Potassium Carbonate → HCID 57494063, compound

HRID 1689921Notes

Reaction equation

HRID 1689921 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH3:14])[NH:11][C@H:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:17][C:18]1[S:26][C:25]2[C:24]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[N:23][C:22]([Cl:33])=[N:21][C:20]=2[CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>CC#N.C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([CH2:17][C:18]2[S:26][C:25]3[C:24]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[N:23][C:22]([Cl:33])=[N:21][C:20]=3[CH:19]=2)[C@@H:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 10822535tert-butyl (3R,5S)-3,5-dimethylpiperazine-1-carboxylateHCID 461807264-(6-(Bromomethyl)-2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine

Product 1

HCID 57494063HCID 57494063, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of (3R,5S)-3,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (0.92 g), 6-bromomethyl-2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (1 g) and potassium carbonate (1.59 g) in MeCN (10 ml) was heated to reflux for 5 days. The reaction mixture was subsequently cooled, diluted with chloroform, washed with brine and dried (MgSO4), and the solvent was removed in vacuo. The residue was purified by flash column chromatography to yield (3S,5R)-4-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-3,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester, 170 (1.2 g). Treatment of this compound with HCl in DCM/MeOH produced 2-chloro-6-(2S,6R)-2,6-dimethyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine, 171, which was then methylated using 37% formaldehyde solution and sodium borohydride in MeOH, furnishing 172.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 days
  3. temperatureThe reaction mixture was subsequently cooled
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-cab94f7059a24e508ed1c98bc09d574b
Source dataset
uspto-grants-2012_04
Patent number
US08153629B2

Reaction notes

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