Diisopropylethylamine → tert-butyl {(3R)-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidin-3-yl}carbamate

HRID 383783Notes

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

To the mixture of 2-chloro-6-methyl-N-(1H-pyrazol-5-yl)pyrimidin-4-amine prepared in Referential Example 1 (25.5 mg) and (R)-3-(tert-butoxycarbonylamino)piperidine (50.9 mg) in DMSO (5 ml) was added DIEA (210.0 μL). And the mixture was heated to 110° C. under stirring for overnight. The resulting mixture was cooled to room temperature, poured into brine and extracted with EtOAc. The extract was washed with saturated aqueous solution of NaHCO3, dried over Na2SO4 and concentrated in vacuo. And the residue was purified with silica gel column chromatography (eluent: hexane/EtOAc=99/1˜0/100) to give tert-butyl {(3R)-1-[4-methyl-6-(1H-pyrazol-5-ylamino)pyrimidin-2-yl]piperidin-3-yl}carbamate (26.0 mg) as a pale yellow solid.

Workup

temperatureThe resulting mixture was cooled to room temperature
extractionextracted with EtOAc
washThe extract was washed with saturated aqueous solution of NaHCO3
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customAnd the residue was purified with silica gel column chromatography (eluent: hexane/EtOAc=99/1˜0/100)

Sources & evidence

ORD record: ord-cddb68a583b2453ca53ceb58595ebbee
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367690B2

Reaction notes

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