Nitrogen → 2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-fluoro-5'-isopropyl-2'-methoxybiphenyl-4-carbonitrile

HRID 1028665노트

반응식

HRID 1028665 반응식
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24](Br)[CH:23]=[CH:22][C:21]=3[C:27]3[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=3[O:37][CH3:38])[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Cu][C:43]#[N:44].N#N>CN(C)C=O>[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:43]#[N:44])[CH:23]=[CH:22][C:21]=3[C:27]3[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=3[O:37][CH3:38])[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

참가 물질

5

반응물 3

HCID 947NitrogenHCID 11556473(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl)-3-[(4-bromo-4'-fluoro-5'-isopropyl-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-oneHCID 178418546HCID 178418546, 화합물

생성물 1

HCID 117069992-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-fluoro-5'-isopropyl-2'-methoxybiphenyl-4-carbonitrile

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-bromo-4′-fluoro-5′-isopropyl-2′-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (100 mg, 0.15 mmol) in N,N-dimethylformamide (1.5 mL) was added copper(I) cyanide (17 mg, 0.19 mmol). The resulting reaction mixture was N2 purged and sealed in a microwave vessel. The vessel was subject to microwave irradiation at 150° C. for 30 min. LC-MS indicated only the starting bromide was present. Added tetrakis(triphenylphosphine)palladium(0) (10 mg, 6 mol %) into the reaction mixture. Repeated microwave irradiation at 150° C. for 30 min. An aliquot indicated the desired product was formed and all starting bromide was consumed. Reaction crude was partitioned between water and hexanes. The aqueous phase was back extracted with diethyl ether. The combined extracts were dried over Na2SO4. The titled compound was obtained as a glassy material after two preparative TLC plates developed respectively by 20% EtOAc in hexanes and 4% EtOAc in dichloromethane. LC-MS: 595.03 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 1:1 mixture of rotamers δ 7.86 (s, 1 H), 7.61 (S, 0.5 H), 7.67-7.71 (m, 2.5H), 7.64-7.68 (m, 1 H), 7.32-7.36 (m, 1 H), 6.98 (d, J=8.5 Hz, 0.5H), 6.95 (d, J=8.5 Hz, 0.5 H), 6.68 (d, J=12 Hz, 1H), 5.62 (d, J=8.0 Hz, 0.5H), 5.46 (d, J=8.0 Hz, 0.5H), 4.85 (d, J=16.0 Hz, 0.5H), 4.80 (d, J=16.0 Hz, 0.5 H), 4.06 (d, J=16 Hz, 0.5 H), 3.79-3.86 (m, 1 H), 3.70-3.78 (m, 3.5 H), 3.16-3.24 (m, 1H), 3.75 (s, 1.5 H), 3.16-3.25 (m, 1H), 3.14 (s, 1.5 H), 3.13 (s, 1.5 H), 1.15-1.27 (m, 6 H), 0.54 (d, J=7.0 Hz, 1.5 H), 0.37 (d, J=6.5 Hz, 1.5 H).

후처리

  1. customThe resulting reaction mixture
  2. custompurged
  3. customsealed in a microwave vessel
  4. customirradiation at 150° C. for 30 min
  5. custommicrowave irradiation at 150° C. for 30 min
  6. customwas formed
  7. customall starting bromide was consumed
  8. customReaction crude
  9. customwas partitioned between water and hexanes
  10. extractionThe aqueous phase was back extracted with diethyl ether
  11. dry with materialThe combined extracts were dried over Na2SO4

출처 및 근거

ORD 기록
ord-51faebf194384d9787179563fbab20c6
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735435B2

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