N-(4-bromo-2-fluorophenyl)-6-fluoro-1,3-benzothiazol-2-amine → CY477Rqr44

HRID 30932

반응식

HRID 30932 반응식
Br[C:2]1[CH:21]=[CH:20][C:5]([C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:7])=[CH:4][CH:3]=1.Br[C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[S:31][C:32]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:33]=3[N:34]=2)=[C:25]([F:40])[CH:24]=1.[F:41][C:42]1[CH:43]=[C:44]([C:63]2[CH:68]=[CH:67][C:66]([C:69]([C@@H:71]3[CH2:75][CH2:74][CH2:73][C@H:72]3[C:76]([O:78]C)=[O:77])=[O:70])=[CH:65][CH:64]=2)[CH:45]=[CH:46][C:47]=1[NH:48][C:49]1[S:50][C:51]2[CH:57]=[C:56](OC(F)(F)F)[CH:55]=[CH:54][C:52]=2[N:53]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[F:40][C:25]1[CH:24]=[C:23]([C:2]2[CH:21]=[CH:20][C:5]([C:6]([C@@H:8]3[CH2:12][CH2:11][CH2:10][C@H:9]3[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:7])=[CH:4][CH:3]=2)[CH:28]=[CH:27][C:26]=1[NH:29][C:30]1[S:31][C:32]2[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:33]=2[N:34]=1.[F:41][C:42]1[CH:43]=[C:44]([C:63]2[CH:64]=[CH:65][C:66]([C:69]([C@@H:71]3[CH2:75][CH2:74][CH2:73][C@H:72]3[C:76]([OH:78])=[O:77])=[O:70])=[CH:67][CH:68]=2)[CH:45]=[CH:46][C:47]=1[NH:48][C:49]1[S:50][C:51]2[CH:57]=[C:56]([F:39])[CH:55]=[CH:54][C:52]=2[N:53]=1

참가 물질

7

반응물 3

HCID 7147089N-(4-bromo-2-fluorophenyl)-6-fluoro-1,3-benzothiazol-2-amineHCID 58681324tert-butyl (1R,2R)-2-(4-bromobenzoyl)-cyclopentanecarboxylateHCID 58681326methyl (1R,2R)-2-[(3'-fluoro-4'-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate

생성물 2

HCID 44464393CY477Rqr44수율 77%HCID 86594966tert-Butyl (1R,2R)-2-({3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매

실험 절차

tert-Butyl (1R,2R)-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate was prepared from tert-butyl (1R,2R)-2-(4-bromobenzoyl)-cyclopentanecarboxylate and N-(4-bromo-2-fluorophenyl)-N-(6-fluoro-1,3-benzothiazol-2-yl)amine in a similar manner to that described above for methyl (1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate. A solution of the tert-butyl ester (1.5 g, 2.81 mmol) in 2.0 mL TFA and 10 mL CH2Cl2 was stirred at rt overnight. After the solvent was removed by rotary evaporation, 50 mL EtOAc and 50 mL water were added. The organic layer was separated, washed with 50 mL water, and then dried over Na2SO4. After the solvent was removed by rotary evaporation, 5 mL EtOAc was added to the residue, followed by 5 mL hexanes. The precipitate that formed was collected by filtration to afford the desired product as a light yellow solid (1.0 g, 77%, 95.2% ee). 1H NMR (400 MHz, DMSO-d6) δ 12.20 (br s, 1H), 10.50 (bs, 1H), 8.70 (t, 1H), 7.60-8.10 (m, 8H), 7.20 (t, 1H), 4.10 (m, 1H), 3.20 (m, 1H), 2.20 (m, 1H), 2.00 (m, 1H), 1.50-1.90 (m, 4H); LC-MS m/z 479.3 (MH+), ret. time 3.64 min.

후처리

  1. customAfter the solvent was removed by rotary evaporation, 50 mL EtOAc and 50 mL water
  2. additionwere added
  3. customThe organic layer was separated
  4. washwashed with 50 mL water
  5. dry with materialdried over Na2SO4
  6. customAfter the solvent was removed by rotary evaporation, 5 mL EtOAc
  7. additionwas added to the residue
  8. customThe precipitate that formed
  9. filtrationwas collected by filtration

출처 및 근거

ORD 기록
ord-aa6d0ccdfde94e1493658dac063d5e08
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423156B2

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