Diisopropylethylamine → Methyl 2-(4-ethyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylate

HRID 1911470Notes

Reaction equation

HRID 1911470 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][N:3]=1.[CH2:12]([N:14]1[CH2:20][CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)[CH3:13].C(N(C(C)C)C(C)C)C>ClCCl>[CH2:12]([N:14]1[CH2:20][CH2:19][CH2:18][N:17]([C:2]2[N:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][N:3]=2)[CH2:16][CH2:15]1)[CH3:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 75775381-Ethyl-1,4-diazepaneHCID 12627752Methyl 2-chloropyrimidine-5-carboxylate

Product 1

HCID 66589959Methyl 2-(4-ethyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylateYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of methyl 2-chloropyrimidine-5-carboxylate (200 mg, 1.16 mmol) in dichloromethane (4.00 mL) was added to a stirred solution of 1-ethyl-1,4-diazepane (149 mg, 1.16 mmol) and N-ethyl-N-propan-2-ylpropan-2-amine (0.902 mL, 5.22 mmol) in dichloromethane (4.00 mL) at 25° C. The resulting solution was stirred at ambient temperature for 18 h. The reaction mixture was evaporated to dryness and redissolved in MeOH (20 mL) and the crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford methyl 2-(4-ethyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylate (268 mg, 87%) as a cream oil which crystallised on standing. This was used directly with no further purification.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionredissolved in MeOH (20 mL)
  3. customthe crude product was purified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-e5aa80c8ed514a9abcd444ceab0e3857
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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