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

HRID 907755

Reaktionsgleichung

Reaktionsgleichung von HRID 907755
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

Komponenten

7

Edukt 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

Produkt 2

HCID 44464393CY477Rqr44Ausbeute 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-8b604805b1bb4eb1b511758833a4c10f
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08013166B2

Verknüpfte Notizen

Wird geladen…