Diisopropylethylamine → 2-{[2-(3-Chlorophenylamino)pyrimidin-4-ylamino]methyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1803920Notes

Reaction equation

HRID 1803920 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)[N:3]=1.[NH2:16][CH2:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][N:19]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].C(N(C(C)C)CC)(C)C>C1COCC1>[C:27]([O:26][C:24]([N:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH:18]1[CH2:17][NH:16][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)[N:3]=1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2756482tert-Butyl 2-(aminomethyl)piperidine-1-carboxylateHCID 590282434-chloro-N-(3-chlorophenyl)pyrimidin-2-amine

Product 1

HCID 578613172-{[2-(3-Chlorophenylamino)pyrimidin-4-ylamino]methyl}-piperidine-1-carboxylic acid tert-butyl esterYield 51.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-chloro-N-(3-chlorophenyl)pyrimidin-2-amine (300 mg, 1.25 mmol) and tert-butyl 2-(aminomethyl)-piperidine-1-carboxylate (540 mg, 2.50 mmol) in THF (10 mL) is added diisopropylethyl-amine (0.43 mL, 2.50 mmol). The reaction is heated at reflux for 18 hours and then cooled to room temperature. The crude reaction is partitioned between EtOAc and sat. NaHCO3. The organic layer is dried (MgSO4), concentrated in vacuo, and purified over silica (MeOH/CH2Cl2) to afford 268 mg (51% yield) of the desired compound: MS (ESI, pos. ion) m/z: 418 (M+1).

Workup

  1. temperatureThe reaction is heated
  2. temperatureat reflux for 18 hours
  3. customThe crude reaction
  4. customis partitioned between EtOAc and sat. NaHCO3
  5. dry with materialThe organic layer is dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. custompurified over silica (MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-23b9f34596f546fa878ed0157cdf3bfc
Source dataset
uspto-grants-2013_01
Patent number
US08354407B2

Reaction notes

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