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

Reaction equation

HRID 242326 reaction equation
[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

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×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

Product 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}-methanoneYield 85.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-2abaa305b3ea4a47807bad42bbb55357
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Linked notes

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