Potassium Carbonate → 4-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(5-methyl-2-oxo-3-{5-[2-(trifluoro-methoxy)phenyl]pyridin-2-yl}-1,3-oxazolidin-5-yl)methyl]benzamide

HRID 2066820Notes

Reaction equation

HRID 2066820 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][C:11]([CH2:14][NH:15][C:16](=[O:37])[C:17]3[CH:22]=[CH:21][C:20]([C:23]4[O:24][C:25]5[C:31]([CH:32]([CH3:34])[CH3:33])=[CH:30][C:29]([C:35]#[N:36])=[CH:28][C:26]=5[N:27]=4)=[CH:19][CH:18]=3)([CH3:13])[O:10][C:9]2=[O:38])=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:45][C:46]([F:58])([F:57])[O:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1B(O)O>O1CCCC1.O.C(P([C-]1C=CC=C1)C(C)(C)C)(C)(C)C.[CH-]1C=CC=C1.[Fe+2].[Pd]>[C:35]([C:29]1[CH:30]=[C:31]([CH:32]([CH3:34])[CH3:33])[C:25]2[O:24][C:23]([C:20]3[CH:21]=[CH:22][C:17]([C:16]([NH:15][CH2:14][C:11]4([CH3:13])[O:10][C:9](=[O:38])[N:8]([C:5]5[CH:4]=[CH:3][C:2]([C:49]6[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=6[O:47][C:46]([F:45])([F:58])[F:57])=[CH:7][N:6]=5)[CH2:12]4)=[O:37])=[CH:18][CH:19]=3)=[N:27][C:26]=2[CH:28]=1)#[N:36]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 25151852N-{[3-(5-chloropyridin-2-yl)-5-methyl-2-oxo-1,3-oxazolidin-5-yl]methyl}-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide

Product 1

HCID 684107154-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(5-methyl-2-oxo-3-{5-[2-(trifluoro-methoxy)phenyl]pyridin-2-yl}-1,3-oxazolidin-5-yl)methyl]benzamideYield 25.1%

Reagents, catalysts & solvents 3

HCID 178454864HCID 178454864, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of N-{[3-(5-chloropyridin-2-yl)-5-methyl-2-oxo-1,3-oxazolidin-5-yl]methyl}-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide (26 mg, EXAMPLE 50) and potassium carbonate (35 mg) in 0.5 ml of tetrahydrofuran and 0.5 ml of water was added 2-trifluoromethoxyphenylboronic acid (10 mg) and palladium di-tert-butylphosphinoferrocene (7 mg). The mixture was heated via microwave for 10 min at 100° C. The sample was cooled to room temperature, and was purified via column chromatography on a Biotage Horizon 40M column eluting with 0% ethyl acetate in hexanes (1 column volume), followed by a gradient to 100% ethyl acetate in hexanes (over 10 column volumes), and held at 100% ethyl acetate for 4 column volumes to provide the title compound as an off-white solid (8 mg, 24%). Mass spectrum (ESI) 656.4 (M+1). 1H NMR (500 MHz, CDCl3):): δ 8.40 (d, J=2.0 Hz, 1H), 8.31 (d, J=8.3 Hz, 2H), 8.25 (d, J=8.7 Hz, 1H), 7.95 (d, J=8.5 Hz, 2H), 7.92 (s, 1H), 7.82 (dd, J=8.7, 2.3 Hz, 1H), 7.51 (s, 1H), 7.40 (m, 4H), 6.82 (t, J=6.3 Hz, 1H), 4.30 (d, J=10.7 Hz, 1H), 4.13 (d, J=10.8 Hz, 1H), 3.94 (dd, J=14.5, 6.3 Hz, 1H), 3.86 (dd, J=14.5, 6.5 Hz, 1H), 3.47 (sept, J=6.9 Hz, 1H), 1.65 (s, 3H), 1.45 (d, J=6.9 Hz, 6H).

Workup

  1. temperatureThe sample was cooled to room temperature
  2. customwas purified via column chromatography on a Biotage Horizon 40M column
  3. washeluting with 0% ethyl acetate in hexanes (1 column volume)

Sources & evidence

ORD record
ord-34be382e94764ecab09eb4e4651b4606
Source dataset
uspto-grants-2012_10
Patent number
US08293721B2

Reaction notes

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