Dichloromethane → 4-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2-fluorobenzonitrile
Reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@H:9]2[CH2:14][CH3:15])[N:5]=[C:4]([NH:16][CH3:17])[N:3]=1.[C:18]([C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][C:21]=1[F:29])#[N:19].C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH2:14]([C@@H:9]1[CH2:10][O:11][CH2:12][CH2:13][N:8]1[C:6]1[N:5]=[C:4]([NH:16][CH3:17])[N:3]=[C:2]([C:23]2[CH:24]=[CH:25][C:20]([C:18]#[N:19])=[C:21]([F:29])[CH:22]=2)[CH:7]=1)[CH3:15]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 140 °C
Procedure
4-Chloro-6-[(3R)-3-ethyl-4-morpholinyl]-N-methyl-2-pyrimidinamine (250 mg, 0.974 mmol) was added to a 20 mL microwave vial, followed by (4-cyano-3-fluorophenyl)boronic acid (209 mg, 1.266 mmol), PdCl2(dppf).CH2Cl2 adduct (39.8 mg, 0.049 mmol), 2M K2CO3 (1.461 mL, 2.92 mmol) and 1,4-dioxane (4 mL). The mixture was heated to 140° C. for 10 minutes. The reaction mixture was filtered through a silica plug and washed with EtOAc (3×). The filtrate was then washed with H2O (2×) and the organic layer was dried over Na2SO4 and concentrated to afford the title compound (464 mg) as a brown oil. LC-MS (ES) m/z=342 [M+H]+.
Workup
- filtrationThe reaction mixture was filtered through a silica plug
- washwashed with EtOAc (3×)
- washThe filtrate was then washed with H2O (2×)
- dry with materialthe organic layer was dried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-c1897c49e08c4fd692a5d7870e99b317
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697685B2
Reaction notes
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