2,4-Dichloro-5-fluoropyrimidine → N1-(2-chloro-5-fluoropyrimidin-4-yl)-5-methylcyclohexane-1,3-diamine

HRID 527097Notes

Reaction equation

HRID 527097 reaction equation
[CH3:1][CH:2]1[CH2:7][CH:6]([NH2:8])[CH2:5][CH:4]([NH2:9])[CH2:3]1.[Cl:10][C:11]1[N:16]=[C:15](Cl)[C:14]([F:18])=[CH:13][N:12]=1>C(O)(C)C.C(#N)C>[Cl:10][C:11]1[N:16]=[C:15]([NH:8][CH:6]2[CH2:7][CH:2]([CH3:1])[CH2:3][CH:4]([NH2:9])[CH2:5]2)[C:14]([F:18])=[CH:13][N:12]=1

Participants

5

Reactant 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 225907615-Methylcyclohexane-1,3-diamine2×

Product 1

HCID 86667457N1-(2-chloro-5-fluoropyrimidin-4-yl)-5-methylcyclohexane-1,3-diamine

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-methylcyclohexane-1,3-diamine, 76a, (2.2 g, 17.2 mmol) in isopropyl alcohol (40 ml) and acetonitrile (40 ml) was added 2,4-dichloro-5-fluoropyrimidine (1.4 g, 8.6 mmol). The mixture was stirred at room temperature overnight, concentrated to dryness, and purified on silica gel eluted with 1-20% methanol/dichloromethane, to give 0.6 g of racemic N1-(2-chloro-5-fluoropyrimidin-4-yl)-5-methylcyclohexane-1,3-diamine: 1H NMR (300 MHz, MeOD) δ 7.85 (d, J=3.5 Hz, 1H), 4.07 (ddd, J=11.9, 7.9, 4.1 Hz, 1H), 3.54 (qd, J=11.3, 4.2 Hz, 1H), 2.82 (tt, J=11.4, 3.7 Hz, 1H), 2.16 (dd, J=15.0, 13.0 Hz, 1H), 1.89 (t, J=13.4 Hz, 2H), 1.50 (dd, J=76.0, 21.9 Hz, 2H), 1.10 (dt, J=17.9, 9.0 Hz, 1H), 0.99 (dd, J=8.5, 5.0 Hz, 3H), 0.81 (ddd, J=23.8, 12.0, 8.2 Hz, 1H); LCMS RT=1.24 (M+1) 259.1.

Workup

  1. concentrationconcentrated to dryness
  2. custompurified on silica gel
  3. washeluted with 1-20% methanol/dichloromethane

Sources & evidence

ORD record
ord-c45fda78cc284b86a875141e4d12a60f
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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