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

HRID 449773Notes

Reaction equation

HRID 449773 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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%)

Sources & evidence

ORD record
ord-2c2579b84feb44bca8d7fe18984881e3
Source dataset
uspto-grants-2013_07
Patent number
US08486902B2

Reaction notes

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