Diisopropylethylamine → HCID 59751987, compound

HRID 749108Notes

Reaction equation

HRID 749108 reaction equation
Cl.[NH2:2][C@@H:3]([CH3:8])[C:4]([CH3:7])([OH:6])[CH3:5].CCN(C(C)C)C(C)C.Cl[C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH:22]=[CH:21][N:20]=1>CN1CCCC1=O.O>[CH3:33][O:32][C:29]1[CH:28]=[CH:27][C:26]([NH:25][C:23]2[CH:22]=[CH:21][N:20]=[C:19]([NH:2][C@@H:3]([CH3:8])[C:4]([CH3:7])([OH:6])[CH3:5])[N:24]=2)=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 219952032-Chloro-N-(4-methoxyphenyl)pyrimidin-4-amineHCID 73424833(S)-3-amino-2-methylbutan-2-ol

Product 1

HCID 59751987HCID 59751987, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

(3S)-3-Amino-2-methyl-butan-2-ol HCl (1.00 mg, 7.16 mmol; prepared using the method of Konno et. al., Chem. Pharm. Bull. 1997, 45, 185) is dissolved in N-methyl-pyrrolidinone (10 mL). Hunig's base (1.62 mL, 9.30 mmol) is added followed by (2-chloropyrimidin-4-yl)-(4-methoxyphenyl)-amine, 1, (789 mg, 3.35 mmol) and the solution warmed to 140° C. After 24 hours, the reaction mixture is cooled to room temperature and diluted with water (100 mL) and the mixture extracted three times with CH2Cl2 (100 mL). The combined organic layers are washed with saturated aqueous sodium bicarbonate solution (100 mL) and brine (100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product is purified over silica (100% CH2Cl2 to 5% to 10% MeOH/CH2Cl2) to afford 564 mg (46% yield) of the desired product as a tan solid. 1H NMR (300 MHz, CDCl3) δ 7.78 (d, J=5.8 Hz, 1H), 7.20 (d, J=9.0 Hz, 2H), 6.87 (d, J=9.0 Hz, 2H), 5.87 (d, J=5.8 Hz, 1H), 4.00-3.90 (m, 1H), 3.80 (s, 3H), 2.83 (s, 3H), 1.25 (s, 3H), 1.18 (d, J=7.3 Hz, 3H), 1.17 (s, 3H); MS (ESI) m/z 303 (M+1).

Workup

  1. customprepared
  2. temperaturethe reaction mixture is cooled to room temperature
  3. extractionthe mixture extracted three times with CH2Cl2 (100 mL)
  4. washThe combined organic layers are washed with saturated aqueous sodium bicarbonate solution (100 mL) and brine (100 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified over silica (100% CH2Cl2 to 5% to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ecc706f73226465d882b32d16f6683ca
Source dataset
uspto-grants-2008_07
Patent number
US07402589B2

Reaction notes

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