Triethylamine → phenyl N-[4-(4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate

HRID 2066186Notes

Reaction equation

HRID 2066186 reaction equation
[C:1]1([O:7][C:8](=[O:33])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][C:42]([C:44]2([C:47](O)=[O:48])[CH2:46][CH2:45]2)=[O:43])=[CH:37][CH:36]=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:33])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:27]=[CH:28][C:29]([NH:32][C:47]([C:44]4([C:42](=[O:43])[NH:41][C:38]5[CH:37]=[CH:36][C:35]([F:34])=[CH:40][CH:39]=5)[CH2:45][CH2:46]4)=[O:48])=[CH:30][CH:31]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:11])[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 59596898[4-(4-Aminophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Product 1

HCID 59596935phenyl N-[4-(4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamateYield 70.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A crude product of [4-(4-aminophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (820 mg) was dissolved in N,N-dimethylformamide (15 ml). 1-(4-Fluorophenylcarbamoyl)cyclopropanecarboxylic acid (830 mg), triethylamine (0.519 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.65 g) were added in this order under a nitrogen atmosphere at room temperature, followed by stirring for 15.5 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 evaporated 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 to provide the titled compound as white foam (845.8 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 evaporated 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

Sources & evidence

ORD record
ord-1c7b84ad071c4d54bf42321cef960ef7
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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