Pyridine → HCID 57989786, compound

HRID 1962030Notes

Reaction equation

HRID 1962030 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7]([O-:9])=[O:8].[Na+].ClN1C(=O)CCC1=O.S(Cl)(Cl)(=O)=O.[NH2:24][C:25]1[C:26]([F:47])=[C:27]([C:31]2[N:32]=[C:33]([C:43]([CH3:46])([CH3:45])[CH3:44])[S:34][C:35]=2[C:36]2[CH:41]=[CH:40][N:39]=[C:38]([NH2:42])[N:37]=2)[CH:28]=[CH:29][CH:30]=1.N1C=CC=CC=1>ClCCl>[NH2:42][C:38]1[N:37]=[C:36]([C:35]2[S:34][C:33]([C:43]([CH3:45])([CH3:46])[CH3:44])=[N:32][C:31]=2[C:27]2[C:26]([F:47])=[C:25]([NH:24][S:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)(=[O:9])=[O:8])[CH:30]=[CH:29][CH:28]=2)[CH:41]=[CH:40][N:39]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 24648Sulfuryl chlorideHCID 31398ChlorosuccinimideHCID 23678794Sodium Pyridine-2-sulfinateHCID 579897094-[4-(3-Amino-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinamine

Product 1

HCID 57989786HCID 57989786, compoundYield 12.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of sodium 2-pyridinesulfinate (48.4 mg, 0.291 mmol) in dichloromethane (3 ml) was added N-chlorosuccinimide (38.9 mg, 0.291 mmol). After 1 hour, the reaction mixture was filtered through a short Celite plug. To the crude sulfonyl chloride solution was added the 4-[4-(3-amino-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinamine (50 mg, 0.146 mmol) and pyridine (0.035 ml, 0.437 mmol), and the mixture was stirred for 3 hours at ambient temperature. After 3 hours, the reaction was quenched with methanol, and the crude reaction mixture was concentrated, redissolved in methanol, and purified via reversed-phase HPLC chromatography, eluting with 30-60% acetonitrile/0.1% aqueous trifluoroacetic acid. The desired fractions were combined, neutralized with aqueous saturated sodium bicarbonate, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the title compound (8.8 mg, 12%) as tan solid. MS (ESI): 485 [M+H]+.

Workup

  1. filtrationthe reaction mixture was filtered through a short Celite plug
  2. waitAfter 3 hours
  3. customthe reaction was quenched with methanol
  4. customthe crude reaction mixture
  5. concentrationwas concentrated
  6. dissolutionredissolved in methanol
  7. custompurified via reversed-phase HPLC chromatography
  8. washeluting with 30-60% acetonitrile/0.1% aqueous trifluoroacetic acid
  9. extractionextracted with ethyl acetate
  10. washThe organic layer was washed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-c2699b7d070f4d41b51dbf1d78f9c345
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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