(2S)-2-(Trifluoromethyl)oxirane → HCID 178425491, compound

HRID 1623358Notes

Reaction equation

[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:14]=[C:13]([C:15]3[C:20]([Cl:21])=[CH:19][CH:18]=[C:17]([NH:22][CH2:23][CH:24]4[CH2:29][CH2:28][O:27][C:26]([CH3:31])([CH3:30])[CH2:25]4)[N:16]=3)[C:12]([Cl:32])=[CH:11][N:10]=2)[CH2:4][CH2:3]1.[F:33][C:34]([F:39])([F:38])[C@H:35]1[O:37][CH2:36]1>CC(O)C>[Cl:21][C:20]1[C:15]([C:13]2[C:12]([Cl:32])=[CH:11][N:10]=[C:9]([NH:8][C@H:5]3[CH2:6][CH2:7][C@H:2]([NH:1][CH2:36][C@H:35]([OH:37])[C:34]([F:39])([F:38])[F:33])[CH2:3][CH2:4]3)[CH:14]=2)=[N:16][C:17]([NH:22][CH2:23][CH:24]2[CH2:29][CH2:28][O:27][C:26]([CH3:30])([CH3:31])[CH2:25]2)=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of N2′-(trans-4-aminocyclohexyl)-3,5′-dichloro-N6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine (19 mg, 0.040 mmol) in 2-propanol (0.3 mL) was added (S)-(−)-3,3,3-trifluoro-1,2-epoxypropane (3.4 uL, 0.040 mmol). The mixture was stirred at 70° C. for 2 hr. The reaction mixture was concentrated. The resulting residue was purified by reverse phase HPLC and lyophilized to give 9.1 mg of (2S)-3-(trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)-1,1,1-trifluoropropan-2-ol as its TFA salt. LCMS (m/z): 590.5 (MH+), retention time=0.71 min; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.81-1.32 (m, 12H) 1.33-1.66 (m, 4H) 1.82-1.99 (m, 1H) 1.99-2.21 (m, 4H) 2.89-3.04 (m, 2H) 3.04-3.19 (m, 2H) 3.27 (d, J=2.35 Hz, 2H) 4.40 (br. s., 1H) 6.38 (s, 1H) 6.55 (d, J=9.00 Hz, 1H) 6.77 (br. s., 1H) 6.91 (br. s., 1H) 7.21 (br. s., 1H) 7.48 (d, J=9.00 Hz, 1H) 8.03 (s, 1H)

Workup

concentrationThe reaction mixture was concentrated
customThe resulting residue was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-f3c29b7c517d4b3c8238794b451c55e1
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778951B2

Reaction notes

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