4-Methylmorpholine → 2-(6-Bromo-isoquinolin-1-yl carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71729

반응식

HRID 71729 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([NH2:12])=[N:7][CH:6]=[CH:5]2.[C:13]([N:20]1[CH2:27][CH2:26][CH2:25][C@H:21]1[C:22](O)=[O:23])([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:16]([O:15][C:13]([N:20]1[CH2:27][CH2:26][CH2:25][CH:21]1[C:22](=[O:23])[NH:12][C:8]1[C:9]2[C:4](=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][N:7]=1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

참가 물질

6

반응물 4

HCID 79724-Methylmorpholine2회HCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2회HCID 226076161-Amino-6-bromoisoquinoline

생성물 1

HCID 666205232-(6-Bromo-isoquinolin-1-yl carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester수율 115.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 6-Bromo-isoquinolin-1-ylamine (0.80 g), Boc-L-proline (0.803 g), and 4-methylmorpholine (0.83 mL) in DMF (10 mL) was added HATU (1.39 g). Reaction mixture was stirred for 6 hours. Additional Boc-L-proline (0.803 g), 4-methylmorpholine (0.83 mL) and HATU (1.39 g) were added and reaction stirred overnight at ambient temperature and then concentrated. The residue was dissolved in ethyl acetate and washed with 10:1 H2O/saturated sodium bicarbonate solution, 5% lithium chloride solution, brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 70% ethyl acetate/hexanes) to give 2-(6-Bromo-isoquinolin-1-yl carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.74 g): LCMS-ESI+: calc'd for C19H23BrN3O3: 421.31 (M+H+). Found: 419.8, 421.8 (M+H+).

후처리

  1. customReaction mixture
  2. customreaction
  3. stirringstirred overnight at ambient temperature
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washwashed with 10:1 H2O/saturated sodium bicarbonate solution, 5% lithium chloride solution, brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. custompurified by flash column chromatography (silica gel, 20 to 70% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-131b828668184cd4aa33d7fb88522739
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822430B2

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