tert-Butyl carbazate → HCID 86660011, compound

HRID 1966753Notes

Reaction equation

HRID 1966753 reaction equation
[Br:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:7]([C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](O)=[O:12])=[N:8][C:4]=2[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:48]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])(=[O:51])[NH:49][NH2:50].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.O>[C:53]([O:52][C:48]([N:49]([C:11](=[O:12])[C:10]1[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=1[C:7]1[N:6]([C:18]([CH3:21])([CH3:19])[CH3:20])[C:5]2[CH:22]=[CH:23][C:2]([Br:1])=[CH:3][C:4]=2[N:8]=1)[NH2:50])=[O:51])([CH3:56])([CH3:55])[CH3:54]

Participants

7

Reactant 4

HCID 70091tert-Butyl carbazateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58542046HCID 58542046, compound

Product 1

HCID 86660011HCID 86660011, compoundYield 99.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Procedure

To a round bottom flask is added 2-(5-bromo-1-tert-butyl-1H-benzimidazol-2-yl)-benzoic acid (300 mg, 0.804 mmol) in DMF (8 mL), followed by the addition of HATU (611 mg, 1.607 mmol), tert-butyl carbazate (530 mg, 4.01 mmol) and iPr2NEt (520 mg, 4.02 mmol). The reaction mixture is stirred at room temperature for 18 hours. The reaction mixture is diluted with EtOAc/water. The organic layer is separated, washed with brine, dried under anhydrous Na2SO4, filtered and concentrated. The residue is purified by silica gel flash column chromatography with 0-5% MeOH/CH2Cl2 as the eluent. The product fractions are collected and concentrated to afford N-[2-(5-bromo-1-tert-butyl-1H-benzimidazol-2-yl)-benzoyl]-hydrazinecarboxylic acid tert-butyl ester (390 mg). This material is dissolved in CH2Cl2 (3 mL), followed by the addition of trifluoroacetic acid (2 mL). The reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is concentrated to afford 2-(5-bromo-1-tert-butyl-1H-benzimidazol-2-yl)-benzoic acid hydrazide (310 mg, 100%). LCMS (ESMS): m/z 387.75, 389.75 (M++1).

Workup

  1. customThe organic layer is separated
  2. washwashed with brine
  3. customdried under anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by silica gel flash column chromatography with 0-5% MeOH/CH2Cl2 as the eluent
  7. customThe product fractions are collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1f5cf865043c487a845250299373f7b5
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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