Hydrochloric Acid → 3-(2-chlorophenyl)-7-(4-hydroxymethylcyclohexylamino)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one

HRID 1280583

Reaction equation

HRID 1280583 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13](S(C)(=O)=O)=[N:14][CH:15]=2)[NH:10][C:9]1=[O:22].[NH2:23][CH:24]1[CH2:29][CH2:28][CH:27]([CH2:30][OH:31])[CH2:26][CH2:25]1.CN1CCCC1=O.Cl>O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13]([NH:23][CH:24]3[CH2:29][CH2:28][CH:27]([CH2:30][OH:31])[CH2:26][CH2:25]3)=[N:14][CH:15]=2)[NH:10][C:9]1=[O:22]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 424390((1s,4s)-4-Aminocyclohexyl)methanolHCID 184254033-(2-chloro-phenyl)-7-methylsulfonyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one

Product 1

HCID 184254783-(2-chlorophenyl)-7-(4-hydroxymethylcyclohexylamino)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sulfone 11.1 (350 mg, 104 mmol) was combined with 4-aminocyclohexylmethanol 1:1 cis/trans) (400 mg, 3.3 mmol) (prepared as described in Chem.Ber.; GE; 96; 1963; 2377-2386) with 0.3 mL of 1-methyl-2-pyrrolidinone. The mixture was heated at 1000 for 2 hours at which time it was cooled to room temperature. The reaction mixture was added to water and extracted with ethyl acetate, washed with water, dried, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 10:90 methanol/dichloromethane as eluant The column fractions containing the product were concentrated to a foam which was resuspended in methanol. Addition of hydrochloric acid (1.0M/Et2O, 1.0 equivalent) gave a salt which was filtered to give the hydrochloride salt of 3-(2-chlorophenyl)-7-(4-hydroxymethylcyclohexylamino)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one.

Workup

  1. temperatureThe mixture was heated at 1000 for 2 hours at which time it
  2. extractionextracted with ethyl acetate
  3. washwashed with water
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel using 10:90 methanol/dichloromethane as eluant The column fractions
  7. additioncontaining the product
  8. concentrationwere concentrated to a foam which
  9. customgave a salt which
  10. filtrationwas filtered

Sources & evidence

ORD record
ord-c23dc90ac8724cd18c353be3668f7956
Source dataset
uspto-grants-2002_09
Patent number
US06451804B1

Linked notes

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