Sodium hydride → 6-(2-fluorophenyl)-3-[5-(4-methoxy-2-trifluoromethylphenyl)-[1,3,4]thiadiazol-2-ylmethyl]-3H-pyrrolo[3,2-d]pyrimidine-7-carbonitrile

HRID 2408485Notes

Reaction equation

HRID 2408485 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:16][C:15]2[CH:14]=[N:13][CH:12]=[N:11][C:10]=2[C:9]=1[C:17]#[N:18].[CH3:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[S:31][C:30]([CH2:32]OS(C)(=O)=O)=[N:29][N:28]=2)=[C:23]([C:38]([F:41])([F:40])[F:39])[CH:22]=1.[H-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:17]#[N:18])=[C:10]2[C:15]([N:16]=1)=[CH:14][N:13]([CH2:32][C:30]1[S:31][C:27]([C:24]3[CH:25]=[CH:26][C:21]([O:20][CH3:19])=[CH:22][C:23]=3[C:38]([F:41])([F:39])[F:40])=[N:28][N:29]=1)[CH:12]=[N:11]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 674703166-(2-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbonitrileHCID 86688860Methanesulfonic acid 5-(4-methoxy-2-trifluoromethylphenyl)-[1,3,4]thiadiazol-2-ylmethyl ester

Product 1

HCID 547603136-(2-fluorophenyl)-3-[5-(4-methoxy-2-trifluoromethylphenyl)-[1,3,4]thiadiazol-2-ylmethyl]-3H-pyrrolo[3,2-d]pyrimidine-7-carbonitrileYield 8.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(2-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbonitrile (29 mg) and methanesulfonic acid 5-(4-methoxy-2-trifluoromethylphenyl)-[1,3,4]thiadiazol-2-ylmethyl ester (49 mg) in DMF was added NaH (5 mg). The reaction was stirred for 14 h at rt. The reaction was quenched by slow addition of AcOH (glacial), filtered, and purified by HPLC (10-70% MeCN/H2O with 1% formic acid) then lyophilized to give 5.3 mg of the titled compound (8%). 1H NMR (DMSO-d6): 9.40 (s, 1 h), 9.18 (s, 1 h), 7.85 (t, 1 h), 7.73 (d, 1H), 7.56-7.64 (m, 1H), 7.35-7.47 (m, 4H), 6.30 (s, 2H), 3.93 (s, 3H). LC-MS calculated for C24H14F4N6OS 510.5, found 511.00 [M+H]+.

Workup

  1. customThe reaction was quenched by slow addition of AcOH (glacial)
  2. filtrationfiltered
  3. custompurified by HPLC (10-70% MeCN/H2O with 1% formic acid)

Sources & evidence

ORD record
ord-8d4eb6ab083943dd8b5e03e7e72c61d4
Source dataset
uspto-grants-2014_08
Patent number
US08815858B2

Reaction notes

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