Acetone → 1-(5-Amino-6-chloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid

HRID 538122Notes

Reaction equation

HRID 538122 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:15](COCCOC)[C:14]3[CH:22]=[C:23]([Cl:27])[C:24]([NH2:26])=[CH:25][C:13]=3[N:12]=2)[CH:10]=1)=[O:5])C.C(OC(C1C=NN(C2N(COCCOC)C3C=C(Cl)C([N+]([O-])=O)=CC=3N=2)C=1)=O)C.[Cl-].[NH4+].CC(C)=O>[Zn].O>[NH2:26][C:24]1[C:23]([Cl:27])=[CH:22][C:14]2[NH:15][C:11]([N:9]3[CH:10]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=[N:8]3)=[N:12][C:13]=2[CH:25]=1

Participants

7

Reactant 4

HCID 180AcetoneHCID 25517Ammonium ChlorideHCID 669371721-[6-Chloro-1-(2-methoxy-ethoxymethyl)-5-nitro-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester2×HCID 669373191-[5-Amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 444790641-(5-Amino-6-chloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acidYield 86%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Procedure

1-[5-Amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester. To a solution of 1-[6-chloro-1-(2-methoxy-ethoxymethyl)-5-nitro-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (Intermediate D from Example 40) (7.88 g, 18.6 mmol), ammonium chloride (14.9 g, 0.279 mol), acetone (75 mL), and water (15 mL) at 0° C. was added portion-wise zinc dust (12.2 g, 0.186 mol). The reaction mixture was removed from the ice bath and after 15 min, the reaction mixture was filtered through Celite®/diatomaceous earth and rinsed with EtOAc. The filtrate was concentrated and the remainder was partitioned between EtOAc (300 mL) and saturated aqueous sodium bicarbonate (55 mL). The aqueous layer was further extracted with EtOAc (2×125 mL). The combined organic layers were washed with brine (2×40 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (5-65% EtOAc/hexanes) to yield the titled compound (6.29 g, 86% yield) as a 1:1 mixture of regioisomers. MS (ESI/CI): mass calcd. for C17H20ClN5O4, 393.1; m/z found, 394.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.83 (d, J=0.6 Hz, 1H), 8.78 (d, J=0.6 Hz, 1H), 8.16 (dd, J=1.9, 0.6 Hz, 2H), 7.63 (s, 1H), 7.54 (s, 1H), 7.09 (s, 1H), 6.96 (s, 1H), 6.03 (s, 2H), 6.00 (s, 2H), 4.35 (q, J=7.1 Hz, 4H), 4.18 (s, 2H), 4.07 (s, 2H), 3.66-3.60 (m, 4H), 3.49-3.42 (m, 4H), 3.32 (s, 3H), 3.31 (s, 3H), 1.37 (t, J=7.1 Hz, 6H).

Workup

  1. customThe reaction mixture was removed from the ice bath and after 15 min
  2. filtrationthe reaction mixture was filtered through Celite®/diatomaceous earth
  3. washrinsed with EtOAc
  4. concentrationThe filtrate was concentrated
  5. customthe remainder was partitioned between EtOAc (300 mL) and saturated aqueous sodium bicarbonate (55 mL)
  6. extractionThe aqueous layer was further extracted with EtOAc (2×125 mL)
  7. washThe combined organic layers were washed with brine (2×40 mL)
  8. customdried
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified (FCC) (5-65% EtOAc/hexanes)

Sources & evidence

ORD record
ord-279347f8524242a69a899621546c8e63
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

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