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

HRID 1911481Notes

Reaction equation

HRID 1911481 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.[CH:12]1([N:15]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH2:14][CH2:13]1.C(N(C(C)C)C(C)C)C>ClCCl>[CH:12]1([N:15]2[CH2:21][CH2:20][CH2:19][N:18]([C:2]3[N:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][N:3]=3)[CH2:17][CH2:16]2)[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12627752Methyl 2-chloropyrimidine-5-carboxylateHCID 203484761-Cyclopropylhexahydro-1H-1,4-diazepine

Product 1

HCID 66589974Methyl 2-(4-cyclopropyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylateYield 97.3%

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-cyclopropyl-1,4-diazepane (247 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-cyclopropyl-1,4-diazepan-1-yl)pyrimidine-5-carboxylate (312 mg, 97%) as a cream solid. 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-cfd07455b8444d99aa64bd50d860f79c
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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