Potassium Phosphate, Tribasic → methyl 4-(tert-butoxycarbonylamino)-1-(5-cyclopropyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylate

HRID 423080

Reaktionsgleichung

Reaktionsgleichung von HRID 423080
Br[C:2]1[C:10]2[C:9]([N:11]3[CH2:16][CH2:15][C:14]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])([C:17]([O:19][CH3:20])=[O:18])[CH2:13][CH2:12]3)=[N:8][CH:7]=[N:6][C:5]=2[N:4]([S:29]([C:32]2[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=2)(=[O:31])=[O:30])[CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P([CH:60]2[CH2:65][CH2:64]CCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1>C1(C)C=CC=CC=1.O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:25]([O:24][C:22]([NH:21][C:14]1([C:17]([O:19][CH3:20])=[O:18])[CH2:15][CH2:16][N:11]([C:9]2[C:10]3[C:2]([CH:64]4[CH2:65][CH2:60]4)=[CH:3][N:4]([S:29]([C:32]4[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[C:5]=3[N:6]=[CH:7][N:8]=2)[CH2:12][CH2:13]1)=[O:23])([CH3:28])([CH3:27])[CH3:26]

Komponenten

9

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 57750316methyl 1-(5-bromo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-(tert-butoxycarbonylamino)piperidine-4-carboxylate2×

Produkt 1

HCID 57750287methyl 4-(tert-butoxycarbonylamino)-1-(5-cyclopropyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylateAusbeute 218 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

Methyl 1-(5-bromo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-(tert-butoxycarbonylamino)piperidine-4-carboxylate (Intermediate 62) (1.1 g, 1.81 mmol), potassium phosphate tribasic (1.343 g, 6.33 mmol), tricyclohexyl phosphine (0.101 g, 0.36 mmol) and cyclopropylboronic acid (0.438 g, 4.34 mmol) were taken up in toluene (10 mL) and water (0.400 mL). The mixture was purged with nitrogen for 30 minutes then palladium(II) acetate (0.041 g, 0.18 mmol) was added. The mixture was heated to 75° C. for 6 hours and then allowed to cool and stir at room temperature overnight. The reaction mixture was diluted with EtOAc (75 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 10 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 4-(tert-butoxycarbonylamino)-1-(5-cyclopropyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylate (0.447 g, 43.4%) as a cream solid.

Aufarbeitung

  1. customThe mixture was purged with nitrogen for 30 minutes
  2. temperatureto cool
  3. washwashed sequentially with water (50 mL) and saturated brine (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 10 to 30% EtOAc in isohexane
  9. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-4e664570ee874106aafb0bfd960da726
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101623B2

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