Hydrochloric Acid → N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(1-aminoethyl)-6-methylpyrimidinamine

HRID 1251507Notes

Reaction equation

HRID 1251507 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:22][CH3:23])[C:12]1[N:17]=[C:16]([C:18](=[O:20])[CH3:19])[CH:15]=[C:14]([CH3:21])[N:13]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:30].[Na+].Cl>CO.C(Cl)(Cl)Cl.C(OCC)(=O)C>[NH4+:11].[OH-:20].[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:22][CH3:23])[C:12]1[N:17]=[C:16]([CH:18]([NH2:30])[CH3:19])[CH:15]=[C:14]([CH3:21])[N:13]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 18323676N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamine

Product 2

HCID 14923Ammonium HydroxideHCID 18323742N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(1-aminoethyl)-6-methylpyrimidinamineYield 71.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methyl-pyrimidinamine (0.5 g, 1.33 mmol), ammonium acetate (1.1 g, 14 mmol), sodium cyanoborohydride (59 mg, 0.9 mmol) and methanol (5 mL) was stirred at ambient temperature for 90 h. A concentrated HCl solution was added until the solution became acidic (pH=2), then the reaction mixture was concentrated in vacuo. The residue was taken up in water, basified with a concentrated NaOH solution and extracted three times with ether. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an oil. Column chromatography (ethyl acetate:hexanes:: 1: then chloroform:methanol:NH4OH::95:5:0.5) gave (1) N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(1-aminothyl)-6-methyl-pyrimidinamine (80 mg, 16% yield, Rf 0.34 (ethyl acetate:hexanes::1;1)) and (2) the title product as a brown oil (180 mg, 36% yield, Rf 0.34 (chloroform:methanol:NH4OH::95:5:0.5)): NMR (CDCl3, 300 MHz): 7.5 (d, 1H, J=1), 7.2-7.1 (m, 2H), 6.4 (s, 1H), 4.25-4.05 (m, 1H), 3.9-3.65 (m, 2H), 3.0-2.85 (m, 1H), 2.4-2.2 (br m, 3H), 1.9-1.6 (br m, 3H), 1.3 (d, 6H, J=8), 1.2 (t, 3H, J=8); CI-HRMS (C18H25BrN4): 377.1341 (M+H), Found: 377.1330.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. extractionextracted three times with ether
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give an oil

Sources & evidence

ORD record
ord-882dd9b79714471bb16885b707bce024
Source dataset
uspto-grants-2002_01
Patent number
US06342503B1

Reaction notes

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