Acetamide → 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(4-(4'-methyl-[1,1'-biphenyl]-4-yl)oxazol-2-yl)benzyl)benzamido)acetic acid

HRID 923575Notes

Reaction equation

C([NH2:4])(=O)C.B(F)(F)F.CCOCC.C([O:18][C:19](=[O:72])[CH2:20][N:21]([CH2:46][C:47]1[CH:71]=[CH:70][C:50]([C:51]([O:53][CH2:54][C:55]([C:57]2[CH:62]=[CH:61][C:60]([C:63]3[CH:68]=[CH:67][C:66]([CH3:69])=[CH:65][CH:64]=3)=[CH:59][CH:58]=2)=O)=O)=[CH:49][CH:48]=1)[C:22](=[O:45])[C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:44])[CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=2[C:40]([F:43])([F:42])[F:41])=[CH:25][CH:24]=1)(C)(C)C.N#N>C(Cl)Cl.C(#N)C>[CH3:39][O:38][C:35]1[CH:36]=[CH:37][C:32]([CH2:31][C:30]([NH:29][C:26]2[CH:27]=[CH:28][C:23]([C:22]([N:21]([CH2:20][C:19]([OH:18])=[O:72])[CH2:46][C:47]3[CH:48]=[CH:49][C:50]([C:51]4[O:53][CH:54]=[C:55]([C:57]5[CH:58]=[CH:59][C:60]([C:63]6[CH:64]=[CH:65][C:66]([CH3:69])=[CH:67][CH:68]=6)=[CH:61][CH:62]=5)[N:4]=4)=[CH:70][CH:71]=3)=[O:45])=[CH:24][CH:25]=2)=[O:44])=[C:33]([C:40]([F:42])([F:43])[F:41])[CH:34]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To stirring acetamide (292 mg, 4.95 mmol) at 100° C. was added boron trifluoride etherate (16.0 μl, 0.130 mmol). The temperature was raised to 140° C. and a solution of 2-(4′-methyl-[1,1′-biphenyl]-4-yl)-2-oxoethyl 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)benzoate INT-38 (100 mg, 0.124 mmol) in DCM (1 mL) was added drop wise under a stream of N2. After 1 h, the reaction mixture was allowed to cool to room temperature and acetonitrile (2 mL) was added. The reaction mixture was stirred at room temperature for 2 h and the precipitate was collected by filtration and washed with acetonitrile (0.5 mL) and isohexanes (2 mL). The isolated precipitate was further re-slurried from DCM (2 mL) to afford 39 mg (43%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(4-(4′-methyl-[1,1′-biphenyl]-4-yl)oxazol-2-yl)benzyl)benzamido)acetic acid 360 as a white solid. LCMS-ESI (m/z) calculated for C42H34F3N3O6: 733; found 734 [M+H]+, tR=9.18 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.84 (s, 1H), 10.34 (s, 1H), 8.78 (s, 1H), 8.10-8.03 (m, 2H), 7.98-7.92 (m, 2H), 7.80-7.73 (m, 2H), 7.68-7.53 (m, 5H), 7.50-7.35 (m, 4H), 7.33-7.27 (d, J=7.8 Hz, 2H), 7.26-7.16 (m, 2H), 4.75 (s, 1H), 4.67 (s, 1H), 4.03 (m, 1H), 3.95 (s, 1H), 3.89-3.79 (m, 5H), 2.37 (s, 3H).

Workup

temperatureto cool to room temperature
filtrationthe precipitate was collected by filtration
washwashed with acetonitrile (0.5 mL) and isohexanes (2 mL)

Sources & evidence

ORD record: ord-3140ece938ea4e2a95e5151c7c18b553
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278910B2

Reaction notes

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