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

反応式

HRID 242315 の反応式
[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]

参加物

6

反応物 3

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

生成物 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)-収率 94.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 15413tert-Butyl methyl ether溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f4dc2b65219f46c0bfeb4b91f308a561
出典データセット
uspto-grants-2014_02
特許番号
US08653092B2

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