Sodium Acetate → (2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-{1-methyl-5-[(1-methyl-5-{[methyl(oxetan-3-yl)amino]methyl}-1H-pyrazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}phenyl)methyl Acetate

HRID 1919119노트

반응식

HRID 1919119 반응식
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH2:16][N:17]([CH3:22])[CH:18]3[CH2:21][O:20][CH2:19]3)[N:13]([CH3:23])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:24]([O:27][CH2:28][C:29]1[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][C:32]([F:44])=[CH:31][C:30]=1[N:45]1[CH2:56][CH2:55][C:54]2[C:53]3[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50][C:49]=3[S:48][C:47]=2[C:46]1=[O:59])(=[O:26])[CH3:25].CC([O-])=O.[Na+]>CC#N.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:24]([O:27][CH2:28][C:29]1[C:34]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:15]=[C:14]([CH2:16][N:17]([CH3:22])[CH:18]4[CH2:21][O:20][CH2:19]4)[N:13]([CH3:23])[N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)=[CH:33][C:32]([F:44])=[CH:31][C:30]=1[N:45]1[CH2:56][CH2:55][C:54]2[C:53]3[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50][C:49]=3[S:48][C:47]=2[C:46]1=[O:59])(=[O:26])[CH3:25]

참가 물질

6

반응물 3

HCID 517045Sodium AcetateHCID 580437865-Bromo-1-methyl-3-(1-methyl-5-((methyl(oxetan-3-yl)amino)methyl)-1H-pyrazol-3-ylamino)pyridin-2(1H)-oneHCID 67016224(2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl Acetate

생성물 1

HCID 58043683(2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-{1-methyl-5-[(1-methyl-5-{[methyl(oxetan-3-yl)amino]methyl}-1H-pyrazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}phenyl)methyl Acetate수율 67%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6342Acetonitrile용매

반응 조건

온도
110 °C

실험 절차

A sealed tube was charged with the mixture of 5-bromo-1-methyl-3-(1-methyl-5-((methyl(oxetan-3-yl)amino)methyl)-1H-pyrazol-3-ylamino)pyridin-2(1H)-one 320d (250 mg, 0.65 mmol), (2-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 247b (334 mg, 0.65 mmol), Pd(dppf)Cl2 (55 mg, 0.07 mmol), K3PO4.3H2O(345 mg, 1.3 mmol), and NaOAc (105 mg, 1.3 mmol) in CH3CN (20 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 110° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography eluting with 30:1 methylene chloride/methanol to afford 322a as a yellow solid (300 mg, 56%). MS: [M+H]+ 689.

후처리

  1. customThe system was evacuated
  2. additionrefilled with N2
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by flash column chromatography
  7. washeluting with 30:1 methylene chloride/methanol

출처 및 근거

ORD 기록
ord-df2cbe957f2a4571888faaf9c8c64eca
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618107B2

반응 노트

불러오는 중…