Lithium Hydroxide → HCID 71526640, compound

HRID 529734Notes

Reaction equation

HRID 529734 reaction equation
[F:1][C:2]([F:54])([F:53])[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[C:27]([C:28]5[CH:29]=[C:30]([C:36]6[CH:41]=[CH:40][C:39]([C:42]([O:44]C)=[O:43])=[CH:38][C:37]=6[CH3:46])[CH:31]=[CH:32][C:33]=5[O:34][CH3:35])=[CH:26][C:25]([CH:47]([CH3:49])[CH3:48])=[C:24]([N:50]([CH3:52])[CH3:51])[N:23]=4)[CH2:20][CH2:21][C@@H:14]23)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Li+]>C1COCC1>[F:53][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[C:27]([C:28]5[CH:29]=[C:30]([C:36]6[CH:41]=[CH:40][C:39]([C:42]([OH:44])=[O:43])=[CH:38][C:37]=6[CH3:46])[CH:31]=[CH:32][C:33]=5[O:34][CH3:35])=[CH:26][C:25]([CH:47]([CH3:49])[CH3:48])=[C:24]([N:50]([CH3:51])[CH3:52])[N:23]=4)[CH2:20][CH2:21][C@@H:14]23)[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 86682297HCID 86682297, compound

Product 1

HCID 71526640HCID 71526640, compoundYield 36.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To methyl 3′-[2-{(1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-3-oxotetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-5-yl}-6-(dimethylamino)-5-(propan-2-yl)pyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (24 mg, 0.033 mmol) in THF (1 mL) was added lithium hydroxide (9.51 mg, 0.397 mmol). The reaction was stirred overnight at room temperature. Reaction was incomplete. More lithium hydroxide (4.76 mg, 1.99 mmol) was added, and the reaction was heated to 50° C. for 5 hours. The reaction was purified by HPLC to yield 3′-[2-{(1R,5S,7aS)-1-[3,5-bis(trifluoromethyl)phenyl]-3-oxotetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-5-yl}-6-(dimethylamino)-5-(propan-2-yl)pyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylic acid (10 mg, 0.012 mmol). 1H NMR indicated that this compound exists as a pair of rotamers at 1.6:1 ratio. 1H NMR (500 MHz, CDCl3) δ7.94-8.10 (m, 2H), 7.90 (s, 1H), 7.84 (s, 2H), 7.48 (m, 2H), 7.42 (dd, J=8.5 Hz, J=2.0 Hz, 1H), 7.37 (d, J=7.5 Hz, 1H, minor rotamer), 7.30 (d, 1H, merged with solvent peak, major rotamer), 7.14 (d, J=8.5 Hz, 1H, minor rotamer), 7.07 (d, J=8.5 Hz, 1H, major rotamer), 5.98 (d, J=8.0 Hz, 1H, minor rotamer), 5.93 (d, J=8.0 Hz, 1H, major rotamer), 5.09 (t, J=7.5 Hz, 1H, minor rotamer), 5.01 (t, J=7.5 Hz, 1H, major rotamer), 4.76 (m, 1H), 3.93 (s, 3H, minor rotamer), 3.83 (s, 3H, major rotamer), 3.40 (m, 1H), 3.07 (s, 6H), 2.47 (s, 3H, major rotamer), 2.40 (s, 3H, minor rotamer), 2.35 (m, 1H), 2.05 (m, 1H), 1.60 (m, 1H), 1.29 (t, J=6.5 Hz, 6H), 1.08 (m, 1H). MS ESI calc'd. for C39H38F6N3O5 [M+H]+ 742.3, found 742.5. RTA (95% HS): 182 nM

Workup

  1. customReaction
  2. temperaturethe reaction was heated to 50° C. for 5 hours
  3. customThe reaction was purified by HPLC

Sources & evidence

ORD record
ord-6c39aadcb62f44679dd4a5daba46def5
Source dataset
uspto-grants-2016_05
Patent number
US09346825B2

Reaction notes

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