Dichloromethane → 5-(5-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-(2-(dimethylamino)ethyl)thiophene-2-sulfonamide

HRID 1484921노트

반응식

HRID 1484921 반응식
C(Cl)Cl.[CH3:4][N:5]([CH3:26])[CH2:6][CH2:7][NH:8][S:9]([C:12]1[S:13][C:14](B2OC(C)(C)C(C)(C)O2)=[CH:15][CH:16]=1)(=[O:11])=[O:10].Br[C:28]1[N:33]=[C:32]([NH:34][C:35]2[CH:39]=[C:38]([CH:40]3[CH2:42][CH2:41]3)[NH:37][N:36]=2)[C:31]([Br:43])=[CH:30][N:29]=1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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]>[Br:43][C:31]1[C:32]([NH:34][C:35]2[CH:39]=[C:38]([CH:40]3[CH2:42][CH2:41]3)[NH:37][N:36]=2)=[N:33][C:28]([C:14]2[S:13][C:12]([S:9]([NH:8][CH2:7][CH2:6][N:5]([CH3:4])[CH3:26])(=[O:10])=[O:11])=[CH:16][CH:15]=2)=[N:29][CH:30]=1

참가 물질

7

반응물 3

HCID 6344DichloromethaneHCID 581691912,5-dibromo-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amineHCID 66927474N-(2-(dimethyl amino)ethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-sulfonamide

생성물 1

HCID 581695025-(5-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-(2-(dimethylamino)ethyl)thiophene-2-sulfonamide수율 20%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 10340Sodium Carbonate용매HCID 312751,4-Dioxane용매

실험 절차

A mixture of Pd(dppf)Cl2.CH2Cl2 (182 mg, 0.22 mmol, 0.1 equiv.), the crude N-(2-(dimethyl amino)ethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-sulfonamide and 2,5-dibromo-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (700 mg, 1.95 mmol, 1.0 eq) in dioxane (20 mL) and saturated Na2CO3 aqueous (2 mL) was heated at 100° C. for 2 h under nitrogen atmosphere. The reaction mixture was cooled to room temperature, and extracted with THF. The combined organic layers were purified by silica gel chromatography to afford compound 5-(5-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-(2-(dimethylamino)ethyl)thiophene-2-sulfonamide (200 mg, 20% over 2 steps). LC-MS (m/z)=512.0, 514.0 [M+H]+.

후처리

  1. extractionextracted with THF
  2. customThe combined organic layers were purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-018d8829acaf4c8e8ef5ed5e56c5a5f8
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422271B2

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