Methanol → tert-butyl 3-{[1-(3-benzyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]amino}propylcarbamate

HRID 1784477Notes

Reaction equation

HRID 1784477 reaction equation
CS(O[CH:6]([C:9]1[N:10]=[C:11]2[CH2:26][CH2:25][CH2:24][CH2:23][N:12]2[C:13](=[O:22])[C:14]=1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:7][CH3:8])(=O)=O.[NH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35].[I-].[K+].CO>CN(C=O)C.C(Cl)Cl>[NH3:10].[CH2:15]([C:14]1[C:13](=[O:22])[N:12]2[CH2:23][CH2:24][CH2:25][CH2:26][C:11]2=[N:10][C:9]=1[CH:6]([NH:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:7][CH3:8])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 4875Potassium IodideHCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 575932061-(3-benzyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl methanesulfonate

Product 2

HCID 222AmmoniaYield 0.1%HCID 57593203tert-butyl 3-{[1-(3-benzyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]amino}propylcarbamateYield 28.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 0.106 g (0.28 mmol) of the product from Step 9 (25), 0.15 g (0.84 mmol) of tert-butyl 3-aminopropylcarbamate, and 0.005 g (0.03 mmol) of potassium iodide in 5 mL of DMF was stirred at 60° C. under nitrogen for 24 hours. The reaction was quenched with water, extracted with ethyl acetate (4×) and the combined organic layers were washed with saturated NaHCO3 and brine and dried over MgSO4. The solvent was removed in vacuo and the crude reaction mixture was subjected to flash chromatography on a 7 cm column. Elution with a gradient of 50% ethyl acetate in hexanes, 100% ethyl acetate, 3% methanol and 0.1% ammonia in DCM, and 10% methanol and 0.1% ammonia in DCM yielded 0.019 g (0.04 mmol, 15%) of tert-butyl 3-{[1-(3-benzyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]amino}propylcarbamate (26) as a clear oil.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate (4×)
  3. washthe combined organic layers were washed with saturated NaHCO3 and brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed in vacuo
  6. customthe crude reaction mixture
  7. washElution with a gradient of 50% ethyl acetate in hexanes, 100% ethyl acetate, 3% methanol and 0.1% ammonia in DCM

Sources & evidence

ORD record
ord-42dac9e0cc2e438baefdc9be2c640253
Source dataset
uspto-grants-2009_03
Patent number
US07504405B2

Reaction notes

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