Ammonia → HCID 21070479, compound

HRID 1435320Notes

Reaction equation

HRID 1435320 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][N:23]([S:26]([CH2:29][CH2:30][CH2:31]Cl)(=[O:28])=[O:27])[CH2:22][CH2:21]2)[N:3]=1.[I-].[K+].[NH3:35].C(N(C(C)C)CC)(C)C.[CH3:45][S:46](Cl)(=[O:48])=[O:47]>>[NH2:1][C:2]1[C:7]([C:8](=[O:9])[C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:25][CH2:24][N:23]([S:26]([CH2:29][CH2:30][CH2:31][NH:35][S:46]([CH3:45])(=[O:48])=[O:47])(=[O:28])=[O:27])[CH2:22][CH2:21]2)[N:3]=1

Participants

6

Reactant 5

HCID 222AmmoniaHCID 4875Potassium IodideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 10458099[4-Amino-2-[1-(3-chloro-propane-1-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone

Product 1

HCID 21070479HCID 21070479, compoundYield 26%

Conditions

Temperature
105 °C

Procedure

A suspension of [4-amino-2-[l -(3-chloro-propane-1-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone (210 mg, 0.43 mmol, Example 272), potassium iodide (200 mg, 1.2 mmol) and ammonia (1.5 mL, 7M in methanol, Aldrich) was heated at 100-110° C. in a sealed tube with stirring for 6 hours. Solvent was removed and the crude amine product was dissolved in tetrahydrofuran (12 mL). The resulting solution was cooled to 0-5° C., treated with diisopropylethylamine (200 mg, 2.0 mmol, Aldrich) and then with a bolus of methanesulfonyl chloride (100 mg, 0.88 mmol, Aldrich). After stirring at ambient temperature for 3 hours, the solution was washed with 10% NaHCO3. The organic layer was separated and dried (Na2SO4). The residue was purified by silica gel chromatography (5% methanol/methylene chloride) and precipitated from tetrahydrofuran/ethyl ether to give N-(3-[4-[4-amino-5-(5-fluoro-2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-sulfonyl]-propyl)-methanesulfonamide as a white solid (60 mg, 26% yield). HRMS, observed: 445.1652; Calcd for (M+H)+: 445.1647

Workup

  1. customSolvent was removed
  2. dissolutionthe crude amine product was dissolved in tetrahydrofuran (12 mL)
  3. temperatureThe resulting solution was cooled to 0-5° C.
  4. stirringAfter stirring at ambient temperature for 3 hours
  5. washthe solution was washed with 10% NaHCO3
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. customThe residue was purified by silica gel chromatography (5% methanol/methylene chloride)
  9. customprecipitated from tetrahydrofuran/ethyl ether

Sources & evidence

ORD record
ord-0ddacfaa33114b6aa726f5f29e928b06
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

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