1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (5-Benzyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-(4,6-dimethyl-pyrimidin-5-yl)-methanone

HRID 1374474노트

반응식

HRID 1374474 반응식
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([CH3:11])[N:5]=[CH:4][N:3]=1.[CH2:12]([N:19]1[CH2:26][CH:25]2[CH:21]([CH2:22][NH:23][CH2:24]2)[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:12]([N:19]1[CH2:26][CH:25]2[CH2:24][N:23]([C:8]([C:7]3[C:2]([CH3:1])=[N:3][CH:4]=[N:5][C:6]=3[CH3:11])=[O:10])[CH2:22][CH:21]2[CH2:20]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

참가 물질

7

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 44543872-Benzyloctahydropyrrolo[3,4-c]pyrroleHCID 149222224,6-Dimethylpyrimidine-5-carboxylic acid

생성물 1

HCID 21076218(5-Benzyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-(4,6-dimethyl-pyrimidin-5-yl)-methanone수율 79.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

step 1—To a mixture of 4,6-dimethyl-pyrimidine-5-carboxylic acid (0.85 g, 5.58 mmol, T. J. Kress et. al. Heterocycles 1994 38:1375) and 4a (1.13 g, 5.58 mmol, C. J. Ohnmacht et al. J. Heterocycl. Chem. 1983 20:321) in DCM (25 mL) at RT was added sequentially EDCI (1.43 g, 6.7 mmol), HOBt (0.9 g, 6.7 mmol) and DIPEA (3.9 mL, 22.34 mmol) and the mixture was stirred overnight at RT. The reaction mixture was washed with 5% NaHCO3 solution, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4%) to afford 1.5 g of (5-benzyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-(4,6-dimethyl-pyrimidin-5-yl)-methanone: ms (ES+) m/z 337 (M+H)+. To a solution of amide from the previous step (1.5 g, 4.45 mmol) in MeOH (50 mL) was added ammonium formate (2.81 g, 44.58 mmol). Palladium on charcoal previously wetted with MeOH was slowly added and the mixture heated to reflux for 8 h. The catalyst was filtered and solvent evaporated. The residue was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4%) to afford 0.941 g of 44b: ms (ES+) m/z 247 (M+H)+.

후처리

  1. washThe reaction mixture was washed with 5% NaHCO3 solution
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography on silica gel eluting with MeOH (containing 10% NH4OH)/DCM (0 to 4%)

출처 및 근거

ORD 기록
ord-3ea4a9f9d6f3465cbe1c7a828445100d
출처 데이터셋
uspto-grants-2007_01
특허 번호
US07164019B2

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