Cesium carbonate → (R)-3-methyl-2-(5-(5-((2-(pyrrolidin-1-yl)ethoxy)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide

HRID 510214노트

반응식

HRID 510214 반응식
Cl[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]([NH:17][C@H:18]([CH:27]([CH3:29])[CH3:28])[C:19]([NH:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[O:20])[CH:14]=[N:15][CH:16]=3)=[CH:9][N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:5]2=[N:6][CH:7]=1.ClC1C=C2C(C3C=C(N[C@H](C(NCC(F)(F)F)=O)C(C)C)C=NC=3)=CN(COCC[Si](C)(C)C)C2=NC=1.[N:75]1([CH2:80][CH2:81][O:82][CH2:83][B-](F)(F)F)[CH2:79][CH2:78][CH2:77][CH2:76]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCOCC1>[CH3:28][CH:27]([CH3:29])[C@@H:18]([NH:17][C:13]1[CH:14]=[N:15][CH:16]=[C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([CH2:83][O:82][CH2:81][CH2:80][N:75]4[CH2:79][CH2:78][CH2:77][CH2:76]4)[CH:3]=3)[N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=2)[CH:12]=1)[C:19]([NH:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[O:20]

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 49761739Potassium 2-(pyrrolidin-1-YL)ethoxymethyltrifluoroborateHCID 131733258N2-[5-(5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamideHCID 131733263(R)-2-(5-(5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide

생성물 1

HCID 89495580(R)-3-methyl-2-(5-(5-((2-(pyrrolidin-1-yl)ethoxy)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
150 °C

실험 절차

In a microwave vial purged with nitrogen containing (R)-2-(5-(5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide, 2-1a (52 mg, 0.094 mmol), Potassium 2-(pyrrolidin-1-yl)ethoxymethyltrifluoroborate (CA) (44.4 mg, 0.189 mmol), cesium carbonate (105.3 mg, 0.323 mmol), palladium acetate (4.2 mg, 0.019 mmole) and RuPhos catalyst (17.45 mg, 0.037 mmol) was added a degassed mixture of 10:1 dioxane (500 μl)/water (50 μl). The reaction vessel was sealed and heated at 150° C. for 15 minutes in the microwave. LC/MS indicated product as a major peak. The reaction was cooled, passed through a celite cartridge, to remove water, the cartridge was washed with dichloromethane, ethyl acetate and the filtrate concentrated. The crude product 9-1a (60.7 mg) was used directly in the next step. LRMS (ESI) m/z 649.2 [(M+H)+; calcd for C32H47F3N6O3Si: 649.35].

후처리

  1. customIn a microwave vial purged with nitrogen
  2. additionwas added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction was cooled
  5. customto remove water
  6. washthe cartridge was washed with dichloromethane, ethyl acetate
  7. concentrationthe filtrate concentrated

출처 및 근거

ORD 기록
ord-87726d65836a49068d00898342b7b367
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096598B2

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