Diisopropylethylamine → {4-[(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester

HRID 1819424Notes

Reaction equation

[F:1][C:2]1[C:3](Cl)=C[C:5]([Cl:8])=[N:6][CH:7]=1.[NH2:10][CH2:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14][CH2:13]1.CC[N:28](C(C)C)C(C)C>CCO>[C:21]([O:20][C:19](=[O:25])[NH:18][CH:15]1[CH2:14][CH2:13][CH:12]([CH2:11][NH:10][C:3]2[C:2]([F:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:28]=2)[CH2:17][CH2:16]1)([CH3:22])([CH3:24])[CH3:23]

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of the above 5-fluoro-2,4-dichloropyridine (67 mg, 0.4 mol) in EtOH (2 mL) were added tert-butyl trans-4-aminomethylcyclohexylcarbamate (100 mg, 0.44 mmol) and DIPEA (77 μL, 0.44 mmol). The reaction mixture was heated at 40° C. for 1 h. The mixture was concentrated in vacuo and the resulting residue was dissolved in EtOAc and washed with brine. The aqueous layer was re-extracted with EtOAc (×2). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo to yield 127 mg (89%) of {4-[(2-chloro-5-fluoro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester.

Workup

concentrationThe mixture was concentrated in vacuo
dissolutionthe resulting residue was dissolved in EtOAc
washwashed with brine
extractionThe aqueous layer was re-extracted with EtOAc (×2)
dry with materialThe combined organic phase was dried over anhydrous Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-71318567aafe492ba646b1cccd76b9c8
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07601714B2

Reaction notes

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