Imidazole → 3-(1H-imidazol-1-yl)propyl 2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate

HRID 870586Notes

Reaction equation

HRID 870586 reaction equation
[H-].[Na+].[CH2:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH:4]1[NH:12][C:13]1[N:14]=[CH:15][C:16]2[CH2:22][N:21]([C:23]([O:25][CH2:26][CH2:27][CH2:28]Cl)=[O:24])[CH2:20][CH2:19][C:17]=2[N:18]=1.[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.ClCCl>CN(C)C=O.O>[CH2:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH:4]1[NH:12][C:13]1[N:14]=[CH:15][C:16]2[CH2:22][N:21]([C:23]([O:25][CH2:26][CH2:27][CH2:28][N:30]3[CH:34]=[CH:33][N:32]=[CH:31]3)=[O:24])[CH2:20][CH2:19][C:17]=2[N:18]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 86726549HCID 86726549, compound

Product 1

HCID 867265483-(1H-imidazol-1-yl)propyl 2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylateYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Add sodium hydride (0.050 g; 2.2 equiv; 1.25 mmoles) to a solution of 3-chloropropyl 2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylate (0.22 g; 1.0 equiv; 0.57 mmoles) and 1H-imidazole (0.082 g; 2.1 equiv; 1.20 mmoles) in dimethylformamide (2 mL) and stir for 18 hours. Dilute the reaction with dichloromethane and water. Separate the layers and further extract the aqueous layer with dichloromethane (2×). Dry the combined organic extracts with sodium sulfate, filter, and concentrate. Purify the crude product by column chromatography (0 to 10% methanol in dichloromethane) to afford the desired 3-(1H-imidazol-1-yl)propyl 2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (0.078 g; 33%) as a white solid: MS (m/z): 419 (M+1).

Workup

  1. additionDilute
  2. customSeparate the layers
  3. extractionfurther extract the aqueous layer with dichloromethane (2×)
  4. dry with materialDry the combined organic extracts with sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude product by column chromatography (0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-5bef58dad4b14bb5a48e406214e1daa9
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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