Hydrochloric Acid → N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine

HRID 1803266Notes

Reaction equation

HRID 1803266 reaction equation
C([O-])(=O)C.[NH4+:5].[BH4-].[Na+].[Cl:8][C:9]1[N:10]=[CH:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[S:22][C:23]4[CH2:29][C:28](=O)[CH2:27][CH:26]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[C:24]=4[N:25]=3)=[CH:16][C:15]=2[O:38][CH3:39])[CH:13]=1.Cl.[BH4-]>CO>[Cl:8][C:9]1[N:10]=[CH:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[S:22][C:23]4[CH2:29][CH:28]([NH2:5])[CH2:27][CH:26]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[C:24]=4[N:25]=3)=[CH:16][C:15]=2[O:38][CH3:39])[CH:13]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 28123BorohydrideHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 581100012-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-4-(4-fluorophenyl)-4,5-dihydrobenzo[d]thiazol-6(7H)-one

Product 1

HCID 58110003N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamineYield 37.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

Ammonium acetate (123 mg, 1.599 mmol) and sodium borohydride (46.9 mg, 0.746 mmol) were added to a solution of 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-4-(4-fluorophenyl)-4,5-dihydrobenzo[d]thiazol-6(7H)-one (50 mg, 0.107 mmol, from example 75) in MeOH (1.1 mL). The mixture was heated at 65° C. for 20 hours. Several drops of aqueous 1 M HCl were added to the reaction mixture to decompose the excess borohydride reagent. The solvent was removed in vacuo. The residue was made basic with 1N NaOH solution and extracted with dichloromethane. 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, 30-80% B, 18 min) to afford N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (21 mg, 0.040 mmol, 37.7% yield) as a white solid. LC-MS (M+H)+ 470.2. 1H NMR (400 MHz, methanol-d4) δ ppm 7.82 (d, J=2.52 Hz, 1 H) 7.63 (d, J=1.51 Hz, 1H) 7.33 (s, 1 H) 7.17-7.24 (m, 3 H) 7.13 (d, J=8.56 Hz, 1 H) 6.97-7.06 (m, 2 H) 6.64 (dd, J=8.56, 2.27 Hz, 1H) 4.00-4.23 (m, 3H) 3.31 (s, 3 H) 2.99-3.09 (m, 1 H) 2.70 (ddd, J=15.23, 9.69, 3.27 Hz, 1 H) 2.30-2.41 (m, 1 H).

Workup

  1. customThe solvent was removed in vacuo
  2. extractionextracted with dichloromethane
  3. customThe crude product was purified
  4. 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, 30-80% B, 18 min)

Sources & evidence

ORD record
ord-2b1086e4677d4cd7bcd8f60761d2a780
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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