Triethylamine → [4-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

HRID 2265605Notes

Reaction equation

HRID 2265605 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])=[CH:28][C:27]=3[F:33])[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:35][C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]([C:45]2([C:48](O)=[O:49])[CH2:47][CH2:46]2)=[O:44])=[CH:38][CH:37]=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:48]([C:45]4([C:43](=[O:44])[NH:42][C:39]5[CH:38]=[CH:37][C:36]([F:35])=[CH:41][CH:40]=5)[CH2:46][CH2:47]4)=[O:49])=[CH:28][C:27]=3[F:33])[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 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 59596934[4-(4-Amino-2-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Product 1

HCID 59597000[4-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl esterYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A crude product of [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (1.617 g) was dissolved in N,N-dimethylformamide (25 ml). 1-(4-Fluorophenylcarbamoyl)cyclopropanecarboxylic acid (1.26 g), triethylamine (0.786 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (2.49 g) were added thereto 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 to give residue, which was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:1) to provide the titled compound as white powder (1.007 g).

Workup

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

Sources & evidence

ORD record
ord-215cbb83b4f748efb2e19a168536e252
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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