Diisopropylethylamine → HCID 86714789, compound

HRID 2171938Notes

Reaction equation

HRID 2171938 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[CH2:10]([O:12][C:13](=[O:24])[CH2:14][CH:15]([NH2:23])[C:16]1([CH3:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH3:11].C(N(CC)C(C)C)(C)C>C1COCC1.CO>[Cl:1][C:2]1[N:7]=[C:6]([NH:23][CH:15]([C:16]2([CH3:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][C:13]([O:12][CH2:10][CH3:11])=[O:24])[C:5]([F:9])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 71247350HCID 71247350, compound2×

Product 1

HCID 86714789HCID 86714789, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 2,4-dichloro-5-fluoro-pyrimidine (1.83 g, 85.33 mmol), racemic ethyl-3-amino-3-(1-methylcyclohexyl)propanoate, 205a, (2.34 g, 11.0 mmol) and N,N-diisopropylethylamine (4.79 g, 27.50 mmol) in THF (40 mL) and methanol (10 mL) was heated at 95° C. for 3 hours. The solution was cooled to room temperature and the solvent was evaporated under reduced pressure. The crude residue was purified by silica gel chromatography (0-60% EtOAc/Hexanes gradient) to afford 620 mg of the desired product as a white foamy solid: 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J=2.6 Hz, 1H), 5.37 (m, 1H), 4.59 (m, 1H), 4.00 (q, 7.2 Hz, 2H), 2.62 (dd, J=14.7, 3.8 Hz, 1H), 1.67 (m, 1H), 1.17 (m, 10H), 1.10 (t, J=7.1 Hz, 3H), 0.85 (s, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.69 minutes (M+H) 344.39.

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customthe solvent was evaporated under reduced pressure
  3. customThe crude residue was purified by silica gel chromatography (0-60% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-91ea8613c1ae4aad96176dedb1b6d633
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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