5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chloride → HCID 10258200, compound

HRID 858041Notes

Reaction equation

HRID 858041 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C:7]2[NH:15][C:14]3[C:13](=[O:16])[N:12]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[F:24])[C:11](=[O:25])[N:10]([CH2:26][CH:27]4[CH2:29][CH2:28]4)[C:9]=3[N:8]=2)=[CH:4][CH:3]=1.[Cl:32][C:33]1[N:37]([CH3:38])[N:36]=[C:35]([CH3:39])[C:34]=1[S:40](Cl)(=[O:42])=[O:41]>N1C=CC=CC=1.C(Cl)Cl>[CH:27]1([CH2:26][N:10]2[C:9]3[N:8]=[C:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([NH:1][S:40]([C:34]5[C:35]([CH3:39])=[N:36][N:37]([CH3:38])[C:33]=5[Cl:32])(=[O:41])=[O:42])=[CH:31][CH:30]=4)[NH:15][C:14]=3[C:13](=[O:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:11]2=[O:25])[CH2:28][CH2:29]1

Participants

5

Reactant 2

HCID 27771265-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chlorideHCID 218917373-Cyclopropylmethyl-8-[4-aminobenzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione

Product 1

HCID 10258200HCID 10258200, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 8-(4-amino-benzyl)-3-cyclopropylmethyl-1-(2-fluoro-benzyl)-3,7-dihydro-purine-2,6-dione (2.0 g, 4.77 mmol) in pyridine (30 mL) under argon at 25° C. was treated with 5-chloro-1,3-dimethyl-pyrazole-4-sulfonyl chloride (1.31 g, 5.72 mmol). The reaction mixture was stirred at 25° C. for 24 h. The reaction mixture was then diluted with methylene chloride (500 mL) and washed with a 1.0N aqueous hydrochloric acid solution (3×100 mL). The combined water layers were extracted with methylene chloride (1×250 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was stirred in acetonitrile (25 mL) for 20 min and then placed in the freezer for 1 h. The solids were collected by filtration, washed with cold acetonitrile, and dried in vacuo to afford 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-amide (2.53 g, 87%) as a yellow solid; FAB-HRMS m/e calculated for C28H27ClFN7O4S (M+H)+ 612.1596, found 612.1585.

Workup

  1. washwashed with a 1.0N aqueous hydrochloric acid solution (3×100 mL)
  2. extractionThe combined water layers were extracted with methylene chloride (1×250 mL)
  3. washThe combined organics were washed with a saturated aqueous sodium chloride solution (1×100 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. stirringThe resulting solid was stirred in acetonitrile (25 mL) for 20 min
  8. waitplaced in the freezer for 1 h
  9. filtrationThe solids were collected by filtration
  10. washwashed with cold acetonitrile
  11. customdried in vacuo

Sources & evidence

ORD record
ord-1dc0fd9b27bf438687a4cbc4e28d7ab1
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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