Cesium carbonate → 2-Chloro-9-(2-methoxy-ethyl)-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2234407

反応式

HRID 2234407 の反応式
Br[C:2]1[C:3]([N:9]([CH2:16][CH2:17][O:18][CH3:19])[CH2:10][CH2:11][C:12]([NH:14][CH3:15])=[O:13])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:5]1[N:4]=[C:3]2[C:2]([N:14]([CH3:15])[C:12](=[O:13])[CH2:11][CH2:10][N:9]2[CH2:16][CH2:17][O:18][CH3:19])=[CH:7][N:6]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2 回HCID 866175793-[(5-bromo-2-chloro-pyrimidin-4-yl)-(2-methoxyethyl)amino]-N-methyl-propanamide2 回

生成物 1

HCID 866175782-Chloro-9-(2-methoxy-ethyl)-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one収率 18.2%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

3-[(5-bromo-2-chloro-pyrimidin-4-yl)-(2-methoxyethyl)amino]-N-methyl-propanamide (Intermediate 110; 1.12 g, 3.185 mmol) was suspended in dioxane (70 mL), Caesium Carbonate (2.08 g, 6.37 mmol) added and the mixture bubbled with nitrogen for 10 minutes. Tris(dibenzylideneacetone)dipalladium(0) (175 mg, 0.151 mmol) and XANTPHOS (166 mg, 0.287 mmol) were added and the mixture heated to 100° C. for 20 hrs. A further 0.06 equivalent of Tris(dibenzylideneacetone)dipalladium(0) and 0.09 equivalent of XANTPHOS were added and heating continued for a further 2 hrs. The reaction mixture was cooled to room temperature filtered and the filter cake washed with DCM. The filtrate was evaporated and dissolved in DCM and purified on silica eluting with a gradient of 40-55% Ethyl Acetate/iso-hexane then 55% Ethyl Acetate/iso-hexane and finally 70% Ethyl Acetate/iso-hexane. Fractions containing product were combined and evaporated to a yellow solid. Which was purified by base modified reverse phase HPLC to yield the title compound as a white solid (157 mg, 18%)

後処理

  1. customthe mixture bubbled with nitrogen for 10 minutes
  2. temperatureheating
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. washthe filter cake washed with DCM
  6. customThe filtrate was evaporated
  7. dissolutiondissolved in DCM
  8. custompurified on silica eluting with a gradient of 40-55% Ethyl Acetate/iso-hexane
  9. additionFractions containing product
  10. customevaporated to a yellow solid
  11. customWhich was purified by base modified reverse phase HPLC

出典と根拠

ORDレコード
ord-c09119b498a549f9aea3c5dc8ed49eb3
出典データセット
uspto-grants-2010_05
特許番号
US07709471B2

関連ノート

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