Dimethylamine, hydrochloride → 4-[[3-(3-Butyn-1-yl)-3,5,7,8-tetrahydro-4-oxo-2-[[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]amino]pyrido[4,3-d]pyrimidin-6(4H)-yl]carbonyl]-N,N-dimethylbenzamide

HRID 1500615Notes

Reaction equation

HRID 1500615 reaction equation
CO[C:3](=[O:40])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:39][CH2:38][C:15]3[N:16]=[C:17]([NH:25][C@H:26]([C:28]4[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=4)[CH3:27])[N:18]([CH2:21][CH2:22][C:23]#[CH:24])[C:19](=[O:20])[C:14]=3[CH2:13]2)=[O:11])=[CH:6][CH:5]=1.[OH-].[Na+].[Cl-].[NH4+].C1C=CC2N(O)N=NC=2C=1.C[CH2:56][N:57]=[C:58]=NCCCN(C)C.Cl.CNC>CO.C(Cl)Cl.C(N(CC)CC)C>[CH2:21]([N:18]1[C:19](=[O:20])[C:14]2[CH2:13][N:12]([C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:3]([N:57]([CH3:58])[CH3:56])=[O:40])=[CH:5][CH:6]=3)=[O:11])[CH2:39][CH2:38][C:15]=2[N:16]=[C:17]1[NH:25][C@H:26]([C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:30][CH:29]=1)[CH3:27])[CH2:22][C:23]#[CH:24]

Participants

10

Reactant 6

HCID 10473Dimethylamine, hydrochlorideHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 123583625HCID 123583625, compound

Product 1

HCID 911794144-[[3-(3-Butyn-1-yl)-3,5,7,8-tetrahydro-4-oxo-2-[[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]amino]pyrido[4,3-d]pyrimidin-6(4H)-yl]carbonyl]-N,N-dimethylbenzamideYield 65.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

4-{3-(3-Butynyl)-4-oxo-2-[(S)-1-(4-trifluoromethylphenyl)ethylamino]-3,5,7,8-tetrahydro-4H-pyrido[4,3-d]pyrimidine-6-carbonyl}benzoic acid methyl ester (360 mg) was dissolved in MeOH (6 ml), and 5N NaOH solution (0.65 ml) was added. The reaction mixture was stirred at room temperature for 20 hr. The reaction mixture was acidified with aqueous ammonium chloride. The mixture was extracted with methylene chloride and ethyl acetate successively, and the organic layer was dried over sodium sulfate. The organic layer was filtrated and concentrated under reduced pressure to afford the crude acid (0.40 g). The crude acid was suspended in methylene chloride (12 ml), and to the suspension HOBT (0.15 g), WSC (0.19 g), dimethylamine hydrochloride (0.11 g) and triethylamine (0.18 ml) were added. The reaction mixture was stirred at room temperature for 12 hr. The reaction solution was quenched with aqueous NaHCO3, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified medium-pressure silica gel column chromatography (solvent; ethyl acetate:hexane=2:3 to 0:100). The titled compound (0.24 g) was obtained as a colorless amorphous substance.

Workup

  1. extractionThe mixture was extracted with methylene chloride and ethyl acetate successively
  2. dry with materialthe organic layer was dried over sodium sulfate
  3. filtrationThe organic layer was filtrated
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude acid (0.40 g)
  6. stirringThe reaction mixture was stirred at room temperature for 12 hr
  7. customThe reaction solution was quenched with aqueous NaHCO3
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified medium-pressure silica gel column chromatography (solvent; ethyl acetate:hexane=2:3 to 0:100)

Sources & evidence

ORD record
ord-b011f6934ac24ac8a415ceced316ff27
Source dataset
uspto-grants-2015_12
Patent number
US09206173B2

Reaction notes

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