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Cesium carbonate → tert-butyl (2R,3R)-1-(5-cyano-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate

HRID 1050561
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HRID 1050561 반응식
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C@H:9]2[CH3:22])[CH:5]=[N:4][C:3]=1[C:23]#[N:24].Cl.[CH:26]1([N:31]2[CH2:36][CH2:35][CH:34]([C:37]3[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=3)[CH2:33][CH2:32]2)[CH2:30][CH2:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:23]([C:3]1[N:4]=[CH:5][C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C@H:9]2[CH3:22])=[N:7][C:2]=1[NH:41][C:40]1[CH:42]=[CH:43][C:37]([CH:34]2[CH2:35][CH2:36][N:31]([CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:32][CH2:33]2)=[CH:38][CH:39]=1)#[N:24]
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8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 1181146604-(1-Cyclopentylpiperidin-4-yl)aniline hydrochlorideHCID 118136131tert-butyl (2R,3R)-1-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate

생성물 1

HCID 118136128tert-butyl (2R,3R)-1-(5-cyano-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate
수율 68%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
115 °C

실험 절차

tert-Butyl (2R,3R)-1-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (311) (390 mg, 1.1 mmol), 4-(1-cyclopentylpiperidin-4-yl)aniline HCl salt (304) (406 mg, 1.7 mmol), fine-powder Cs2CO3 (1.1 g, 3.3 mmol), BINAP (207 mg, 0.33 mmol), and Pd(OAc)2 (75 mg, 0.33 mmol) were combined and suspended in dioxane (30 mL) and water (1 mL). The mixture was sparged with nitrogen stream for 10 minutes, and then stirred under nitrogen atmosphere in 115° C. oil bath for 5 hours. The mixture was cooled to RT, diluted with EtOAc (100 mL), stirred, filtered and concentrated under reduced pressure. The resulting residue was subjected to silica flash column chromatography (MeOH/DCM) to give tert-butyl (2R,3R)-1-(5-cyano-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (312) (430 mg, 0.74 mmol, 68% yield).

후처리

  1. customThe mixture was sparged with nitrogen stream for 10 minutes
  2. temperatureThe mixture was cooled to RT
  3. additiondiluted with EtOAc (100 mL)
  4. stirringstirred
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-20d78b71306b4b1b9720c8765249679e
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09382246B2

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