Water → 4-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile

HRID 2367280Notes

Reaction equation

HRID 2367280 reaction equation
C(=O)([O-])[O-].[K+].[K+].O.Cl[C:9]1[CH:14]=[C:13]([N:15]2[CH2:19][CH2:18][CH2:17][CH:16]2[C:20]([F:23])([F:22])[F:21])[N:12]=[C:11]([NH2:24])[N:10]=1.[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[F:36])#[N:26]>O1CCOCC1.CCOC(C)=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>[NH2:24][C:11]1[N:10]=[C:9]([C:30]2[CH:31]=[CH:32][C:27]([C:25]#[N:26])=[C:28]([F:36])[CH:29]=2)[CH:14]=[C:13]([N:15]2[CH2:19][CH2:18][CH2:17][CH:16]2[C:20]([F:23])([F:22])[F:21])[N:12]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 585047924-Chloro-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-2-pyrimidinamine

Product 1

HCID 585045294-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrileYield 59.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Potassium carbonate (129 mg, 0.934 mmol) and water (1.5 mL) were added to a stirring mixture of 4-chloro-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-2-pyrimidinamine (83 mg, 0.311 mmol) and (4-cyano-3-fluorophenyl)boronic acid (61.6 mg, 0.374 mmol) in 1,4-dioxane (3 mL). After degassing, Pd(PPh3)4 (29 mg, 0.025 mmol) was added, and the vessel was seal and heated at 100° C. in an oil bath overnight. LCMS showed complete conversion. The mixture was diluted with EtOAc, and washed with water. The aqueous layer was back-extracted with EtOAc. The combined organics were washed with brine, dried (Na2SO4) filtered and evaporated. Purification by silica gel chromatography (Analogix RS-4 g) eluting with 5-20% EtOAc—CHCl3 afforded the title compound (65 mg) as a white foam. The sample contained some PH3P/Ph3PO by NMR, but was suitable for subsequent reactions. LC-MS (ES) m/z=352 [M+H]+.

Workup

  1. customAfter degassing
  2. customthe vessel was seal
  3. washwashed with water
  4. extractionThe aqueous layer was back-extracted with EtOAc
  5. washThe combined organics were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by silica gel chromatography (Analogix RS-4 g)
  10. washeluting with 5-20% EtOAc—CHCl3

Sources & evidence

ORD record
ord-0701417367b949039d4b1cc788dce9fa
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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