Water → 3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-N-(2-methylamino-ethoxy)-benzamide

HRID 2218480Notes

Reaction equation

HRID 2218480 reaction equation
FC(F)(F)C(O)=O.C(O[C:13](=O)[N:14]([CH2:16][CH2:17][O:18][NH:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[C:24]([F:29])[C:23]=1[NH:30][C:31]1[CH:36]=[CH:35][C:34]([I:37])=[CH:33][C:32]=1[CH3:38])=[O:21])C)(C)(C)C.O.C(=O)(O)[O-].[Na+]>ClCCl.CCOCC>[F:29][C:24]1[C:23]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([I:37])=[CH:33][C:32]=2[CH3:38])=[C:22]([CH:27]=[CH:26][C:25]=1[F:28])[C:20]([NH:19][O:18][CH2:17][CH2:16][NH:14][CH3:13])=[O:21]

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86591460[2-({1-[3,4-Difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-methanoyl}-aminooxy)-ethyl]-methyl-carbamic acid tert-butyl ester

Product 1

HCID 101155383,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-N-(2-methylamino-ethoxy)-benzamideYield 45.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (3.0 mL, 39 mmol) was added to a 0° C. solution of [2-({1-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-methanoyl}-aminooxy)-ethyl]-methyl-carbamic acid tert-butyl ester (0.75 g, 1.3 mmol) in dichlormethane (12 mL). The resultant solution was stirred 2.5 h at 0° C. and diluted with ether (50 mL). Water (20 mL) was added and, with vigorous stirring, the pH of the aqueous layer was adjusted to pH 8 with saturated aqueous sodium bicarbonate. The heterogeneous mixture was stirred 30 min and the precipitate was removed by filtration and washed with water-ethanol (2:1) and acetone. The solid (471 mg) was dried overnight in vacuo and was further triturated with hot methanol and dried at 70° C. under reduced pressure to afford 3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-N-(2-methylamino-ethoxy)-benzamide (272 mg) as a white powder: m.p. 183-185 (dec); 1 H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1 H), 7.69 (t, J=7.0 Hz, 1 H), 7.46 (d, J=1.7 Hz, 1 H), 7.33 (dd, J=8.6, 2.0 Hz, 1 H), 6.95 (app q, J=9.0 Hz, 1 H), 6.40 (t, J=7.8 Hz, 1 H), 3.87 (br t, J=4.4 Hz, 2 H), 2.82 (br s, 2 H), 2.47 (s, 3 H), 2.24 (s, 3 H); 19F NMR (376 MHz, DMSO-d6) δ −137.7 (d, J=7.6 Hz), −143.3 (d, J=20.2 Hz). Anal Calcd./Found for C17H18F2IN3O2+0.07 C4H10O: C, 44.50/44.61; H, 4.01/3.97; N, 9.01/8.72.

Workup

  1. customthe precipitate was removed by filtration
  2. washwashed with water-ethanol (2:1) and acetone
  3. dry with materialThe solid (471 mg) was dried overnight in vacuo
  4. customwas further triturated with hot methanol
  5. customdried at 70° C. under reduced pressure

Sources & evidence

ORD record
ord-86446350bd3e488aa47c4724c1f1e4e0
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

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