HCID 86682296, compound → HCID 71526553, compound

HRID 540472Notes

Reaction equation

HRID 540472 reaction equation
[F:1][C:2]([F:55])([F:54])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]3[C@H:19]([C:22]4[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=4[C:32]4[CH:33]=[C:34]([C:40]5[CH:52]=[CH:51][C:43]([C:44]([O:46]C(C)(C)C)=[O:45])=[CH:42][C:41]=5[CH3:53])[CH:35]=[N:36][C:37]=4[O:38][CH3:39])[CH2:20][CH2:21][C@@H:14]23)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1>ClCCl.C(O)(C(F)(F)F)=O>[F:55][C:2]([F:1])([F:54])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]3[C@H:19]([C:22]4[CH:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=[CH:24][C:23]=4[C:32]4[CH:33]=[C:34]([C:40]5[CH:52]=[CH:51][C:43]([C:44]([OH:46])=[O:45])=[CH:42][C:41]=5[CH3:53])[CH:35]=[N:36][C:37]=4[O:38][CH3:39])[CH2:20][CH2:21][C@@H:14]23)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

3

Reactant 1

HCID 86682296HCID 86682296, compound

Product 1

HCID 71526553HCID 71526553, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

To tert-butyl 4-{5-[2-{(1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-3-oxotetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-5-yl}-4-(trifluoromethyl)phenyl]-6-methoxypyridin-3-yl}-3-methylbenzoate (1 g, 1.28 mmol) was added dichloromethane:TFA (9:1, 10 mL). The reaction was stirred overnight at room temperature. Upon completion the solvent was removed under reduced pressure and the resultant residue was redissolved in acetonitrile for direct purification by reverse phase HPLC to yield 4-{5-[2-{(1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-3-oxotetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-5-yl}-4-(trifluoromethyl)phenyl]-6-methoxypyridin-3-yl}-3-methylbenzoic acid (0.674 g, 0.931 mmol). 1H NMR indicated that this compound exists as a pair of rotamers at 1.2:1 ratio. 1H NMR (500 MHz, CDCl3) δ8.27 (s, 1H), 8.04 (m, 4H, peaks overlap for the two rotamers), 7.90 (s, 1H), 7.84 (s, 2H, minor rotamer), 7.83 (s, 2H, major rotamer), 7.75 (s, 1H, major rotamer), 7.67 (s, 1H, minor rotamer), 7.63 (d, J=8 Hz, 1H, major rotamer), 7.42 (m, 2H), 7.38 (d, J=7.9 Hz, 1H, major rotamer), 7.36 (d, J=7.9 Hz, 1H, minor rotamer), 6.11 (d, J=7.9 Hz, 1H, minor rotamer), 6.09 (d, J=7.9 Hz, 1H, major rotamer), 5.27 (t, J=7.9 Hz, 1H, major rotamer), 4.95 (t, J=7.9 Hz, 1H, minor rotamer), 4.62 (m, 1H, minor rotamer), 4.51 (m, 1H, major rotamer), 4.12 (s, 3H, minor rotamer), 3.94 (s, 3H, minor rotamer), 2.45 (s, 3H, minor rotamer), 2.45 (s, 3H, major rotamer), 2.37 (m, 1H), 2.2 (m, 1H), 2.05 (m, 1H), 1.85 (m, 1H), 1.55 (m, 1H), 1.4 (m, 1H), 1.1 (m, 2H). MS ESI calc'd. for C35H26F9N2O5 [M+H]+ 725.2. found 725.0. RTA (95% HS): 53.18 nM

Workup

  1. customUpon completion the solvent was removed under reduced pressure
  2. dissolutionthe resultant residue was redissolved in acetonitrile for direct purification by reverse phase HPLC

Sources & evidence

ORD record
ord-134fff0461d342718ee1f705707b426b
Source dataset
uspto-grants-2014_10
Patent number
US08871738B2

Reaction notes

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