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 1500615노트

반응식

HRID 1500615 반응식
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]

참가 물질

10

반응물 6

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

생성물 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-dimethylbenzamide수율 65.1%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b011f6934ac24ac8a415ceced316ff27
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206173B2

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