Sodium hydride → HCID 71557024, compound

HRID 2203431Notes

Reaction equation

HRID 2203431 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[OH:18].[H-].[Na+].COC1C=C(OC)C=CC=1C[N:26]([C:39]1[S:43][N:42]=[CH:41][N:40]=1)[S:27]([C:30]1[CH:35]=[C:34]([F:36])[C:33](F)=[CH:32][C:31]=1[F:38])(=[O:29])=[O:28]>CN(C)C=O.ClCCl.FC(F)(F)C(O)=O>[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[O:18][C:33]1[C:34]([F:36])=[CH:35][C:30]([S:27]([NH:26][C:39]2[S:43][N:42]=[CH:41][N:40]=2)(=[O:28])=[O:29])=[C:31]([F:38])[CH:32]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 59436583N-(2,4-Dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 89544350HCID 89544350, compound

Product 1

HCID 71557024HCID 71557024, compoundYield 17%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 2-(6-amino-9H-purin-9-yl)-4-chlorophenol (0.053 g, 0.2 mmol) in N,N-dimethylformamide (1 mL) was added sodium hydride (60% w/w dispersion in mineral oil, 0.009 g, 0.2 mmol) and the mixture was stirred for 1 h at ambient temperature. N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.107 g, 0.24 mmol) was added and the mixture was stirred at ambient temperature for 16 h and partitioned between ethyl acetate (100 mL) and saturated aqueous ammonium chloride (20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue obtained was dissolved in dichloromethane (3 mL) and trifluoroacetic acid (3 mL). The reaction mixture was stirred for 1 h at ambient temperature and concentrated in vacuo. The residue was purified by preparative reverse-phase HPLC to afford 4-(2-(6-amino-9H-purin-9-yl)-4-chlorophenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as an off-white solid in 17% yield (0.018 g): 1H NMR (300 MHz, DMSO-d6) δ8.48 (br s, 1H), 8.39 (s, 1H), 8.17 (br s, 1H), 7.95-7.74 (m, 4H), 7.74-7.58 (m, 2H), 7.40 (d, J=8.4 Hz, 1H), 7.34-7.22 (m, 1H); MS (ES+) m/z 536.6 (M+1), 538.6 (M+1).

Workup

  1. stirringthe mixture was stirred at ambient temperature for 16 h
  2. custompartitioned between ethyl acetate (100 mL) and saturated aqueous ammonium chloride (20 mL)
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. stirringThe reaction mixture was stirred for 1 h at ambient temperature
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-882689c2357b4059bc055524ad211544
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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