Water → (+/-)-2-Chloro-4-(octahydro-5,5-dimethylindolizin-7-ylamino)pyrimidine-5-carboxamide

HRID 1754397Notes

Reaction equation

HRID 1754397 reaction equation
[CH3:1][C:2]1([CH3:12])[CH2:10][CH:9]([NH2:11])[CH2:8][CH:7]2[N:3]1[CH2:4][CH2:5][CH2:6]2.[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([C:21]([NH2:23])=[O:22])=[CH:16][N:15]=1.O>CO>[Cl:13][C:14]1[N:19]=[C:18]([NH:11][CH:9]2[CH2:8][CH:7]3[N:3]([CH2:4][CH2:5][CH2:6]3)[C:2]([CH3:12])([CH3:1])[CH2:10]2)[C:17]([C:21]([NH2:23])=[O:22])=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 962WaterHCID 212230802,4-Dichloropyrimidine-5-carboxamideHCID 867044455,5-Dimethyloctahydroindolizin-7-amine

Product 1

HCID 86704453(+/-)-2-Chloro-4-(octahydro-5,5-dimethylindolizin-7-ylamino)pyrimidine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A mixture of (±)-octahydro-5,5-dimethylindolizin-7-amine (0.65 g, 3.9 mmol) in MeOH (10 ml) was added to a stirred solution of 2,4-dichloropyrimidine-5-carboxamide (0.75 g, 3.9 mmol; prepared according to the procedure set forth in US patent application publication US20110130415, page 41) in MeOH (30 ml) and H2O (4 ml) at 0° C. under nitrogen. After complete addition, the mixture was slowly warmed to room temperature and stirred at room temperature overnight. The mixture was then concentrated in vacuo and the residue partitioned between EtOAc (150 ml) and 1N NaOH (100 ml). The aqueous layer was extracted with EtOAc (1×100 ml) and the combined organic extracts were dried (Na2SO4), filtered and the solvent removed in vacuo. The residue was dry-loaded on to basic alumina (Brockmann grade IV) and then purified by column chromatography on basic alumina (Brockmann grade IV) using CH2Cl2/MeOH (1:0 to 95:5) as eluent to give the product (550 mg).

Workup

  1. customprepared
  2. customat 0° C.
  3. additionAfter complete addition
  4. concentrationThe mixture was then concentrated in vacuo
  5. customthe residue partitioned between EtOAc (150 ml) and 1N NaOH (100 ml)
  6. extractionThe aqueous layer was extracted with EtOAc (1×100 ml)
  7. dry with materialthe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. custompurified by column chromatography on basic alumina (Brockmann grade IV)

Sources & evidence

ORD record
ord-13e5a13bd5984e4f819ea1bd9d8181cd
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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