Ammonia → [6-((1R,4S)-4-Amino-1,2,3,4-tetrahydro-naphthalen-1-yloxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]-methyl-(2-morpholin-4-yl-ethyl)-amine

HRID 2282447노트

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HRID 2282447 반응식
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]([CH3:34])[CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[N:23][N:24]=2)[CH:21]=1.N>CN(C=O)C.CO.C(Cl)Cl>[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([O:12][C:16]2[CH:17]=[CH:18][C:19]3[N:20]([C:22]([N:25]([CH3:34])[CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[N:23][N:24]=3)[CH:21]=2)[CH2:4][CH2:3]1

참가 물질

8

반응물 4

HCID 222AmmoniaHCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687030(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-methyl-(2-morpholin-4-yl-ethyl)-amine

생성물 1

HCID 89612379[6-((1R,4S)-4-Amino-1,2,3,4-tetrahydro-naphthalen-1-yloxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]-methyl-(2-morpholin-4-yl-ethyl)-amine수율 51.1%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
60 °C

실험 절차

To a solution of Intermediate A (225 mg, 1.38 mmol) in DMF (3 mL) was added NaH (60% in oil, 150 mg, 3.75 mmol) and the mixture stirred at RT for 20 min, before Intermediate 45c (350 mg, 1.25 mmol) was added. This mixture was stirred at 60° C. for 7 h. The reaction mixture was applied to an SCX-2 cartridge (25 g) and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave a residue. FCC, using 0-20% [2M NH3 in MeOH] in DCM, gave the title compound as an orange oil (270 mg, 51%). LCMS (Method 4): Rt 0.22 min, m/z 423 [MH+].

후처리

  1. additionwas added
  2. washwashed with MeOH
  3. washThe product was eluted with 2M NH3 in MeOH
  4. concentrationconcentration in vacuo
  5. customgave a residue

출처 및 근거

ORD 기록
ord-aa16dfa66a16495abb907946c842b182
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09139584B2

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