Diisopropylethylamine → (2,4-dimethyl-oxazol-5-yl)-{(S)-3-[6-(6-methoxy-5-methyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidin-1-yl}-methanone

HRID 242326

反応式

HRID 242326 の反応式
[CH3:1][C:2]1[O:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.CCN(C(C)C)C(C)C.[CH3:20][O:21][C:22]1[N:27]=[CH:26][C:25]([N:28]2[CH2:43][CH2:42][C:31]3[N:32]=[CH:33][N:34]=[C:35]([O:36][C@H:37]4[CH2:41][CH2:40][NH:39][CH2:38]4)[C:30]=3[CH2:29]2)=[CH:24][C:23]=1[CH3:44]>CN(C=O)C>[CH3:1][C:2]1[O:3][C:4]([C:8]([N:39]2[CH2:40][CH2:41][C@H:37]([O:36][C:35]3[C:30]4[CH2:29][N:28]([C:25]5[CH:26]=[N:27][C:22]([O:21][CH3:20])=[C:23]([CH3:44])[CH:24]=5)[CH2:43][CH2:42][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:38]2)=[O:10])=[C:5]([CH3:7])[N:6]=1

参加物

5

反応物 3

HCID 81531Diisopropylethylamine2 回HCID 1132979Dimethyl-1,3-oxazole-5-carboxylic acidHCID 574953306-(6-methoxy-5-methyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

生成物 1

HCID 56651216(2,4-dimethyl-oxazol-5-yl)-{(S)-3-[6-(6-methoxy-5-methyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidin-1-yl}-methanone収率 85.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

A mixture of 2,4-dimethyl-oxazole-5-carboxylic acid (36.4 mg, 0.258 mmol), HTBU (98 mg, 0.258 mmol), DIPEA (86p1, 0.49 mmol) in DMF (5 mL) was stirred at rt for 20 min. then a solution of 6-(6-methoxy-5-methyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (prepared in example 1, method 1b, step 2) (80 mg, 0.23 mmol) and DIPEA (86 μl, 0.49 mmol) in DMF (0.4 mL) was added. The reaction mixture was stirred 30 min at rt. The reaction mixture was directly purified by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HCO3 MP gave (2,4-dimethyl-oxazol-5-yl)-{(S)-3-[6-(6-methoxy-5-methyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidin-1-yl}-methanone (91 mg, 84% yield) as a white lyophilized powder. 1H-NMR (400 MHz, methanol-d4, 298K) δ ppm 2.17 (s, 3H) 2.27-2.52 (m, 8H) 2.95-3.03 (m, 2H) 3.44-3.55 (m, 2H) 3.70-4.26 (m, 9H) 5.76-5.92 (m, 1H) 7.40 (br. s., 1H) 7.64 (br. s., 1H) 8.55-8.62 (m, 1H), LCMS: [M+H]+=465.2, Rt(1)=1.51 min.

後処理

  1. stirringThe reaction mixture was stirred 30 min at rt
  2. customThe reaction mixture was directly purified by preparative reverse phase Gilson HPLC and subsequent neutralization of the combined fractions over PL-HCO3 MP

出典と根拠

ORDレコード
ord-2abaa305b3ea4a47807bad42bbb55357
出典データセット
uspto-grants-2014_02
特許番号
US08653092B2

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