Potassium Carbonate → (R)-3-cyclopentyl-3-[4-(2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

HRID 449773Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 449773
Cl[C:2]1[C:3]2[CH:12]=[CH:11][NH:10][C:4]=2[N:5]=[C:6]([O:8][CH3:9])[N:7]=1.[CH:13]1([C@H:18]([N:22]2[CH:26]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:24]=[N:23]2)[CH2:19][C:20]#[N:21])[CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:13]1([C@H:18]([N:22]2[CH:26]=[C:25]([C:2]3[C:3]4[CH:12]=[CH:11][NH:10][C:4]=4[N:5]=[C:6]([O:8][CH3:9])[N:7]=3)[CH:24]=[N:23]2)[CH2:19][C:20]#[N:21])[CH2:17][CH2:16][CH2:15][CH2:14]1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 61402294-chloro-2-methoxy-7H-pyrrolo[2,3-d]pyrimidineHCID 58221004(betaR)-beta-Cyclopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrile

Produkt 1

HCID 58221013(R)-3-cyclopentyl-3-[4-(2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

4-Chloro-2-methoxy-7H-pyrrolo[2,3-d]pyrimidine (0.4 g, 2.18 mmol, Toronto Research Chemicals) and (R)-3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (0.824 g, 2.61 mmol, prepared as described in Org. Lett., 2009, 11(9), 1999-2002.) were dissolved in 1,4-dioxane (4 mL) and potassium carbonate (0.903 g, 6.54 mmol) in water (2 mL) was added. The mixture was degassed and tetrakis(triphenylphosphine)palladium(0) (0.126 g, 0.109 mmol) was added. The reaction mixture was heated to 100° C. for 16 h. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The combined extracts were dried over sodium sulfate, decanted and concentrated. Flash column chromatography, eluting with a gradient from 0-10% MeOH in methylene chloride was used to purify the product (670 mg, 91%). 1H NMR (300 MHz, CD3OD): δ 8.59 (s, 1H), 8.35 (s, 1H), 7.24 (d, 1H), 6.81 (d, 1H), 4.47 (dt, 1H), 4.04 (s, 3H), 3.21 (dd, 1H), 3.10 (dd, 1H), 2.62-2.44 (m, 1H), 2.02-1.86 (m, 1H), 1.81-1.20 (m, 7H); LCMS (M+H)+: 337.0.

Aufarbeitung

  1. customThe mixture was degassed
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate three times
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. washFlash column chromatography, eluting with a gradient from 0-10% MeOH in methylene chloride
  8. customto purify the product (670 mg, 91%)

Quellen und Nachweise

ORD-Eintrag
ord-2c2579b84feb44bca8d7fe18984881e3
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486902B2

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