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

HRID 1521362Notes

Reaction equation

HRID 1521362 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-621a6883469d4a7194db3826cbdd393a
Source dataset
uspto-grants-2015_07
Patent number
US09073923B2

Reaction notes

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