(S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanone → (S)-2-chloro-5-fluoro-N-(3-methylenecyclohexyl)pyrimidin-4-amine

HRID 74977Notes

Reaction equation

HRID 74977 reaction equation
[CH3:1][Si](N([Li])[Si](C)(C)C)(C)C.[Cl:11][C:12]1[N:17]=[C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][C:21](=O)[CH2:20]2)[C:15]([F:26])=[CH:14][N:13]=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[Cl:11][C:12]1[N:17]=[C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][C:21](=[CH2:1])[CH2:20]2)[C:15]([F:26])=[CH:14][N:13]=1

Participants

5

Reactant 2

HCID 86667417(S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanone2×HCID 178418261HCID 178418261, compound

Product 1

HCID 86667428(S)-2-chloro-5-fluoro-N-(3-methylenecyclohexyl)pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of methyl(triphenyl)phosphonium bromide (0.86 g, 2.40 mmol) in THF (100 mL) in a flamed dry flask was added (bis(trimethylsilyl)amino)lithium (2.40 mL of 1 M solution, 2.40 mmol) at room temperature. The reaction mixture was allowed to stir at room temperature for 1 hr. A solution of (S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanone, 29b, (0.48 g, 2.00 mmol) in 20 mL of THF was added. The reaction was allowed to stir at room temperature for 2 hrs. The mixture was quenched by pouring into brine and the aqueous phase was extracted with EtOAc. The layers were separated and the organic was dried over MgSO4, filtered and evaporated to dryness. The crude residue was purified via silica gel chromatography (0-100% EtOAc/hexanes gradient) to afford 270 mg of the desired product: LCMS RT: 3.83 min, (M+1): 242.2.

Workup

  1. customdry flask
  2. stirringto stir at room temperature for 2 hrs
  3. customThe mixture was quenched
  4. additionby pouring into brine
  5. extractionthe aqueous phase was extracted with EtOAc
  6. customThe layers were separated
  7. dry with materialthe organic was dried over MgSO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe crude residue was purified via silica gel chromatography (0-100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-5f2f85aa76584a40a80c29f4b66159b4
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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