1-Butanol → HCID 59385335, compound

HRID 2356808Notes

Reaction equation

HRID 2356808 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[C:10]([O:18][CH3:19])[CH:9]=2)=[CH:4][CH:3]=1.Cl[C:21]1[S:22][C:23]2[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:24]=2[N:25]=1.Cl.O1CCOCC1.[CH2:38](O)[CH2:39][CH2:40]C>>[F:30][C:28]1[CH:27]=[CH:26][C:24]2[N:25]=[C:21]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([O:16][CH2:17][CH2:38][CH2:39][CH3:40])=[O:15])=[C:10]([O:18][CH3:19])[CH:9]=4)=[CH:6][CH:7]=3)[S:22][C:23]=2[CH:29]=1.[F:30][C:28]1[CH:27]=[CH:26][C:24]2[N:25]=[C:21]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[C:10]([O:18][CH3:19])[CH:9]=4)=[CH:6][CH:7]=3)[S:22][C:23]=2[CH:29]=1

Participants

7

Reactant 5

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 20498702-Chloro-6-fluorobenzothiazoleHCID 59385207HCID 59385207, compound

Product 2

HCID 59385329HCID 59385329, compoundYield 30%HCID 59385335HCID 59385335, compoundYield 44%

Conditions

Temperature
65 °C

Procedure

A mixture of methyl 4′-amino-3-methoxybiphenyl-4-carboxylate (0.27 g, 1.06 mmol) and 2-chloro-6-fluoro-1,3-benzothiazole (0.20 g, 1.06 mmol) in n-butanol (8 mL) was heated to 60-70° C., and then 4N HCl in 1,4-dioxane (0.12 mL, 0.48 mmol) was added dropwise with stirring. The reaction mixture was heated at 90° C. for 18 h. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (25% EtOAc in hexanes), yielding 0.209 g (44%) of butyl 4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-3-methoxybiphenyl-4-carboxylate, and 0.132 g (30%) of methyl 4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-3-methoxybiphenyl-4-carboxylate [LC/MS m/z 409.3 (MH+), retention time=3.67 min, m/z 451.3 (MH+), retention time=4.25 min. 1H NMR (400 MHz, CD2Cl2) δ 3.85 (s, 3H), 4.00 (s, 3H), 7.05-7.26 (m, 3H), 7.42 (d, 1H), 7.61-7.64 (m, 1H), 7.76 (s, 4H), 7.90 (d, 1H)].

Workup

  1. temperatureThe reaction mixture was heated at 90° C. for 18 h
  2. temperatureUpon cooling to rt
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. customThe residue was purified by column chromatography (25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b7d3d388d5554fcab44a8d8d4bf070dd
Source dataset
uspto-grants-2010_07
Patent number
US07759376B2

Reaction notes

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