Cesium carbonate → HCID 86664010, compound

HRID 712296Notes

Reaction equation

HRID 712296 reaction equation
[CH2:1]([C:4]1([C:32]([O-:34])=[O:33])[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18](Br)[C:19]4[S:23][C:22]([NH:24][C:25]([NH:27][CH2:28][CH3:29])=[O:26])=[N:21][C:20]=4[CH:30]=3)=[CH:12][N:11]=2)[CH2:6][CH2:5]1)[CH:2]=[CH2:3].B1(B2OC[C:46]([CH3:50])(C)CO2)OCC(C)(C)CO1.C([O-])(=O)C.[K+].Cl[C:57]1[CH:62]=[N:61][CH:60]=[CH:59][N:58]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=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.C(Cl)Cl>[CH2:1]([C:4]1([C:32]([O:34][CH2:46][CH3:50])=[O:33])[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18]([C:57]4[CH:62]=[N:61][CH:60]=[CH:59][N:58]=4)[C:19]4[S:23][C:22]([NH:24][C:25](=[O:26])[NH:27][CH2:28][CH3:29])=[N:21][C:20]=4[CH:30]=3)=[CH:12][N:11]=2)[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 73277ChloropyrazineHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 86664011HCID 86664011, compound

Product 1

HCID 86664010HCID 86664010, compoundYield 58.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-allyl-1-(5-(7-bromo-2-(3-ethylureido)benzothiazol-5-yl)pyrimidin-2-yl)piperidine-4-carboxylate (0.45 g, 0.78 mmol) in DMSO (5.0 mL) was added bis(neopentylglycolato)diboron (0.35 g, 1.57 mmol) and potassium acetate (0.11 g, 1.17 mmol) and the mixture degassed by purging N2 for 15 min followed by addition of dichloro(1,1-bis(diphenylphosphino)ferrocene)palladium (II) (0.057 g, 0.078 mmol). The reaction mixture was again degassed for 10-15 min then heated up to 80° C. for 2 h. After reaction completion the mixture was cooled to rt followed by the addition of 2-chloropyrazine (0.20 g, 1.17 mmol) and aqueous solution of Cs2CO3 (0.38 g, 1.17 mmol, dissolved in minimum amount of water) and the mixture degassed by purging N2 for 15 min followed by addition of tetrakis(triphenylphosphine)palladium (0) (0.09 g, 0.078 mmol). The reaction mixture was again degassed for 10-15 min then heated up to 80° C. for 16 h. After reaction completion, the mixture was poured into 100 mL of ice-cold water, extracted with EtOAc (3×150 mL) and the combined organic layer washed with brine, dried over Na2SO4, filtered and evaporated. The crude residue was purified over 100-200 M silica-gel using 1.50% MeOH: DCM to obtain the desired product as a beige solid (0.26 g, 58% yield). 1H NMR (DMSO-d6): δ 1.09 (t, J=7.20 Hz, 3H), 1.21 (t, J=6.80 Hz, 3H), 1.47 (m, 2H), 2.05 (m, 2H), 2.29 (m, 2H), 3.18 (m, 2H), 3.21 (q, J=7.20, 2H), 4.17 (q, J=6.80 Hz, 2H), 4.46 (m, 2H), 5.05 (m, 2H), 5.72 (m, 1H) 6.80 (br s, 1H), 8.04 (s, 1H), 8.40 (s, 1H); 8.69 (s, 1H), 8.87 (s, 1H), 8.94 (s, 2H), 9.77 (s, 1H) and 10.64 (br s, 1H).

Workup

  1. customthe mixture degassed
  2. customby purging N2 for 15 min
  3. customThe reaction mixture was again degassed for 10-15 min
  4. customAfter reaction completion the mixture
  5. temperaturewas cooled to rt
  6. customthe mixture degassed
  7. customby purging N2 for 15 min
  8. customThe reaction mixture was again degassed for 10-15 min
  9. temperaturethen heated up to 80° C. for 16 h
  10. customAfter reaction completion
  11. extractionextracted with EtOAc (3×150 mL)
  12. washthe combined organic layer washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. customevaporated
  16. customThe crude residue was purified over 100-200 M silica-gel

Sources & evidence

ORD record
ord-a2cbecc74ae24feb94be0054775bf593
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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