Water → 4-{4-[4-(3-Methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid methyl ester

HRID 237429Notes

Reaction equation

HRID 237429 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[C:12]([O:17][CH2:18][CH2:19][CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:13]=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)[CH:5]=[CH:4][N:3]=1.Cl.[CH2:26]([O:28][C:29]([CH:31]1[CH2:36][CH2:35][CH:34]([NH2:37])[CH2:33][CH2:32]1)=[O:30])C.C([O-])([O-])=O.[K+].[K+].O>CN1C(=O)CCC1>[CH3:26][O:28][C:29]([CH:31]1[CH2:36][CH2:35][CH:34]([NH:37][C:2]2[N:7]=[C:6]([N:8]3[C:16]4[C:11](=[C:12]([O:17][CH2:18][CH2:19][CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:13]=[CH:14][CH:15]=4)[CH:10]=[CH:9]3)[CH:5]=[CH:4][N:3]=2)[CH2:33][CH2:32]1)=[O:30]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 11586508trans-Ethyl 4-aminocyclohexanecarboxylate hydrochlorideHCID 580170801-(2-chloro-pyrimidin-4-yl)-4-(3-methanesulfonyl-propoxy)-1H-indole

Product 1

HCID 580170934-{4-[4-(3-Methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid methyl esterYield 97%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-(2-Chloro-pyrimidin-4-yl)-4-(3-methanesulfonyl-propoxy)-1H-indole (300 g), 4-amino-cyclohexanecarboxylic acid ethyl ester HCl salt (155 g), and K2CO3(170 g) in NMP (2.35 L) were stirred at 80° C. for 5 h and then stirred overnight at room temperature. The reaction mixture was then stirred on an ice bath, and 2.5 L water was slowly added while stirring, and cooling continued until completion of the exothermic reaction. Upon cooling, the mixture was filtered, and resulting solid was rinsed with H2O and dried in vacuo overnight to yield 4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid methyl ester (97%).

Workup

  1. stirringThe reaction mixture was then stirred on an ice bath
  2. stirringwhile stirring
  3. temperaturecooling
  4. customcontinued until completion of the exothermic reaction
  5. temperatureUpon cooling
  6. filtrationthe mixture was filtered
  7. customresulting solid
  8. washwas rinsed with H2O
  9. customdried in vacuo overnight

Sources & evidence

ORD record
ord-71369965bd674f87bb96abca0888c387
Source dataset
uspto-grants-2014_02
Patent number
US08642601B2

Reaction notes

Loading…