Diisopropylethylamine → tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate

HRID 1842608노트

반응식

HRID 1842608 반응식
[F:1][CH:2]([F:22])[O:3][C:4]1[CH:5]=[N:6][C:7]2[N:8]([N:10]=[CH:11][C:12]=2[C:13]2[CH:14]=[C:15]([C:19](O)=[O:20])[S:16][C:17]=2[CH3:18])[CH:9]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:50][C@H:51]1[C:56]([F:58])([F:57])[CH2:55][CH2:54][CH2:53][C@H:52]1[NH:59][C:60](=[O:66])[O:61][C:62]([CH3:65])([CH3:64])[CH3:63].C(N(C(C)C)CC)(C)C>CN(C=O)C.ClCCl>[C:62]([O:61][C:60](=[O:66])[NH:59][C@@H:52]1[CH2:53][CH2:54][CH2:55][C:56]([F:58])([F:57])[C@@H:51]1[NH:50][C:19]([C:15]1[S:16][C:17]([CH3:18])=[C:13]([C:12]2[CH:11]=[N:10][N:8]3[CH:9]=[C:4]([O:3][CH:2]([F:1])[F:22])[CH:5]=[N:6][C:7]=23)[CH:14]=1)=[O:20])([CH3:65])([CH3:63])[CH3:64]

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59603811tert-Butyl ((1R,2R)-2-amino-3,3-difluorocyclohexyl)carbamateHCID 683051734-[6-(Difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylic acid

생성물 1

HCID 89750994tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate수율 68.2%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

4-[6-(Difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylic acid (0.768 g, 2.36 mmol) and BOP (3.13 g, 7.08 mmol) were dissolved in DMF (15.7 mL) and stirred at room temperature for 5 min. To the reaction solution was added tert-butyl [(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (0.650 g, 2.60 mmol) and diisopropylethyl amine (619, 3.54 mmol) and the reaction stirred at room temperature for 16 h. The reaction mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate twice and brine once. The organic layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0-100% EtOAc/Hex) to give the title compound (0.900 g, 1.61 mmol). LRMS (APCI) calc'd for (C24H27F4N5O4S) [M+H]+, 558.2; found 558.0.

후처리

  1. stirringthe reaction stirred at room temperature for 16 h
  2. washwashed with saturated sodium bicarbonate twice
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography (0-100% EtOAc/Hex)

출처 및 근거

ORD 기록
ord-2597a562c507424a87e94c6f68fd807e
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946237B2

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