Triethylamine → [(S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidin-1-yl]-(tetrahydro-pyran-4-yl)-methanone

HRID 242333Notes

Reaction equation

HRID 242333 reaction equation
[CH2:1]([N:8]1[CH2:23][CH2:22][C:11]2[N:12]=[CH:13][N:14]=[C:15]([O:16][C@H:17]3[CH2:21][CH2:20][NH:19][CH2:18]3)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:24]1[CH2:29][CH2:28][CH:27]([C:30](Cl)=[O:31])[CH2:26][CH2:25]1.CCN(CC)CC>C(Cl)Cl>[CH2:1]([N:8]1[CH2:23][CH2:22][C:11]2[N:12]=[CH:13][N:14]=[C:15]([O:16][C@H:17]3[CH2:21][CH2:20][N:19]([C:30]([CH:27]4[CH2:28][CH2:29][O:24][CH2:25][CH2:26]4)=[O:31])[CH2:18]3)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2795505Oxane-4-carbonyl chlorideHCID 574953476-benzyl-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

Product 1

HCID 57495346[(S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidin-1-yl]-(tetrahydro-pyran-4-yl)-methanoneYield 73.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-benzyl-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (420 mg, 1.35 mmol) in 4 mL of CH2Cl2 was added tetrahydro-pyran-4-carbonyl chloride (0.210 mL, 1.637 mmol) and Et3N (0.380 mL, 2.73 mmol). The reaction mixture was stirred at room temperature for 30 min then was quenched with H2O, extracted with CH2Cl2, filtered and evaporated under vacuum. Purification by flash-chromatography on silica gel (CH2Cl2/MeOH 95/5) gave [(S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidin-1-yl]-(tetrahydro-pyran-4-yl)-methanone (420 mg, 73% yield) as a yellow foam. 1H NMR (400 MHz, DMSO-d6, 298K) δ ppm 1.37-1.64 (m, 4H) 1.95-2.29 (m, 2H) 2.56-2.83 (m, 4H) 3.28-3.91 (m, 13H) 5.54-5.68 (m, 1H) 7.24-7.36 (m, 5H) 8.54-8.59 (m, 1H). LCMS: [M+H]+=423.6, Rt(7)=0.68.

Workup

  1. customthen was quenched with H2O
  2. extractionextracted with CH2Cl2
  3. filtrationfiltered
  4. customevaporated under vacuum
  5. customPurification by flash-chromatography on silica gel (CH2Cl2/MeOH 95/5)

Sources & evidence

ORD record
ord-db2e35cd215a4004bb752b0c8686aaec
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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