Water → HCID 117678278, compound

HRID 1778173Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([C:15]([F:18])([F:17])[F:16])[C:11]([NH2:14])=[N:12][CH:13]=2)[CH:5]=[C:4](Cl)[N:3]=1.Cl.[C@H:21]12[CH2:27][C@H:24]([NH:25][CH2:26]1)[CH2:23][N:22]2[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C(N(C(C)C)C(C)C)C.O>O1CCCC1>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([C:6]2[N:7]=[C:2]([Cl:1])[N:3]=[C:4]([N:25]3[CH2:26][C@@H:21]4[CH2:27][C@H:24]3[CH2:23][N:22]4[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:5]=2)=[CH:9][C:10]=1[C:15]([F:18])([F:17])[F:16]

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of 5-(2,6-dichloropyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amine (300 mg, 0.84 mmol) in tetrahydrofuran (60 mL) was added (1S,4S)-tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate hydrochloride (197 mg, 0.84 mmol) and N-ethyl-N-isopropylpropan-2-amine (2 mL). The mixture was heated at 75° C. for 3 h. After cooling to room temperature, water (50 mL) was added to. The mixture was extracted with ethyl acetate (3×30 mL). The organic layer was dried over sodium sulfate, concentrated and purified by flash column chromatography (25% ethyl acetate in petroleum ether to 100% ethyl acetate) to provide (1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-chloropyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (220 mg, 48.1% yield). TLC (Thin layer chromatography) (petroleum ether (PE): ethyl acetate (EA)=3:1, Rf=0.3-0.4).

Workup

temperatureAfter cooling to room temperature
extractionThe mixture was extracted with ethyl acetate (3×30 mL)
dry with materialThe organic layer was dried over sodium sulfate
concentrationconcentrated
custompurified by flash column chromatography (25% ethyl acetate in petroleum ether to 100% ethyl acetate)

Sources & evidence

ORD record: ord-3d5d76d23afd4ea2b964c34b67803f89
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266862B2

Reaction notes

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