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 510214ノート

反応式

HRID 510214 の反応式
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]

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

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].

後処理

  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

出典と根拠

ORDレコード
ord-87726d65836a49068d00898342b7b367
出典データセット
uspto-grants-2015_08
特許番号
US09096598B2

反応ノート

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