Diisopropylethylamine → tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate

HRID 923583Notes

Reaction equation

HRID 923583 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH:10]=[C:11]([C:13]3[CH:28]=[CH:27][C:16]([CH2:17][NH:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:15][CH:14]=3)[N:12]=2)=[CH:4][CH:3]=1.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38]([NH:40][C:41]2[CH:49]=[CH:48][C:44]([C:45](O)=[O:46])=[CH:43][CH:42]=2)=[O:39])=[C:33]([C:50]([F:53])([F:52])[F:51])[CH:32]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][CH:10]=[C:11]([C:13]3[CH:28]=[CH:27][C:16]([CH2:17][N:18]([CH2:19][C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[C:45](=[O:46])[C:44]4[CH:48]=[CH:49][C:41]([NH:40][C:38](=[O:39])[CH2:37][C:34]5[CH:35]=[CH:36][C:31]([O:30][CH3:29])=[CH:32][C:33]=5[C:50]([F:53])([F:51])[F:52])=[CH:42][CH:43]=4)=[CH:15][CH:14]=3)[N:12]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71076724Tert-butyl 2-((4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)amino)acetateHCID 710767434-(2-(4-Methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid

Product 1

HCID 71076598tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetateYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of tert-butyl 2-((4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)amino)acetate INT-44 (220 mg, 0.496 mmol), 4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid (175 mg, 0.496 mmol) and DIEA (137 μl, 0.744 mmol) in DMF (4 mL) was added HATU (198 mg, 0.521 mmol). The reaction mixture was stirred at room temperature for 16 h then diluted with DCM (4 mL), stirred with NaHCO3 (15 mL) for 15 min, split through a hydrophobic frit and evaporated. The crude product was purified by column chromatography (acetonitrile/DCM) to gave 262 mg (68%) of tert-butyl 2-(N-(4-(2-(4-bromophenyl)oxazol-4-yl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-45 as an off-white solid. LCMS-ESI (m/z) calculated for C39H35BrF3N3O6: 777; found 778 [M+H]+, tR=3.20 min (Method 5).

Workup

  1. customsplit through a hydrophobic frit
  2. customevaporated
  3. customThe crude product was purified by column chromatography (acetonitrile/DCM)

Sources & evidence

ORD record
ord-32c8e73ddc104d4689d93664c02ae8f5
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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