Sodium Bicarbonate → (3S)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-3-piperidinecarboxylic acid
Reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([OH:16])=[O:15])[CH2:9]2)[CH:5]=[C:4](Cl)[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([O-])(O)=O.[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([OH:16])=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:23]2[CH:24]=[CH:25][C:20]([C:18]#[N:19])=[C:21]([F:29])[CH:22]=2)[N:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 140 °C
Procedure
A mixture of (3S)-1-(2-amino-6-chloro-4-pyrimidinyl)-3-piperidinecarboxylic acid (1.9 g, 7.40 mmol), (4-cyano-3-fluorophenyl)boronic acid (1.465 g, 8.88 mmol) and NaHCO3 (0.622 g, 7.40 mmol) in 1,4-dioxane (10 mL) and water (2.5 mL) was stirred for 10 minutes under nitrogen. Pd(Ph3P)4 (0.171 g, 0.148 mmol) was added, and the microwave tube was heated at 140° C. for 50 minutes in microwave. LCMS showed 50% desired product. The reaction was then heated at 100° C. overnight. The yellow mixture was filtered and dried. The solid was washed with Et2O (3×), and dried. The filtrate was poured into water. The formed solid was filtered and dried. The solids were combined to afford the title compound (1.8 g) as a yellow solid. LC-MS (ES) m/z=342 [M+H]+.
Sources & evidence
- ORD record
- ord-72ac8c3518344d1593731327e7fff210
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697685B2
Reaction notes
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