Sodium hydride → ethyl 1-amino-4-(4-amino-3-fluorophenyl)-5-cyano-1H-pyrrole-3-carboxylate

HRID 2197523Notes

Reaction equation

HRID 2197523 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][NH:13][C:14]=2[C:15]#[N:16])=[CH:6][C:5]=1[F:22].[NH2:23]OP(=O)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[NH2:23][N:13]1[C:14]([C:15]#[N:16])=[C:10]([C:7]2[CH:8]=[CH:9][C:4]([NH2:3])=[C:5]([F:22])[CH:6]=2)[C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10955453O-(Diphenylphosphinyl)hydroxylamineHCID 66786676HCID 66786676, compound

Product 1

HCID 66786981ethyl 1-amino-4-(4-amino-3-fluorophenyl)-5-cyano-1H-pyrrole-3-carboxylateYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Sodium hydride (60% dispersion in oil, 1.7 g, 43 mmol) was added in portions to a solution of ethyl 4-(4-amino-3-fluorophenyl)-5-cyano-1H-pyrrole-3-carboxylate (9.0 g, 33 mmol) in DMF (290 mL). The suspension was stirred for 30 min and then (aminooxy)(diphenyl)phosphine oxide (9.9 g, 43 mmol) was added. The reaction was warmed (60° C.) for 4 h and then cooled to rt. The reaction was quenched by slow addition of water (10 mL) and the solvents were evaporated under reduced pressure. The residue was dissolved in ethyl acetate (500 mL) and the solution was washed with saturated aqueous sodium bicarbonate solution (2×250 mL) and brine (250 mL). The organic layer was dried over sodium sulfate and evaporated. The residue was triturated with diethyl ether to give the desired product (7.8 g, 82%); 1H NMR (300 MHz, DMSO-d6) δ 7.57 (s, 1H), 7.05 (dd, J=12.7, 2.0 Hz, 1H), 6.91-6.95 (m, 1H), 6.75 (dd, J=9.5, 8.4 Hz, 1H), 6.57 (s, 2H), 5.36 (s, 2H), 4.09 (q, J=7.0 Hz, 2H), 1.16 (t, J=7.0 Hz, 3H); ES-MS m/z 289.0 (MH)+; HPLC RT (Method B) 2.61 min.

Workup

  1. temperaturecooled to rt
  2. customThe reaction was quenched by slow addition of water (10 mL)
  3. customthe solvents were evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (500 mL)
  5. washthe solution was washed with saturated aqueous sodium bicarbonate solution (2×250 mL) and brine (250 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customevaporated
  8. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-965f8c52dcea4ba29034f0642f7dfb60
Source dataset
uspto-grants-2012_12
Patent number
US08338594B2

Reaction notes

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