Phosgene → HCID 71526641, compound

HRID 540476Notes

Reaction equation

HRID 540476 reaction equation
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@@H:13]2[C@@H:17]3[CH2:18][CH2:19][CH2:20][C@@H:21]([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[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[C:34]([CH2:40][CH2:41][C:42]([NH:44][NH2:45])=[O:43])[CH:33]=4)[N:16]3[C:15](=[O:46])[O:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCN(C(C)C)C(C)C.[C:58](Cl)(Cl)=[O:59]>C(Cl)Cl>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[C:5]([C@@H:13]2[C@@H:17]3[CH2:18][CH2:19][CH2:20][C@@H:21]([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]([CH2:40][CH2:41][C:42]5[O:43][C:58](=[O:59])[NH:45][N:44]=5)[CH:35]=[CH:36][C:37]=4[O:38][CH3:39])[N:16]3[C:15](=[O:46])[O:14]2)[CH:4]=[C:3]([C:2]([F:1])([F:47])[F:48])[CH:8]=1

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 86682298HCID 86682298, compound

Product 1

HCID 71526641HCID 71526641, compoundYield 46,600%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3-[2′-{(1R,5S,8aS)-1-[3,5-bis(trifluoromethyl)phenyl]-3-oxohexahydro[1,3]oxazolo[3,4-a]pyridin-5-yl}-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]propanehydrazide (10 mg, 0.015 mmol) in DCM (2 mL) was added DIPEA (5.6 mg, 0.044 mmol) and phosgene (4.30 mg, 0.44 mmol). The reaction was stirred at room temperature for 30 minutes before the reaction was directly purified by column chromatography to yield (1R,5S,8aS)-1-[3,5-bis(trifluoromethyl)phenyl]-5-{2′-methoxy-5′-[2-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)ethyl]-4-(trifluoromethyl)biphenyl-2-yl}hexahydro[1,3]oxazolo[3,4-a]pyridin-3-one (5 mg, 6.99 mmol). 1H NMR indicated that this compound exists as a pair of rotamers at 3:1 ratio: 1H NMR (500 MHz, CDCl3) δ9.23 (s, 1H), 7.88 (s, 1H), 7.80 (s, 2H), 7.79 (s, 1H, minor rotamer), 7.65 (s, 2H, major rotamer) 7.62 (m, 1H) 7.4 (d, J=7.8 Hz, 1H, major rotamer), 7.25 (d, J=7.8 Hz, 1H, minor rotamer), 7.09 (s, 1H), 7.02 (m, 2H), 5.58 (m, 1H, minor rotamer) 5.42 (m, 1H, major rotamer), 4.19 (m, 1H), 3.85 (s, 3H, minor rotamer), 3.80 (s, 3H, major rotamer), 3.0-2.85 (m, 4H), 1.98 (m, 2H), 1.5-1.6 (m, 4H). MS ESI calc'd. for C33H27F9N3O5 [M+H]+ 716.2. found 716.3. RTA (95% HS): 942 nM

Workup

  1. customwas directly purified by column chromatography

Sources & evidence

ORD record
ord-c07f20dca36a442aacfe5fbe5d19d6b8
Source dataset
uspto-grants-2014_10
Patent number
US08871738B2

Reaction notes

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