Sulfuric Acid → N-[2-({6-[2-Amino-1-(2,6-dichlorophenyl)-2-oxoethyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide

HRID 2096250Notes

Reaction equation

HRID 2096250 reaction equation
[C:1]([CH:3]([C:34]1[C:39]([Cl:40])=[CH:38][CH:37]=[CH:36][C:35]=1[Cl:41])[C:4]1[N:9]=[N:8][C:7]([S:10][C:11]2[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=2[CH2:13][NH:14][C:15](=[O:29])[C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:19]=[C:18]([F:28])[CH:17]=2)=[CH:6][CH:5]=1)#[N:2].S(=O)(=O)(O)[OH:43]>>[NH2:2][C:1](=[O:43])[CH:3]([C:4]1[N:9]=[N:8][C:7]([S:10][C:11]2[CH:33]=[CH:32][CH:31]=[CH:30][C:12]=2[CH2:13][NH:14][C:15](=[O:29])[C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:19]=[C:18]([F:28])[CH:17]=2)=[CH:6][CH:5]=1)[C:34]1[C:35]([Cl:41])=[CH:36][CH:37]=[CH:38][C:39]=1[Cl:40]

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 66822461N-[2-({6-[Cyano(2,6-dichlorophenyl)methyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide

Product 1

HCID 46861613N-[2-({6-[2-Amino-1-(2,6-dichlorophenyl)-2-oxoethyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamideYield 67%

Conditions

Temperature
70 °C

Procedure

N-[2-({6-[Cyano(2,6-dichlorophenyl)methyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide (92 mg, 0.15 mmol) was treated with concentrated sulfuric acid (2 mL) and the mixture was stirred at 70° C. for 30 min. The solution was cooled to RT, quenched with ice-water and extracted into DCM. The organic layer was washed with aqueous saturated NaHCO3, dried over MgSO4, filtered, and the filtrate was concentrated in vacuo. Purification by flash column chromatography (DCM:MeOH from 97.3:2.7 to 95:5) afforded the title compound (63 mg, 67%) which co-exists in solution as a mixture of the amide and the enol-amine. LCMS (Method 3): Rt 10.15 & 11.27 min, m/z 626 [MH−]. 1H NMR (400 MHz, CD3OD) (ratio amide/enol-amine 1:0.8): 7.65 (1H, dd, J 7.6, 1.2), 7.57-7.43 (5.4H, m), 7.42-7.37 (3.6H, m), 7.36-7.29 (3.6H, m), 7.21 (0.8H, t, J 1.8), 7.17-7.13 (2H, m), 6.99 (0.8H, ddd, J 9, 2.3, 1.4), 6.95-6.93 (1H, m), 6.85-6.80 (1.8H, m), 6.58 (0.8H, d, J 9.9), 6.15 (0.8H, d, J 9.9), 5.98 (1H, s), 4.73 (1.6H, s), 4.71 (2H, d, J 1.8), 3.82 (7.2H, t, J 4.8), 3.22-3.17 (7.2H, m).

Workup

  1. temperatureThe solution was cooled to RT
  2. customquenched with ice-water
  3. extractionextracted into DCM
  4. washThe organic layer was washed with aqueous saturated NaHCO3
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification by flash column chromatography (DCM:MeOH from 97.3:2.7 to 95:5)

Sources & evidence

ORD record
ord-774a98110f6344b29d3c3351f617d2f0
Source dataset
uspto-grants-2013_05
Patent number
US08450314B2

Reaction notes

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