Triethylamine → phenyl N-[4-(3-fluoro-4-{[1-(phenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate

HRID 2265616Notes

Reaction equation

HRID 2265616 reaction equation
[C:1]1([O:7][C:8](=[O:34])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH2:32])=[C:28]([F:33])[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.[C:35]1([NH:41][C:42]([C:44]2([C:47](O)=[O:48])[CH2:46][CH2:45]2)=[O:43])[CH:40]=[CH:39][CH:38]=[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:34])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:47]([C:44]4([C:42](=[O:43])[NH:41][C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH2:45][CH2:46]4)=[O:48])=[C:28]([F:33])[CH:27]=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:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 190968711-(Phenylcarbamoyl)cyclopropanecarboxylic acidHCID 67136032[4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Product 1

HCID 59596979phenyl N-[4-(3-fluoro-4-{[1-(phenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamateYield 87.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A crude product of [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (219 mg) was dissolved in N,N-dimethylformamide (5 ml). 1-(Phenylcarbamoyl)cyclopropanecarboxylic acid (196 mg), triethylamine (0.133 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (422 mg) were added under a nitrogen atmosphere at room temperature, followed by stirring overnight. Liquid-liquid separation was carried out after addition of ethyl acetate and water to the reaction mixture. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was removed and the resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:2) to provide the titled compound as white powder (271 mg).

Workup

  1. customLiquid-liquid separation
  2. additionafter addition of ethyl acetate and water to the reaction mixture
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed
  6. customthe resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=3:2)

Sources & evidence

ORD record
ord-610333e522e74125a987e76cfc84a07b
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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