Cesium carbonate → N-(2-(2-Chloro-6-fluorophenyl)thiazolo[5,4-c]pyridin-4-yl)cyclopropanecarboxamide

HRID 2366198ノート

反応式

HRID 2366198 の反応式
Cl[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH:19]1([C:22]([NH2:24])=[O:23])[CH2:21][CH2:20]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.C(=O)([O-])[O-].[Cs+].[Cs+]>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:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:24][C:22]([CH:19]3[CH2:21][CH2:20]3)=[O:23])=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 80376Cyclopropanecarboxamide2 回HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2 回HCID 867233054-Chloro-2-(2-chloro-6-fluorophenyl)-thiazolo[5,4-c]pyridine

生成物 1

HCID 56953389N-(2-(2-Chloro-6-fluorophenyl)thiazolo[5,4-c]pyridin-4-yl)cyclopropanecarboxamide収率 30.4%

試薬・触媒・溶媒 2

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

実験手順

A mixture of 4-chloro-2-(2-chloro-6-fluoro-phenyl)-thiazolo[5,4-c]pyridine (0.050 g, 0.17 mmol), cyclopropanecarboxamide (0.016 g, 0.18 mmol), Pd2(dba)3 (0.008 g, 0.009 mmol), XantPhos (0.010 g, 0.017 mmol) and cesium carbonate (0.139 g, 0.43 mmol) in dioxane (1.7 mL) was degassed with nitrogen then subjected to microwave irradiation at 170° C. for 60 minutes. Further cyclopropanecarboxamide (0.006 g, 0.08 mmol), Pd2(dba)3 (0.010 g, 0.010 mmol) and XantPhos (0.012 g, 0.021 mmol) were added. The mixture was degassed with nitrogen then subjected to microwave irradiation at 200° C. for 90 minutes. Water and DCM were added and the resulting mixture was filtered through Celite®. The layers of the filtrate were separated via a phase separator and the organic phase concentrated under reduced pressure. The residue was loaded onto an Isolute® SCX-2 cartridge that was washed with MeOH and the product eluted with 2M ammonia in MeOH. The relevant fractions were combined, concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography (0-30% EtOAc in DCM) to give the desired compound as an off-white solid (0.018 g, 30% yield). 1H NMR (300 MHz, DMSO-d6): δ 11.40 (s, 1H), 8.45 (d, J=5.6 Hz, 1H), 7.92 (d, J=5.6 Hz, 1H), 7.69 (dd, J=8.3, 6.1 Hz, 1H), 7.59-7.58 (m, 1H), 7.52-7.49 (m, 1H), 2.13-2.03 (s, 1H), 0.91-0.90 (m, 4H). LCMS (Method D): RT=3.36 min, m/z: 348 [M+H+].

後処理

  1. customwas degassed with nitrogen
  2. customirradiation at 170° C. for 60 minutes
  3. customThe mixture was degassed with nitrogen
  4. customirradiation at 200° C. for 90 minutes
  5. additionWater and DCM were added
  6. filtrationthe resulting mixture was filtered through Celite®
  7. customThe layers of the filtrate were separated via a phase separator
  8. concentrationthe organic phase concentrated under reduced pressure
  9. washwas washed with MeOH
  10. washthe product eluted with 2M ammonia in MeOH
  11. concentrationconcentrated under reduced pressure
  12. customthe resultant residue was purified by silica gel flash chromatography (0-30% EtOAc in DCM)

出典と根拠

ORDレコード
ord-ba3cfe03474646ebb2266b806d39b0e2
出典データセット
uspto-grants-2014_04
特許番号
US08697708B2

反応ノート

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