Water → 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-4-(4-fluorophenyl)-4,5-dihydrobenzo[d]thiazol-6(7H)-one

HRID 1803272Notes

Reaction equation

HRID 1803272 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[S:15][C:16]4[CH2:26][C:21]5([O:25][CH2:24][CH2:23][O:22]5)[CH2:20][CH:19]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:17]=4[N:18]=3)=[CH:9][C:8]=2[O:34][CH3:35])[CH:6]=1.O>CC(C)=O>[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[S:15][C:16]4[CH2:26][C:21](=[O:22])[CH2:20][CH:19]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:17]=4[N:18]=3)=[CH:9][C:8]=2[O:34][CH3:35])[CH:6]=1.[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[S:15][C:16]4[CH2:26][C:21]([O:22][CH3:23])([O:25][CH3:24])[CH2:20][CH:19]([C:27]5[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=5)[C:17]=4[N:18]=3)=[CH:9][C:8]=2[O:34][CH3:35])[CH:6]=1

Participants

5

Reactant 2

HCID 962WaterHCID 46864555N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-5,7-dihydro-4H-spiro[benzo[d]thiazole-6,2'-[1,3]dioxolan]-2-amine

Product 2

HCID 581100012-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-4-(4-fluorophenyl)-4,5-dihydrobenzo[d]thiazol-6(7H)-oneYield 47%HCID 58110090N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-6,6-dimethoxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-amineYield 19%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-5,7-dihydro-4H-spiro[benzo[d]thiazole-6,2′-[1,3]dioxolan]-2-amine (569 mg, 1.109 mmol) in acetone (7.9 mL)/water (1.6 mL)/70% HClO4 (1.6 mL) was stirred at 50° C. overnight. The crude product was purified using preparatory HPLC (Column: Phenomenex Luna C18 30×100 mm, Solvent A=10 mM ammonium acetate in 95:5 water/ACN, Solvent B=10 mM Ammonium Acetate in 5:95 water/ACN. Flow rate: 40 ml/min, 30-100% B, 15 min) to afford 273 mg (47% yield) of 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-4-(4-fluorophenyl)-4,5-dihydrobenzo[d]thiazol-6(7H)-one and 120 mg (19% yield) of the titled compound as a yellow solid. Data for example 83: LC-MS (M+H)+ 515.2. 1H NMR (400 MHz, methanol-d4) δ ppm 7.82 (d, J=2.27 Hz, 1 H) 7.64 (d, J=1.51 Hz, 1 H) 7.19-7.27 (m, 2 H) 7.18 (d, J=1.51 Hz, 1 H) 7.13 (d, J=8.56 Hz, 1H) 6.96-7.06 (m, 2 H) 6.66 (dd, J=8.56, 2.27 Hz, 1 H) 3.95-4.05 (m, 1 H) 3.33 (s, 3H) 3.31 (s, 3 H) 3.25 (s, 3 H) 3.12 (dt, J=16.12, 2.01 Hz, 1 H) 2.92 (dd, J=16.12, 3.02 Hz, 1 H) 2.48 (ddd, J=13.79, 5.73, 2.39 Hz, 1H).

Workup

  1. customThe crude product was purified
  2. customHPLC (Column: Phenomenex Luna C18 30×100 mm, Solvent A=10 mM ammonium acetate in 95:5 water/ACN, Solvent B=10 mM Ammonium Acetate in 5:95 water/ACN. Flow rate: 40 ml/min, 30-100% B, 15 min)

Sources & evidence

ORD record
ord-24a7511d762d4de3934ddfb75b4fd880
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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