Propylphosphonic acid → 2-(1-Cyclopropyl-5-trifluoromethyl-1H-pyrazol-4-yl)-N-[5-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-acetamide

HRID 82111

反応式

HRID 82111 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([CH:19]([CH3:21])[CH3:20])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[CH:22]1([N:25]2[C:29]([C:30]([F:33])([F:32])[F:31])=[C:28]([CH2:34][C:35](O)=[O:36])[CH:27]=[N:26]2)[CH2:24][CH2:23]1.CCCP(O)(O)=O>C1COCC1>[CH:22]1([N:25]2[C:29]([C:30]([F:32])([F:31])[F:33])=[C:28]([CH2:34][C:35]([NH:1][C:2]3[CH:7]=[N:6][CH:5]=[C:4]([C:8]([C:10]4[C:18]5[CH:17]=[N:16][CH:15]=[N:14][C:13]=5[N:12]([CH:19]([CH3:21])[CH3:20])[CH:11]=4)=[O:9])[CH:3]=3)=[O:36])[CH:27]=[N:26]2)[CH2:23][CH2:24]1

参加物

5

反応物 3

HCID 204484Propylphosphonic acidHCID 708172792-(1-Cyclopropyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)acetic acidHCID 70817456(5-aminopyridin-3-yl)(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanone

生成物 1

HCID 708173662-(1-Cyclopropyl-5-trifluoromethyl-1H-pyrazol-4-yl)-N-[5-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-3-yl]-acetamide収率 76%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (5-Amino-pyridin-3-yl)-(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanone (Preparation 95, 50 mg, 0.17 mmol), (1-Cyclopropyl-5-trifluoromethyl-1H-pyrazol-4-yl)-acetic acid (Preparation 141, 47.1 mg, 0.21 mmol) and TEA (0.08 mL, 0.62 mmol) in THF (1 mL), 1-propylphosphonic acid cyclic anhydride (50% solution in EtOAc, 0.26 mL, 0.44 mmol) was added and the mixture was stirred at room temperature for 14 hours. The reaction mixture was evaporated under reduced pressure and the residue partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and dried (Na2SO4) and evaporated in vacuo. Purification by column chromatography on silica gel (gradient of EtOAc:Hexane 0:100 to 80:20) gave the title compound as a white solid in 76% yield, 67 mg. 1H NMR (400 MHz, DMSO-D6) δ: 1.05-1.07 (m, 2H), 1.08-1.15 (m, 2H), 1.54 (d, 6H), 3.73-3.76 (m, 3H), 5.06-5.13 (m, 1H), 7.55 (s, 1H), 8.44 (s, 1H), 8.51 (s, 1H), 8.73 (s, 1H), 8.94 (d, 1H), 8.99 (s, 1H), 9.44 (s, 1H), 10.61 (s, 1H). LCMS (System 10): Rt=3.03 min m/z 498 [M+H]+

後処理

  1. customThe reaction mixture was evaporated under reduced pressure
  2. customthe residue partitioned between water and ethyl acetate
  3. washThe organic layer was washed with saturated sodium bicarbonate solution
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customPurification by column chromatography on silica gel (gradient of EtOAc:Hexane 0:100 to 80:20)

出典と根拠

ORDレコード
ord-3d37de3ca2ef415497310b44559ae9ca
出典データセット
uspto-grants-2014_09
特許番号
US08846698B2

関連ノート

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