2-Chloro-5-methylpyrimidin-4-amine → 4-[4-(4-Amino-5-methyl-pyrimidin-2-ylamino)-benzyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1170737Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 2-chloro-5-methyl-pyrimidin-4-ylamine (0.35 g, 2.4 mmol) and 4-(4-amino-benzyl)-piperazine-1-carboxylic acid tert-butyl ester (0.80 g, 2.8 mmol) in acetic acid (20 mL) was heated at 70° C. for 1 d. After cooling to room temperature, the mixture was concentrated. The residue was taken in water (30 mL) and neutralized with 10% NaOH solution until pH˜10. The resulting aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic layers washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the title compound used in the next step without purification. MS (ES+): m/z 399 (M+H)+.

Workup

temperatureAfter cooling to room temperature
concentrationthe mixture was concentrated
extractionThe resulting aqueous layer was extracted with EtOAc (2×30 mL)
washthe combined organic layers washed with brine
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated
customthe title compound used in the next step without purification

Sources & evidence

ORD record: ord-736defdc00174623ba5a4e01d84a87bd
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07825246B2

Reaction notes

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