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Toluene → 4-{2-Amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-2-(ethyloxy)-6-fluorobenzonitrile

HRID 2367606
Notes
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Reaction equation

HRID 2367606 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14](F)[C:11]([C:12]#[N:13])=[C:10]([F:17])[CH:9]=2)[CH:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@H:19]2[CH:24]([CH3:26])[CH3:25])[N:3]=1.C1(C)C=CC=CC=1.[CH3:34][CH2:35][O-:36].[Na+]>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([F:17])[C:11]([C:12]#[N:13])=[C:14]([O:36][CH2:35][CH3:34])[CH:15]=2)[CH:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@H:19]2[CH:24]([CH3:26])[CH3:25])[N:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 1140TolueneHCID 2723922Sodium ethoxideHCID 585048264-{2-Amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-2,6-difluorobenzonitrile

Product 1

HCID 585045594-{2-Amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-2-(ethyloxy)-6-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent

Procedure

4-{2-Amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-2,6-difluorobenzonitrile (405 mg, 1.12 mmol) was azeotroped with toluene (2×15 mL). The residue was dissolved in 5 mL of DMF as a yellow clear solution, to which was added NaOEt (1.45 mL of a stock solution with concentration of 0.87 mmol/mL, 1.25 mmol, 1.12 equiv) at room temperature in one portion. The resulting light orange clear solution was stirred at room temperature for 20 hours. LCMS showed conversion complete. The mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 100% EtOAc, providing the title compound (310 mg) as a white solid residue. LC-MS (ES) m/z=386 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customThe residue was purified by silica gel column chromatography
  3. washelution of 1% EtOAc in CHCl3 to 100% EtOAc

Sources & evidence

ORD record
ord-3c843913bae84c38b77181357a669a78
Source dataset
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08697685B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes