N-(4-aminocyclohexyl)methanesulfonamide → N-(4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridine-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanesulfonamide

HRID 1046532

Reaction equation

HRID 1046532 reaction equation
CS([C:4]1[N:9]=[C:8]([C:10]2[N:14]3[CH:15]=[CH:16][CH:17]=[C:18]([C:19]([OH:22])([CH3:21])[CH3:20])[C:13]3=[N:12][CH:11]=2)[CH:7]=[CH:6][N:5]=1)=O.[NH2:23][CH:24]1[CH2:29][CH2:28][CH:27]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[CH2:26][CH2:25]1>CN1C(=O)CCC1.O>[OH:22][C:19]([C:18]1[C:13]2[N:14]([C:10]([C:8]3[CH:7]=[CH:6][N:5]=[C:4]([NH:23][CH:24]4[CH2:29][CH2:28][CH:27]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[CH2:26][CH2:25]4)[N:9]=3)=[CH:11][N:12]=2)[CH:15]=[CH:16][CH:17]=1)([CH3:20])[CH3:21]

Participants

5

Reactant 2

HCID 18348422N-(4-aminocyclohexyl)methanesulfonamideHCID 666162852-[3-(2-Methylsulfinyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridin-8-yl]-propan-2-ol

Product 1

HCID 46896571N-(4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridine-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanesulfonamideYield 40.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 2-[3-(2-methanesulfinyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-8-yl]-propan-2-ol (0.15 g) and N-(4-amino-cyclohexyl)-methanesulfonamide (0.325 g) in NMP (1.5 mL) was treated with TEA (0.33 mL) and heated at 105° C. for 18 h. The reaction mixture was then cooled to RT and diluted with water. The resulting precipitate was filtered, washed with water, and dried. The product was purified by ISCO using 100% DCM to 15% MeOH/DCM. Pure fractions were collected, concentrated, and titurated with EtOAc. The resulting solid was filtered and dried at 50° C. under vacuum overnight to provide N-(4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridine-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanesulfonamide (compound 3, 84.9 mg).

Workup

  1. temperatureThe reaction mixture was then cooled to RT
  2. filtrationThe resulting precipitate was filtered
  3. washwashed with water
  4. customdried
  5. customThe product was purified by ISCO
  6. customPure fractions were collected
  7. concentrationconcentrated
  8. filtrationThe resulting solid was filtered
  9. customdried at 50° C. under vacuum overnight

Sources & evidence

ORD record
ord-ff4c82885dc34545a3e02abac5381f64
Source dataset
uspto-grants-2013_10
Patent number
US08569306B2

Linked notes

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