-inden-1-olHCID 866870156-Fluoro-3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine

생성물 1

HCID 86687014(1S,3S)-3-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-indan-1-ylamine

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

(1S,3S)-3-Amino-indan-1-ol (110 mg, 0.74 mmol) was added to a suspension of NaH (60% in mineral oil, 87 mg, 2.17 mmol) in anhydrous DMF (5 mL) at RT and stirred for 20 min. Intermediate 5b (160 mg, 0.72 mmol) was then added in one portion and the mixture heated at 60° C. for 3 h. After cooling the mixture was diluted with water (20 mL) and extracted with EtOAc (3×50 mL). The combined organics were washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give the title compound as give a foam (132 mg, 52%). LCMS (Method 1): Rt 0.34 min, m/z 350 [MH+]. 1H NMR (300 MHz, CDCl3): 1.95-2.16 (6H, m), 2.24 (3H, s), 2.26-2.45 (2H, m), 2.77 (1H, ddd, J 14.1, 7.0, 2.0), 3.23-3.30 (1H, m), 4.02-4.09 (1H, m), 4.71 (1H, t, J 6.8), 5.68 (1H, dd, J 6.2, 1.9), 7.04 (1H, dd, J 9.9, 2.2), 7.29-7.50 (4H, m), 7.64 (1H, dd, J 9.9, 0.9), 8.35 (1H, d, J 2.2).

후처리

  1. temperatureAfter cooling the mixture
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organics were washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by FCC

출처 및 근거

ORD 기록
ord-dfa33627bc3b4b2f8b462f8682c460dc
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08907094B2

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