1-Butanol → butyl (1R,2R)-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-2-yl)-amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate

HRID 9597Notes

Reaction equation

HRID 9597 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([C@@H:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[C:21]([O:23][CH3:24])=[O:22])=[O:15])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[F:25].[CH3:26][O:27][C:28]1[CH:40]=[CH:39][C:31]2[N:32]=[C:33](S(C)(=O)=O)[S:34][C:30]=2[CH:29]=1.Cl.[CH2:42](O)[CH2:43][CH2:44]C>>[F:25][C:3]1[CH:4]=[C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([C@@H:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[C:21]([O:23][CH2:24][CH2:42][CH2:43][CH3:44])=[O:22])=[O:15])=[CH:12][CH:13]=2)[CH:6]=[CH:7][C:2]=1[NH:1][C:33]1[S:34][C:30]2[CH:29]=[C:28]([O:27][CH3:26])[CH:40]=[CH:39][C:31]=2[N:32]=1

Participants

5

Reactant 4

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 219858516-Methoxy-2-(methylsulfonyl)-1,3-benzothiazole2×HCID 58681300Methyl (1R,2R)-2-[(4'-amino-3'-fluoro-1,1'-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate

Product 1

HCID 58681321butyl (1R,2R)-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-2-yl)-amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylateYield 65%

Conditions

Temperature
90 °C

Procedure

Methyl (1R,2R)-2-[(4′-amino-3′-fluoro-1,1′-biphenyl-4-yl)carbonyl]cyclo-pentanecarboxylate (462 mg, 1.35 mmol) was dissolved in n-butanol (15 mL), and 6-methoxy-2-(methylsulfonyl)-1,3-benzothiazole (162 mg, 0.8 mmol) and 4 M aqueous HCl (1.5 mL) were added. The mixture was heated at 90° C. for 5 h. An additional portion of 6-methoxy-2-(methylsulfonyl)-1,3-benzothiazole (162 mg, 0.8 mmol) was added, and the mixture was stirred overnight at 90° C. Solvent was then removed by rotary evaporation, and the residue was purified by flash chromatography (Biotage Flash 40 M, 3:1 hexane/EtOAc) to afford butyl (1R,2R)-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate (480 mg, 65%). LC-MS ret. time 4.36 min, m/z 547.3 (MH+); 1H NMR (300 MHz, CDCl3) δ 0.85 (t, 3H), 1.25–1.35 (m, 2H), 1.40–1.58 (m, 2H), 1.74–1.84 (m, 3H), 1.91–1.96 (m, 1H), 2.11-2.20 (m, 2H), 3.40–3.46 (m, 1H), 3.84 (s, 3H), 4.03 (t, 2H), 6.81–6.87 (m, 1H), 6.98 (dd, 1H), 7.18 (d, 1H), 7.40–7.52 (m, 2H), 7.64 (d, 2H), 8.14 (d, 2H), 8.42 (t, 1H).

Workup

  1. customSolvent was then removed by rotary evaporation
  2. customthe residue was purified by flash chromatography (Biotage Flash 40 M, 3:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-91db071b1f494ddaa49f96c7422a9c42
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

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