Triethylamine → HCID 59596966, compound

HRID 2066188Notes

Reaction equation

HRID 2066188 reaction equation
[C:1]1([O:7][C:8](=[O:25])[NH:9][C:10]2[CH:15]=[C:14]([O:16][C:17]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][C:18]=3[F:24])[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]2([C:39](O)=[O:40])[CH2:38][CH2:37]2)=[O:35])=[CH:29][CH:28]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[C:1]1([O:7][C:8](=[O:25])[NH:9][C:10]2[CH:15]=[C:14]([O:16][C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:39]([C:36]4([C:34](=[O:35])[NH:33][C:30]5[CH:29]=[CH:28][C:27]([F:26])=[CH:32][CH:31]=5)[CH2:37][CH2:38]4)=[O:40])=[CH:19][C:18]=3[F:24])[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 59596928[6-(4-Amino-2-fluorophenoxy)pyrimidin-4-yl]carbamic acid phenyl ester

Product 1

HCID 59596966HCID 59596966, compoundYield 20.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A crude product of [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]carbamic acid phenyl ester (303 mg) was dissolved in N,N-dimethylformamide (5 ml). 1-(4-Fluorophenylcarbamoyl)cyclopropanecarboxylic acid (497 mg), triethylamine (0.310 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (984 mg) were added in this order under a nitrogen atmosphere at room temperature, followed by stirring for 5 hr. Liquid-liquid separation was carried out after addition of ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate to the reaction mixture. The resultant organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give residue, which was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:3 to 1:1). Fractions containing the target compound were concentrated under reduced pressure, the resultant residue was purified again by silica gel column chromatography (eluent; heptane:ethyl acetate=2:3 to 1:1). Fractions containing the target compound were concentrated under reduced pressure to provide the titled compound as white powder (100.4 mg).

Workup

  1. customLiquid-liquid separation
  2. additionafter addition of ethyl acetate
  3. washThe resultant organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customto give residue, which
  7. customwas purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:3 to 1:1)
  8. additionFractions containing the target compound
  9. concentrationwere concentrated under reduced pressure
  10. customthe resultant residue was purified again by silica gel column chromatography (eluent; heptane:ethyl acetate=2:3 to 1:1)
  11. additionFractions containing the target compound
  12. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-8d5cf9deb36648da8d87c2b0cec84712
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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