Trifluoroacetic acid → HCID 18008930, compound

HRID 987531Notes

Reaction equation

HRID 987531 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH:25]([CH3:32])[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:23]=2)[N:18]([C:33](=[O:54])[CH2:34][C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:42]([NH:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[CH3:51])=[O:43])=[C:37]([O:52][CH3:53])[CH:36]=2)[CH2:17][CH2:16]1)=O)(C)(C)C.[OH-].[Na+]>ClCCl>[CH2:30]([O:29][C:27](=[O:28])[CH2:26][CH:25]([C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[N:18]([C:33](=[O:54])[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][C:42]([NH:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[CH3:51])=[O:43])=[C:37]([O:52][CH3:53])[CH:36]=1)[CH2:17][CH2:16][NH:15]2)[CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 53984519HCID 53984519, compound

Product 1

HCID 18008930HCID 18008930, compoundYield 87.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (574 μl) was added to a stirred solution of 7-(2-ethoxycarbonyl-1-methyl-ethyl)-4-{[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetyl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester (376 mg, Reference Example 18) in dichloromethane (4 ml) at 0° C. After stirring at 0° C. for 2 hours a further aliquot of trifluoroacetic acid (3.5 ml) was added and stirring was continued at 0° C. for a further 4 hours. The reaction mixture was poured onto a mixture of ice (75 ml) and sodium hydroxide solution (55 ml, 1M). The resulting mixture was extracted three times with dichloromethane (50 ml). The combined extracts were washed twice with water (20 ml), then dried over magnesium sulfate and then evaporated (40 mbar, 40° C.). The residue was subjected to flash chromatography (20 g silica, 0.040-0.063 mm particle size) eluting with a mixture of dichloromethane and methanol (99:1, v/v) to give the title compound as a white powder (279 mg). TLC: RF=43/64 (dichloromethane:methanol, 9:1). 1H NMR (250 MHz, (CD3)2SO, at a temperature of 373° K.]: δ1.16 (t, J=7 Hz, 3H); 1.23 (d, J=7.5 Hz, 3H); 2.28 (s, 3H); from 2.45 to 2.55 (m, 2H); 3.06 (m, 1H); 3.25 (m, 2H); 3.69 (m, 2H); 3.82 (s, 2H); 3.85 (s, 3H); 4.05 (q, J=7 Hz, 2H); 5.73 (broad band :1H); 6.43 (dd, J=8 and 2 Hz, 1H); 6.50 (d, J=2 Hz, 1H); 6.70 (dd, J=9 and 1.5 Hz, 1H); 6.81 (d, J=1.5 Hz, 1H); 6.97 (broad t, J=7.5 Hz, 1H); from 7.10 to 7.30 (m, 3H); 7.71 (broad d, J=9 Hz, 1H); 7.98 (d, J=8.5 Hz, 1H); 8.25 (broad s, 1H); 8.29 (broad s, 1H). MS (EI): 544(M+).

Workup

  1. additionwas added
  2. extractionThe resulting mixture was extracted three times with dichloromethane (50 ml)
  3. washThe combined extracts were washed twice with water (20 ml)
  4. dry with materialdried over magnesium sulfate
  5. customevaporated (40 mbar, 40° C.)
  6. washeluting with a mixture of dichloromethane and methanol (99:1

Sources & evidence

ORD record
ord-65074860b64949c4a28977d6876df4ab
Source dataset
uspto-grants-2003_10
Patent number
US06632814B1

Reaction notes

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