Triethylamine → 1-Pyrrolidinecarboxylic acid, 3-[[5,6,7,8-tetrahydro-6-(phenylmethyl)pyrido[4,3-d]pyrimidin-4-yl]amino]-, 1,1-dimethylethyl ester, (3S)-

HRID 242315

반응식

HRID 242315 반응식
[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15](Cl)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:19][C@H:20]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21]1.C(N(CC)CC)C>COC(C)(C)C.O>[C:28]([O:27][C:25]([N:22]1[CH2:23][CH2:24][C@H:20]([NH:19][C:15]2[C:10]3[CH2:9][N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:18][CH2:17][C:11]=3[N:12]=[CH:13][N:14]=2)[CH2:21]1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 253240466-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidine

생성물 1

HCID 574953231-Pyrrolidinecarboxylic acid, 3-[[5,6,7,8-tetrahydro-6-(phenylmethyl)pyrido[4,3-d]pyrimidin-4-yl]amino]-, 1,1-dimethylethyl ester, (3S)-수율 94.3%

시약·촉매·용매 2

HCID 962Water용매HCID 15413tert-Butyl methyl ether용매

실험 절차

6-Benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (5.0 g, 19.06 mmol), (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (4.11 g, 20.96 g) and triethylamine (3.98 mL, 28.6 mmol) were heated in a sealed vial at 120° C. for 42 h. The mixture was allowed to cool, diluted with tert-butyl methyl ether (100 mL) and the resulting suspension stirred for 10 min. The mixture was diluted with water (50 mL) and the organic layer separated. The organic layer was washed with brine (20 mL), dried (Na2SO4) and evaporated in vacuo to give a brown gum. The residue was purified by column chromatography on silica gel with EtOAc/MeOH, 98/2 to 82/18 to give (S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester as a pale yellow foam (7.36 g, 93% yield). 1H-NMR (400 MHz, CDCl3, 298 K): δ ppm 1.48 (s, 9H) 2.10-2.31 (m, 2H) 2.80-2.96 (m, 4H) 3.15-3.87 (m, 8H) 4.44-4.77 (m, 1H) 5.62-5.73 (m, 1H) 7.29-7.45 (m, 5H) 8.50 (s, 1H). LCMS: [M+H]+=410.0, Rt(6)=1.39 min.

후처리

  1. temperatureto cool
  2. customthe organic layer separated
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customto give a brown gum
  7. customThe residue was purified by column chromatography on silica gel with EtOAc/MeOH, 98/2 to 82/18

출처 및 근거

ORD 기록
ord-f4dc2b65219f46c0bfeb4b91f308a561
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653092B2

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