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

HRID 1963926Notes

Reaction equation

HRID 1963926 reaction equation
ClC1C(C2C(Cl)=CN=C(N[C@H]3CC[C@H](N[CH2:31][C@H:32]([OH:37])[C:33]([F:36])([F:35])[F:34])CC3)C=2)=NC(NCC2CCOCC2)=CC=1.[NH2:38][C@H:39]1[CH2:44][CH2:43][C@H:42]([NH:45][C:46]2[CH:51]=[C:50]([C:52]3[C:57]([Cl:58])=[CH:56][CH:55]=[C:54]([NH:59][CH2:60][CH:61]4[CH2:66][CH2:65][O:64][C:63]([CH3:68])([CH3:67])[CH2:62]4)[N:53]=3)[C:49]([Cl:69])=[CH:48][N:47]=2)[CH2:41][CH2:40]1.FC(F)(F)[C@H]1OC1>CC(O)C>[Cl:58][C:57]1[C:52]([C:50]2[C:49]([Cl:69])=[CH:48][N:47]=[C:46]([NH:45][C@H:42]3[CH2:43][CH2:44][C@H:39]([NH:38][CH2:31][C@H:32]([OH:37])[C:33]([F:36])([F:35])[F:34])[CH2:40][CH2:41]3)[CH:51]=2)=[N:53][C:54]([NH:59][CH2:60][CH:61]2[CH2:66][CH2:65][O:64][C:63]([CH3:67])([CH3:68])[CH2:62]2)=[CH:55][CH:56]=1

Participants

5

Reactant 3

HCID 7171781(2S)-2-(Trifluoromethyl)oxiraneHCID 178425490HCID 178425490, compoundHCID 178521650HCID 178521650, compound

Product 1

HCID 178425491HCID 178425491, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

Preparation of (S)-3-(trans-4-(3,5′-dichloro-6-((tetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)-1,1,1-trifluoropropan-2-ol: 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, 12 H) 1.33-1.66 (m, 4 H) 1.82-1.99 (m, 1 H) 1.99-2.21 (m, 4 H) 2.89-3.04 (m, 2 H) 3.04-3.19 (m, 2 H) 3.27 (d, J=2.35 Hz, 2 H) 4.40 (br. s., 1 H) 6.38 (s, 1 H) 6.55 (d, J=9.00 Hz, 1 H) 6.77 (br. s., 1 H) 6.91 (br. s., 1 H) 7.21 (br. s., 1 H) 7.48 (d, J=9.00 Hz, 1 H) 8.03 (s, 1H)

Workup

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

Sources & evidence

ORD record
ord-e17aaa2a566946da8a92bf3bdf1bfbb9
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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