Cesium carbonate → HCID 46215101、化合物

HRID 62508ノート

反応式

HRID 62508 の反応式
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[C:24]([CH2:30][OH:31])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:21][C:22]2[N:26]([CH:27]([CH3:28])[CH3:29])[N:25]=[C:24]([CH2:30][OH:31])[CH:23]=2)=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamideHCID 57516902[5-Amino-1-(propan-2-yl)-1H-pyrazol-3-yl]methanol

生成物 1

HCID 46215101HCID 46215101、化合物

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (188 mg, 0.602 mmol), [5-amino-1-(1-methylethyl)-1H-pyrazol-3-yl]methanol (140 mg, 0.90 mmol), cesium carbonate (589 mg, 1.81 mmol) and DMF (5 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (6.8 mg, 0.03 mmol) and BINAP (37.5 mg, 0.06 mmol) were added. The reaction mixture was heated in an oil bath at 90° C. for 5 hrs and then in a microwave at 150° C. for 40 min. It was evaporated and the residue was dissolved in MeOH, filtered thru celite and thru an Acrodisc and purified further using preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. EtOAc was added to the brown oil residue. Then the mixture was heated and hexane was added dropwise. A light yellow precipitate crashed out upon sonication. It was filtered off and dried under vacuum at 40° C. for 12 hrs. LC-MS [M+H]+=431.2. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (br. s., 1 H) 9.54 (br. s., 1 H) 8.54 (s, 1 H) 7.96-8.01 (m, 1 H) 7.52-7.62 (m, 3 H) 7.11-7.16 (m, 1 H) 6.70 (s, 1 H) 6.10 (s, 1 H) 4.95 (t, J=5.81 Hz, 1 H) 4.43 (dt, J=13.14, 6.57 Hz, 1 H) 4.33 (d, J=5.56 Hz, 2 H) 3.71 (s, 3 H) 1.29 (d, J=6.57 Hz, 6 H).

後処理

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customIt was evaporated
  3. dissolutionthe residue was dissolved in MeOH
  4. filtrationfiltered
  5. custompurified further
  6. customevaporated
  7. additionEtOAc was added to the brown oil residue
  8. temperatureThen the mixture was heated
  9. additionhexane was added dropwise
  10. customA light yellow precipitate crashed out upon sonication
  11. filtrationIt was filtered off
  12. customdried under vacuum at 40° C. for 12 hrs

出典と根拠

ORDレコード
ord-f16b19b74291420a965034a3c3df8ecb
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

反応ノート

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