Diisopropylethylamine → HCID 178433071, compound

HRID 472226Notes

Reaction equation

HRID 472226 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])=[N:6][C:7]=1[CH3:8].Cl.[NH2:18][C@H:19]1[CH2:24][CH2:23][C@H:22]([OH:25])[CH2:21][CH2:20]1.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O.COC(C)(C)C>[Br:1][C:2]1[C:3]([NH:18][C@H:19]2[CH2:24][CH2:23][C@H:22]([OH:25])[CH2:21][CH2:20]2)=[N:4][C:5]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])=[N:6][C:7]=1[CH3:8]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 592588485-bromo-4-chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidineHCID 178479278HCID 178479278, compound

Product 1

HCID 178433071HCID 178433071, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 15413tert-Butyl methyl etherSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 5-bromo-4-chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidine (1.50 g, 4.99 mmol), trans-4-aminocyclohexanol hydrochloride (1.17 g, 6.24 mmol), and diisopropylethyl amine (2.61 mL, 15.0 mmol) in dimethylacetamide (25.0 mL) was heated at 160° C. in a sealed tube overnight. The reaction mixture was diluted with methyltertbutyl ether (400 mL), washed with saturated ammonia chloride (2×) and brine, dried (MgSO4), filtered, and concentrated. The combined aqueous layers were extracted with dichloromethane (3×150 mL), dried (MgSO4), filtered, and concentrated. The crude product was purified by flash chromatography eluting with chloroform/methanol (0.5-3%) to afford trans-4-(5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidin-4-ylamino)cyclohexanol (1.76 g, 93%).

Workup

  1. washwashed with saturated ammonia chloride (2×) and brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. extractionThe combined aqueous layers were extracted with dichloromethane (3×150 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. washeluting with chloroform/methanol (0.5-3%)

Sources & evidence

ORD record
ord-5f71001f8b5d48689f481100bcb64a2a
Source dataset
uspto-grants-2014_01
Patent number
US08633204B2

Reaction notes

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