(S)-3-[6-(6-Methoxy-5-methyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester → 6-(6-methoxy-5-methyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

HRID 242324Notes

Reaction equation

HRID 242324 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[C:15]3[CH2:23][N:22]([C:24]4[CH:25]=[N:26][C:27]([O:31][CH3:32])=[C:28]([CH3:30])[CH:29]=4)[CH2:21][CH2:20][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:9]1)=O)(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH3:32][O:31][C:27]1[N:26]=[CH:25][C:24]([N:22]2[CH2:21][CH2:20][C:16]3[N:17]=[CH:18][N:19]=[C:14]([O:13][C@H:10]4[CH2:11][CH2:12][NH:8][CH2:9]4)[C:15]=3[CH2:23]2)=[CH:29][C:28]=1[CH3:30]

Participants

3

Reactant 1

HCID 57495331(S)-3-[6-(6-Methoxy-5-methyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 574953306-(6-methoxy-5-methyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

(S)-3-[6-(6-Methoxy-5-methyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester (2.05 g, 4.63 mmol) was dissolved in TFA/CH2Cl2 (1/2) and stirred at rt for 1 h. The reaction mixture was concentrated under vacuum, the residue was diluted with CH2Cl2, the organic layer washed with NaOH 1N then brine, dried over Na2SO4, filtered and evaporated to give 6-(6-methoxy-5-methyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, CDCl3, 298K) δ ppm 2.20-2.30 (m, 2 H), 2.22 (s, 3 H), 3.00-3.06 (t, 2 H), 3.09-3.18 (m, 1 H), 3.22-3.37 (m, 3 H), 3.45-3.50 (t, 2 H), 3.95 (s 3 H), 4.10 (s, 2 H), 4.20-4.65 (br.s 1 H), 5.63-5.69 (m, 1 H), 7.21-7.252 (m, 1 H), 7.70-7.74 (m, 1 H), 8.60 (s, 1 H). LCMS: [M+H]+=341.9, Rt(7)=0.61 min.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. additionthe residue was diluted with CH2Cl2
  3. washthe organic layer washed with NaOH 1N
  4. dry with materialbrine, dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-3e29dd5145494ce4835de46c24ad57f3
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

Loading…