Sodium Carbonate → HCID 178451795, compound

HRID 2116910Notes

Reaction equation

HRID 2116910 reaction equation
Cl[C:2]1[N:3]=[C:4]([C:17]2[CH2:22][CH2:21][N:20]([C:23]3[C:28]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:26]=[CH:25][N:24]=3)[CH2:19][CH:18]=2)[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1.[C:33]([O:37][C:38]([N:40]1[CH2:45][CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.CCO>[F:16][C:13]([F:14])([F:15])[C:10]1[CH:11]=[CH:12][C:7]([C:6]2[NH:5][C:4]([C:17]3[CH2:22][CH2:21][N:20]([C:23]4[C:28]([C:29]([F:31])([F:32])[F:30])=[CH:27][CH:26]=[CH:25][N:24]=4)[CH2:19][CH:18]=3)=[N:3][C:2]=2[C:43]2[CH2:42][CH2:41][N:40]([C:38]([O:37][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:39])[CH2:45][CH:44]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 178506119HCID 178506119, compound

Product 1

HCID 178451795HCID 178451795, compound

Reagents, catalysts & solvents 1

HCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-(4-(4-chloro-5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)-5,6-dihydropyridin-1(2H)-yl)-3-(trifluoromethyl)pyridine (60 mg, 0.127 mmol, Example 23(c)), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (59 mg, 0.19 mmol, Chemshop), dichloro-bis(triphenyl-phosphine) palladium (II) (5 mg, 0.006 mmol, Aldrich), sodium carbonate (27 mg, 0.254 mmol), and DME/H2O/EtOH (7:3:2) solution (0.8 mL) was heated at 130° C. in a microwave synthesizer for 2 h. The reaction mixture was cooled to RT and filtered. The filter cake was washed with MeOH (2×1 mL) and the combined filtrates were concentrated in vacuo. The residue was dissolved in DMSO (1 mL) and purified by by preparative HPLC [gradient 10-85% MeCN (0.1% TFA)/H2O (0.1% TFA)]. The fractions containing the desired product were combined and treated with sat. aqueous solution of NaHCO3 (15 mL) at 0° C. for 24 h. The organic layer was separated, dried over MgSO4, and filtered. The filtrate was evaporated and the residue dried in vacuo to give the title compound as an orange solid. MS (ESI, positive ion) m/z: 620 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filter cake was washed with MeOH (2×1 mL)
  4. concentrationthe combined filtrates were concentrated in vacuo
  5. dissolutionThe residue was dissolved in DMSO (1 mL)
  6. custompurified by by preparative HPLC [gradient 10-85% MeCN (0.1% TFA)/H2O (0.1% TFA)]
  7. additionThe fractions containing the desired product
  8. additiontreated with sat. aqueous solution of NaHCO3 (15 mL) at 0° C. for 24 h
  9. customThe organic layer was separated
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customThe filtrate was evaporated
  13. customthe residue dried in vacuo

Sources & evidence

ORD record
ord-bf96084c075c44af8407fb2299419f8e
Source dataset
uspto-grants-2008_10
Patent number
US07439360B2

Reaction notes

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