Cesium fluoride → HCID 178462223, 화합물

HRID 1406318노트

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HRID 1406318 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]([OH:15])=[N:13][CH:14]=2)O1.Br[C:18]1[CH:19]=[C:20]([O:25][C@@H:26]([C:28]2[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=2[N:35]2[N:39]=[CH:38][CH:37]=[N:36]2)[CH3:27])[C:21]([NH2:24])=[N:22][CH:23]=1.[F-].[Cs+].B([O-])[O-]>CO.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]>[NH2:24][C:21]1[N:22]=[CH:23][C:18]([C:9]2[CH:14]=[N:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:19][C:20]=1[O:25][C@@H:26]([C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[N:35]1[N:39]=[CH:38][CH:37]=[N:36]1)[CH3:27]

참가 물질

7

반응물 4

HCID 25953Cesium fluorideHCID 67468125(R)-5-bromo-3-(1-(5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)ethoxy)pyridin-2-amineHCID 178431084HCID 178431084, 화합물HCID 178514824HCID 178514824, 화합물

생성물 1

HCID 178462223HCID 178462223, 화합물

시약·촉매·용매 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 887Methanol용매

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온도
120 °C

실험 절차

A mixture of the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-ol (470 mg, 2.13 mmol), (R)-5-bromo-3-(1-(5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)ethoxy)pyridin-2-amine of preparation 45 (510 mg, 1.35 mmol) and CsF (724 mg, 4.72 mmol) were taken up in MeOH (13 mL). The mixture was thoroughly degassed before Pd(dppf)Cl2 (55 mg, 0.067 mmol) was added and the mixture was heated in the microwave at 120° C. for 2 hr. LCMS showed the presence of starting materials. Additional portions of Pd(dppf)Cl2 (27 mg) and boronate (100 mg) were added. The mixture was degassed again and heated in the microwave at 120° C. for another 1 hr. LCMS indicated the complete consumption of bromide starting material. The mixture was filtered and the filtrate was concentrated. The residue was taken up in MeOH and purified by a reverse phase prep-HPLC to give the title compound (115 mg) as a fluffy white solid after lyophilization.

후처리

  1. additionwas added
  2. customThe mixture was degassed again
  3. temperatureheated in the microwave at 120° C. for another 1 hr
  4. customthe complete consumption of bromide starting material
  5. filtrationThe mixture was filtered
  6. concentrationthe filtrate was concentrated
  7. custompurified by a reverse phase prep-HPLC

출처 및 근거

ORD 기록
ord-25bc409831fa4bc291bc73bcdc659c5f
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08916593B2

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