Acetyl chloride → HCID 86669267, compound

HRID 2366923

Reaction equation

HRID 2366923 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3].CC(OC(=O)NC1C2C(=CC=C(B3OC(C)(C)C(C)(C)O3)C=2)N(C(=O)C)C(C)C1)C.C(=O)([O-])[O-].[K+].[K+].I[C:68]1[N:69]=[CH:70][C:71]([N:74]2[CH2:79][CH2:78][N:77](C(OC(C)(C)C)=O)[CH2:76][CH2:75]2)=[N:72][CH:73]=1.C([Cl:90])(=O)C>C(O)C.C1(C)C=CC=CC=1.CO.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>[ClH:90].[C:26]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:68]3[CH:73]=[N:72][C:71]([N:74]4[CH2:75][CH2:76][NH:77][CH2:78][CH2:79]4)=[CH:70][N:69]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5](=[O:30])[O:4][CH:2]([CH3:3])[CH3:1])[CH2:8][C@@H:9]1[CH3:29])(=[O:28])[CH3:27]

Participants

10

Reactant 5

HCID 6367Acetyl chlorideHCID 11430Potassium CarbonateHCID 681853941-Methylethyl [(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamateHCID 774200021-Methylethyl [1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamateHCID 866692291,1-Dimethylethyl 4-(5-iodo-2-pyrazinyl)-1-piperazinecarboxylate

Product 1

HCID 86669267HCID 86669267, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

In a carousel tube, 1-methylethyl[(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 12) (80 mg, 0.192 mmol), potassium carbonate (53.1 mg, 0.384 mmol), tetrakis(triphenylphosphine)palladium(0) (11.10 mg, 9.61 μmol) and 1,1-dimethylethyl 4-(5-iodo-2-pyrazinyl)-1-piperazinecarboxylate (for a preparation see Intermediate 13) (90 mg, 0.231 mmol) were dissolved in Ethanol (0.5 mL) and Toluene (0.5 mL). The tube was placed in a carousel and heated under nitrogen for 18 hr at 90° C. The reaction mixture was filtered and the solvent evaporated before being taken up in DCM and purified by SP4 on a 12+M silica cartridge using a gradient of 10-60% EtOAc in cyclohexane. Appropriate fractions were collected and concentrated. The samples were dissolved in 1:1 MeOH:DMSO 1 mL and purified by MDAP. The solvent was evaporated in vacuo to give the protected product. The sample was then dissolved in MeOH and acetyl chloride (0.015 mL, 0.211 mmol) was added. The solvent was then evaporated via nitrogen blow down to give the final product (63.9 mg) as an HCl salt. LCMS (Method C): Rt=0.65, MH+=453

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent evaporated
  3. custompurified by SP4 on a 12+M silica cartridge
  4. customAppropriate fractions were collected
  5. concentrationconcentrated
  6. dissolutionThe samples were dissolved in 1:1 MeOH
  7. customDMSO 1 mL and purified by MDAP
  8. customThe solvent was evaporated in vacuo
  9. customto give the protected product
  10. customThe solvent was then evaporated via nitrogen

Sources & evidence

ORD record
ord-3904d69bd31a452a88aaed331a57edca
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Linked notes

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