Diisopropylethylamine → (1S,3R)-2,2-Dimethyl-3-((2-(methylthio)-5-(trifluoromethyl)pyrimidin-4-yl)amino)cyclobutanol
Reaction equation
Cl.[NH2:2][CH:3]1[CH2:6][CH:5]([OH:7])[C:4]1([CH3:9])[CH3:8].CCN(C(C)C)C(C)C.Cl[C:20]1[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][N:23]=[C:22]([S:30][CH3:31])[N:21]=1>C1COCC1.CN(C=O)C>[CH3:8][C:4]1([CH3:9])[C@H:3]([NH:2][C:24]2[C:25]([C:26]([F:28])([F:29])[F:27])=[CH:20][N:21]=[C:22]([S:30][CH3:31])[N:23]=2)[CH2:6][C@@H:5]1[OH:7]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
In a round-bottomed flask, 3-amino-2,2-dimethylcyclobutanol hydrochloride (peak 1, obtained above) (1.0 equiv.) and DIEA (1.3 equiv.) were combined in THF (1.0 M) and DMF (1.0 M). To this solution was added 4-chloro-2-(methylthio)-5-(trifluoromethyl)pyrimidine (1.0 equiv.) at 0° C. The mixture was allowed to warm to room temperature over 2 h; LCMS showed the desired product. Ethyl acetate was added and the organic phase was separated and dried over sodium sulfate. The organic phase was filtered and concentrated to a residue. The dried residue was purified by silica gel chromatography (Biotage column, 0-50% hexane in ethyl acetate; 340 g SNAP column). Concentration of the desired fractions afforded the title compound. The stereochemistry was determined as described for other intermediates described herein, by X-ray crystallography. 1H NMR (500 MHz, CDCl3) δ (ppm) 8.22 (d, J=0.63 Hz, 1H) 5.21 (br. s., 1H) 4.08-4.23 (m, 1H) 3.78-3.91 (m, 1H) 2.80 (dt, J=11.66, 7.41 Hz, 1H) 2.52-2.57 (m, 3H) 1.79 (ddd, J=11.66, 9.46, 7.88 Hz, 1H) 1.67 (d, J=6.31 Hz, 1H) 1.24-1.32 (m, 3H) 0.97-1.06 (m, 3H).
Sources & evidence
- ORD record
- ord-8e97e027a0c94a698c57e951e00feb62
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09156798B2
Reaction notes
Loading…