Sodium Cyanide → 3-cyanopropyl 2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate

HRID 870587Notes

Reaction equation

HRID 870587 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[NH:10][C:11]1[N:12]=[CH:13][C:14]2[CH2:20][N:19]([C:21]([O:23][CH2:24][CH2:25][CH2:26]Cl)=[O:22])[CH2:18][CH2:17][C:15]=2[N:16]=1.[C-:28]#[N:29].[Na+]>CN(C)C=O.ClCCl>[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[NH:10][C:11]1[N:12]=[CH:13][C:14]2[CH2:20][N:19]([C:21]([O:23][CH2:24][CH2:25][CH2:26][C:28]#[N:29])=[O:22])[CH2:18][CH2:17][C:15]=2[N:16]=1

Participants

5

Reactant 2

HCID 8929Sodium CyanideHCID 86726549HCID 86726549, compound

Product 1

HCID 867265503-cyanopropyl 2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Heat a solution of 3-chloropropyl 2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylate (0.42 g; 1.0 equiv; 1.09 mmoles) and and sodium cyanide (0.085 g; 1.6 equiv; 1.73 mmoles) in dimethylformamide (3 mL) to 100° C. for 2 hours. Cool the mixture to ambient temperature, dilute with dichloromethane (20 mL) and wash the reaction mixture with water (25 mL). Extract the aqueous layer with dichloromethane (2×20 mL). Dry the combined organic extracts over sodium sulfate, filter, and concentrate to afford crude product. Combine the crude product and purify by column chromatography (0 to 10% methanol in dichloromethane) to afford 3-cyanopropyl 2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate as a light brown oil and used in next step. MS (m/z): 378 (M+1).

Workup

  1. washwash the reaction mixture with water (25 mL)
  2. extractionExtract the aqueous layer with dichloromethane (2×20 mL)
  3. dry with materialDry the combined organic extracts over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customto afford crude product
  7. custompurify by column chromatography (0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-41922409a17e4de6bc19719c06b516c2
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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