Cesium carbonate → tert-Butyl 3-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate

HRID 592387노트

반응식

HRID 592387 반응식
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:29][C:30]1[CH:31]=[N:32][N:33]([CH:35]2[CH2:38][N:37]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:36]2)[CH:34]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1>[C:19]([C:16]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:6]2[C:5]([Cl:22])=[CH:4][N:3]=[C:2]([NH:29][C:30]3[CH:31]=[N:32][N:33]([CH:35]4[CH2:38][N:37]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:36]4)[CH:34]=3)[N:7]=2)[CH2:18][CH2:17]1)(=[O:20])[NH2:21]

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 272815264-Amino-1-(1-Boc-azetidin-3-yl)-1H-pyrazoleHCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

생성물 1

HCID 86712299tert-Butyl 3-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.100 g, 0.297 mmol), Cs2CO3 (0.291 g, 0.892 mmol) and tert-butyl 3-(4-amino-1H-pyrazol-1-yl)azetidine-1-carboxylate (0.142 g, 0.595 mmol) in dioxane (3 mL) was sonicated for 10 minutes. Xantphos (6.9 mg, 12 μmol) and Pd(II) acetate (1.3 mg, 5.9 μmol) were added to the suspension and the mixture was irradiated in the microwave for 20 minutes at 120° C. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-40% MeOH in EtOAc) to give the title compound A18 as a yellow oil (110 mg, 69%). LCMS-A: rt 6.349 min; m/z 538.3 [M+H]+.

후처리

  1. customwas sonicated for 10 minutes
  2. customthe mixture was irradiated in the microwave for 20 minutes at 120° C
  3. custompurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

출처 및 근거

ORD 기록
ord-d3880b2776414954bc7edb3618357c68
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238644B2

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