Pyridine → 4-(2-Fluorophenyl)-7-(methylsulfonamido)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361265Notes

Reaction equation

HRID 2361265 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[F:21])=[CH:13][N:12]=[C:11]([C:22]([NH2:24])=[O:23])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1.[CH3:25][S:26](Cl)(=[O:28])=[O:27].N1C=CC=CC=1>ClCCl>[F:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:14]1[C:6]2[C:5]3[C:9](=[CH:10][C:2]([NH:1][S:26]([CH3:25])(=[O:28])=[O:27])=[CH:3][CH:4]=3)[NH:8][C:7]=2[C:11]([C:22]([NH2:24])=[O:23])=[N:12][CH:13]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 679945367-amino-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

Product 1

HCID 547665644-(2-Fluorophenyl)-7-(methylsulfonamido)-9H-pyrido[3,4-b]indole-1-carboxamideYield 15.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-amino-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (25 mg, 0.078 mmol) in dichloromethane (2 mL) at rt was sequentially added methanesulfonyl chloride (22.35 mg, 0.195 mmol) and pyridine (0.016 mL, 0.195 mmol). The mixture was stirred at room temperature for 1 hr and then at 50° C. in a closed vial for 30 min. The mixture was concentrated. The residue was diluted with MeOH (1.5 mL) and subjected to prep. reverse phase HPLC purification. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution to pH 9, and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with brine (25 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (4.81 mg, 0.012 mmol, 15.00% yield) as a pale solid. LCMS (M+H)+=399.03. 1H NMR (500 MHz, DMSO-d6) δ: 11.85 (s, 1H), 10.03 (s, 1H), 8.30 (s, 1H), 8.23 (s, 1H), 7.77 (s, 1H), 7.75 (s, 1H), 7.67-7.63 (m, 2H), 7.50-7.43 (m, 2H), 7.19 (d, J=7.7 Hz, 1H), 6.92 (dd, J1=8.8 Hz, J2=2.2 Hz, 1H), 3.02 (s, 3H).

Workup

  1. customat rt
  2. waitat 50° C. in a closed vial for 30 min
  3. concentrationThe mixture was concentrated
  4. additionThe residue was diluted with MeOH (1.5 mL)
  5. customphase HPLC purification
  6. concentrationThe correct fraction was concentrated under vacuum
  7. extractionextracted with ethyl acetate (3×30 mL)
  8. washThe combined extracts were washed with brine (25 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-08fc264d33314b05b5ccb598408cb97f
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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