Water → [4-Amino-2-[1-(3,5-dimethyl-isoxazole-4-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone

HRID 1435243Notes

Reaction equation

HRID 1435243 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[N:3]=1.C(N(C(C)C)CC)(C)C.[CH3:35][C:36]1[C:40]([S:41](Cl)(=[O:43])=[O:42])=[C:39]([CH3:45])[O:38][N:37]=1.O>O1CCCC1>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:21][CH2:22][N:23]([S:41]([C:40]3[C:36]([CH3:35])=[N:37][O:38][C:39]=3[CH3:45])(=[O:43])=[O:42])[CH2:24][CH2:25]2)[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27363193,5-Dimethylisoxazole-4-sulfonyl chlorideHCID 9997668[4-Amino-2-(piperidin-4-ylamino)-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone

Product 1

HCID 9983599[4-Amino-2-[1-(3,5-dimethyl-isoxazole-4-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of [4-amino-2-(piperidin-4-ylamino)-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone (75 mg, 0.22 mmol, Example 59) and diisopropylethylamine (2 mL) in tetrahydrofuran (40 mL) was stirred at +5° C. To this was added dropwise 3,5-dimethyl-isoxazole-4-sulfonyl chloride (100 mg, 0.51 mmol, Maybridge). The reaction was stirred at room temperature for 2 hours, poured into water and extracted into methylene chloride (2×50 mL). The combined organic extracts were washed with 5% aqueous sodium bicarbonate. The organic solution was dried (Na2SO4) and solvent was removed under vacuum to give a crude solid. Purification was by silica gel chromatography to give [4-amino-2-[1-(3,5-dimethyl-isoxazole-4-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone as a white solid. HRMS, observed: 505.1669; Calcd for M+: 505.1664.

Workup

  1. extractionextracted into methylene chloride (2×50 mL)
  2. washThe combined organic extracts were washed with 5% aqueous sodium bicarbonate
  3. dry with materialThe organic solution was dried (Na2SO4) and solvent
  4. customwas removed under vacuum
  5. customto give a crude solid
  6. customPurification

Sources & evidence

ORD record
ord-c4e78edd004d470da5bde3360852130f
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

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