Ammonia → (1S,4S)-4-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 1402231노트

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HRID 1402231 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]([C@@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3[CH3:30])=[N:23][N:24]=2)[CH:21]=1.N>CN(C=O)C.O.CO.C(Cl)Cl>[CH3:30][N:26]1[CH2:27][CH2:28][CH2:29][C@H:25]1[C:22]1[N:20]2[CH:21]=[C:16]([O:12][C@@H:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C@@H:2]([NH2:1])[CH2:3][CH2:4]3)[CH:17]=[CH:18][C:19]2=[N:24][N:23]=1

참가 물질

9

반응물 4

HCID 222AmmoniaHCID 24758Sodium hydrideHCID 86686682(1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 866870156-Fluoro-3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine

생성물 1

HCID 86687083(1S,4S)-4-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매

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온도
60 °C

실험 절차

A solution of Intermediate B (179 mg, 1.10 mmol) in dry DMF (2.5 mL) was added NaH (60% in mineral oil, 333 mg, 5.00 mmol) at RT and stirred for 15 min. Intermediate 5b (220 mg, 1.00 mmol) in DMF (2.5 mL) was then added and the mixture heated at 60° C. for 1 h. After cooling, the resulting dark brown mixture was diluted with water and extracted with DCM. The combined organics were dried and concentrated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give a residue. FCC, using 0-10% [2M NH3 in MeOH] in DCM, gave the title compound as light brown powder after freeze drying (224 mg, 61%). LCMS (Method 3): Rt 1.34 min, m/z 364 [MH+].

후처리

  1. temperatureAfter cooling
  2. extractionextracted with DCM
  3. customThe combined organics were dried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by FCC
  6. customto give a residue

출처 및 근거

ORD 기록
ord-db848948cb964bb183f826b5c52d08f0
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08907094B2

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