Morpholine → 2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-N-(1-(propylsulfonyl)azetidin-3-yl)pyrimidin-4-amine

HRID 74881

Reaction equation

HRID 74881 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([NH:6][C:7]2[C:12]([F:13])=[CH:11][N:10]=[C:9]([C:14]3[C:22]4[C:17](=[N:18][CH:19]=[C:20]([Cl:23])[CH:21]=4)[N:16]([S:24]([C:27]4[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[CH:15]=3)[N:8]=2)[CH2:3]1.CCN(C(C)C)C(C)C.[CH2:43]([S:46](Cl)(=[O:48])=[O:47])[CH2:44][CH3:45].N1CCOCC1>C1COCC1>[Cl:23][C:20]1[CH:21]=[C:22]2[C:14]([C:9]3[N:8]=[C:7]([NH:6][CH:4]4[CH2:3][N:2]([S:46]([CH2:43][CH2:44][CH3:45])(=[O:48])=[O:47])[CH2:5]4)[C:12]([F:13])=[CH:11][N:10]=3)=[CH:15][N:16]([S:24]([C:27]3[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:17]2=[N:18][CH:19]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 662791-Propanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67284924N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride2×

Product 1

HCID 672852632-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-N-(1-(propylsulfonyl)azetidin-3-yl)pyrimidin-4-amineYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred suspension of N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride, 6c, (0.055 g, 0.110 mmol) in THF (1 mL) was added iPr2NEt (0.300 mL, 1.720 mmol) followed by propane-1-sulfonyl chloride (0.012 mL, 0.108 mmol). The resulting homogenous light yellow solution mixture was heated at 50° C. for one hour at which time LCMS showed complete reaction. Morpholine (0.20 mL) was added and the solution evaporated to dryness. The resulting residue was dissolved in methanol (2 mL) then treated with 25% sodium methoxide/methanol (0.5 mL) and heated at 60° C. in sealed tube for 10 minutes. The resulting solution was quenched with aqueous saturated NH4Cl solution (0.5 mL) then evaporated to dryness. The resulting residue was dissolved in DMSO and purified by reverse phase HPLC (ammonium formate buffer) to afford 19.8 mg (43% yield) of the desired product, 423, as a solid.

Workup

  1. customreaction
  2. customthe solution evaporated to dryness
  3. dissolutionThe resulting residue was dissolved in methanol (2 mL)
  4. additionthen treated with 25% sodium methoxide/methanol (0.5 mL)
  5. temperatureheated at 60° C. in sealed tube for 10 minutes
  6. customThe resulting solution was quenched with aqueous saturated NH4Cl solution (0.5 mL)
  7. customthen evaporated to dryness
  8. dissolutionThe resulting residue was dissolved in DMSO
  9. custompurified by reverse phase HPLC (ammonium formate buffer)

Sources & evidence

ORD record
ord-4345c0018ae44ee0b8979a71e67f49e1
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Linked notes

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