Methanol → HCID 44223284, compound

HRID 2196660Notes

Reaction equation

HRID 2196660 reaction equation
C([O-])(O)=O.[Na+].[C:6](=[S:9])([NH2:8])[CH3:7].Cl[CH2:11][C:12]([C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([NH:23][C:24](=[O:40])[C:25]3[C:30]([F:31])=[CH:29][CH:28]=[C:27]([NH:32][S:33]([CH2:36][CH2:37][CH3:38])(=[O:35])=[O:34])[C:26]=3[F:39])[CH:21]=2)[NH:16][CH:15]=1)=O.CO>C1COCC1>[F:39][C:26]1[C:27]([NH:32][S:33]([CH2:36][CH2:37][CH3:38])(=[O:34])=[O:35])=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[C:24]([NH:23][C:20]1[CH:21]=[C:22]2[C:14]([C:12]3[N:8]=[C:6]([CH3:7])[S:9][CH:11]=3)=[CH:15][NH:16][C:17]2=[N:18][CH:19]=1)=[O:40]

Participants

6

Reactant 4

HCID 887MethanolHCID 516892Sodium Bicarbonate2×HCID 2723949Thioacetamide2×HCID 86653260HCID 86653260, compound

Product 1

HCID 44223284HCID 44223284, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

NaHCO3 (0.00098 g, 0.012 mmol) and ethanethioamide (0.00096 g, 0.013 mmol) were added to N-(3-(2-chloroacetyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (0.005 g, 0.011 mmol) in THF (0.1 mL), and the reaction mixture was warmed to 70° C. for 4 hours. MeOH (0.2 mL) was added, along with another equivalent of ethanethioamide (0.00096 g, 0.013 mmol) and NaHCO3 (0.00098 g, 0.012 mmol). After 9 hours at 70° C., the reaction mixture was cooled and partitioned between EtOAc and aqueous sodium bicarbonate. The organic layers were dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified via column chromatography (10% MeOH-DCM) to provide 2,6-difluoro-N-(3-(2-methylthiazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide (1 mg, 19%). 1H NMR (400 MHz, CHCl3-d1) δ 8.84-8.85 (m, 1H), 7.86 (s, 1H), 7.60-7.66 (m, 1H), 7.32 (s, 1H), 7.02-7.06 (m, 1H), 3.06-3.12 (m, 2H), 2.80 (s, 3H), 1.85-1.93 (m, 2H), 1.04-1.08 (m, 3H); m/z (APCI-pos) M+1=492.1.

Workup

  1. temperaturethe reaction mixture was cooled
  2. custompartitioned between EtOAc and aqueous sodium bicarbonate
  3. dry with materialThe organic layers were dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified via column chromatography (10% MeOH-DCM)

Sources & evidence

ORD record
ord-58dc2dd28cea4638bcc87f9e6e72ee40
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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