Hydrochloric Acid → HCID 59466300, compound

HRID 1876693Notes

Reaction equation

HRID 1876693 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH2:18]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC([O-])(C)C.[Na+].Cl>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.O.C1(C)C=CC=CC=1>[C:26]([O:25][C:24](=[O:30])[NH:23][CH:20]1[CH2:21][CH2:22][N:17]([C:2]2[CH:7]=[CH:6][C:5]([S:8](=[O:10])(=[O:9])[NH:11][C:12]3[S:13][CH:14]=[CH:15][N:16]=3)=[CH:4][CH:3]=2)[CH2:18][CH2:19]1)([CH3:29])([CH3:27])[CH3:28]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6693044-bromo-N-(1,3-thiazol-2-yl)benzene-1-sulfonamideHCID 7238334-(N-Boc-amino)piperidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 59466300HCID 59466300, compoundYield 76%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Prepared using general procedure 27. A mixture of 4-bromo-N-(thiazol-2-yl)benzenesulfonamide (500 mg, 1.57 mmol), tert-butyl piperidin-4-ylcarbamate (314 mg, 1.57 mmol), Pd2(dba)3 (43 mg, 0.05 mmol), 2-(di-t-butylphosphino)biphenyl (56 mg, 0.19 mmol), NaOtBu (423 mg, 4.4 mmol) and toluene (4 mL) was stirred at 70° C. for 3 h. After allowing the mixture to cool to RT, H2O (50 mL) and EtOAc (50 mL) were added. After acidifying with a 1 M HCl solution to pH 4, the layers were separated, and the aqueous phase was extracted 3 times with CH2Cl2 (50 mL). The combined organic extracts were dried over MgSO4 and absorbed onto Celite. Purification via silica gel chromatography using 10% MeOH in CH2Cl2 gave tert-butyl-1-(4-(N-thiazol-2-ylsulfamoyl)phenyl)piperidin-4-ylcarbamate as an off-white foam (520 mg, 76%). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=439.5; tR=2.56 min.

Workup

  1. customPrepared
  2. temperatureto cool to RT
  3. customthe layers were separated
  4. extractionthe aqueous phase was extracted 3 times with CH2Cl2 (50 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. customabsorbed onto Celite
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-96b749b6daaf4a30a0a9f4486486fade
Source dataset
uspto-grants-2012_11
Patent number
US08309587B2

Reaction notes

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