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

Reaktionsgleichung

Reaktionsgleichung von HRID 82111
[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

Komponenten

5

Edukt 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

Produkt 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]-acetamideAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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]+

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-3d37de3ca2ef415497310b44559ae9ca
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846698B2

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