Cesium fluoride → HCID 178462223、化合物

HRID 1406318ノート

反応式

HRID 1406318 の反応式
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]

参加物

7

反応物 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、化合物HCID 178514824HCID 178514824、化合物

生成物 1

HCID 178462223HCID 178462223、化合物

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 887Methanol溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-25bc409831fa4bc291bc73bcdc659c5f
出典データセット
uspto-grants-2014_12
特許番号
US08916593B2

反応ノート

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