Potassium tert-butoxide → HCID 118092576, compound

HRID 2207403Notes

Reaction equation

HRID 2207403 reaction equation
CC(C)([O-])C.[K+].Cl[CH2:8][CH2:9][NH:10][C:11]([NH:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[C:25]([NH:27][C:28]3[N:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=3)[CH:24]=[C:23]([CH3:38])[CH:22]=2)=[CH:17][N:16]=1)=[O:12]>C1COCC1>[CH3:38][C:23]1[CH:22]=[C:21]([C:18]2[CH:19]=[CH:20][C:15]([CH2:14][N:13]3[CH2:8][CH2:9][NH:10][C:11]3=[O:12])=[N:16][CH:17]=2)[CH:26]=[C:25]([NH:27][C:28]2[N:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][N:29]=2)[CH:24]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxide2×HCID 118092579HCID 118092579, compound

Product 1

HCID 118092576HCID 118092576, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Potassium tert-butoxide (34.3 mg, 0.305 mmol) was added to a solution of 1-(2-chloroethyl)-3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}urea (129 mg, 0.277 mmol) in THF (4.62 mL). The reaction mixture was stirred at room temperature overnight under an argon atmosphere. An additional equivalent of potassium tert-butoxide was added to the reaction. The solvent was removed under reduced pressure and the residue was directly purified by reverse phase HPLC (10-75% acetonitrile in water+0.5% TFA). The isolated fractions were partitioned between 10% IPA/chloroform and saturated aqueous NaHCO3. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}imidazolidin-2-one. MS APCI calc'd for C21H20F3N6O [M+H]+ 429. found 429. 1H NMR (500 MHz, DMSO-d6) δ 10.27 (s, 1H), 8.82 (d, J=4.8 Hz, 1H), 8.75 (d, J=2.4 Hz, 1H), 8.05-7.83 (m, 2H), 7.55 (s, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.27 (d, J=4.9 Hz, 1H), 7.18 (s, 1H), 6.47 (s, 1H), 4.36 (s, 2H), 3.38-3.44 (m, 4H), 2.35 (s, 3H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was directly purified by reverse phase HPLC (10-75% acetonitrile in water+0.5% TFA)
  3. customThe isolated fractions were partitioned between 10% IPA/chloroform and saturated aqueous NaHCO3
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c57ccfcac9db4f3598956edb1d8d2771
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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