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

HRID 408690노트

반응식

HRID 408690 반응식
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

참가 물질

7

반응물 4

HCID 180AcetoneHCID 25517Ammonium ChlorideHCID 669371721-[6-Chloro-1-(2-methoxy-ethoxymethyl)-5-nitro-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester2회HCID 669373191-[5-Amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

생성물 1

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

시약·촉매·용매 2

HCID 23994Zinc촉매HCID 962Water용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-fef74ec791b04168b3f728f61971e400
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759345B2

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