Methyl iodide → 1-Methyl-4-nitro-1H-indazole

HRID 1267005

반응식

HRID 1267005 반응식
[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][NH:8]2)([O-:3])=[O:2].[H-].[Na+].[CH3:15]I>CN(C=O)C>[CH3:15][N:8]1[C:9]2[C:5](=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=[CH:11][CH:10]=2)[CH:6]=[N:7]1

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 180574-NitroindazoleHCID 24758Sodium hydride

생성물 1

HCID 2802131-Methyl-4-nitro-1H-indazole수율 82%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

A solution of 4-nitroindazole (prepared according to the literature procedures Davies, R. R. J.C.S., 1955, 2412-2423; Porter, H. D. Org. Synth. Collect. Vol I, 20, 73-74.) (2.01 g, 12.3 mmol) was added slowly to a cold (ice/water), stirred suspension of NaH (440 mg, 18.4 mmol) in DMF (20 mL) under N2. The mixture was stirred for 30 min, and a solution of MeI (1.91 g, 13.5 mmol) in DMF (10 mL) was then added. Workup gave 1-methyl-4-nitroindazole (1.79 g, 82%); mp (EtOAc/petroleum ether) 138-139° C. Hydrogenation of this (6.70 g, 37.9 mmol) in absolute EtOH (300 mL) in the presence of Pd/C (1.00 g) gave 4-amino-1-methylindazole (4.23 g, 76%). A mixture of 4-amino-1-methylindazole (4.10 g, 27.9 mmol) and 2-bromo-3-nitrobenzoic acid (6.86 g, 27.9 mmol) were then reacted in a mixture of isopropanol/N-methylmorpholine in the presence of copper powder and CuI as above, giving 2-[(1-methyl-1H-indazol-4-yl)amino]-3-nitrobenzoic acid (439 mg, 5 %); mp (EtOAc/n-hexane) 257-260° C.; Reductive cyclisation of 2-[(1-methyl-1H-indazol-4-yl)amino]-3-nitrobenzoic acid with NaBH4 in 2 M NaOH as above gave 3-methyl-3H-pyrazolo[4,3-a]phenazine-10-carboxylic acid as a dark yellow solid (54%); mp (acetone) 320-323° C. [(CD3)2SO] δ 4.28 (s, 3 H, NCH3), 8.07 (t, J=7.9 Hz, 1 H, H-8), 8.10 (d, J=9.6 Hz 1H, H-4 or H-5), 8.39 (d, J=9.6 Hz 1H, H-4 or H-5), 8.52-8.60 (m, 2H, H-7 and H-9), 8.76 (s, 1 H, H-2), 14.90 (br s, 1 H, COOH).

후처리

  1. customCollect
  2. addition) (2.01 g, 12.3 mmol) was added slowly to a cold (ice/water)
  3. stirringThe mixture was stirred for 30 min

출처 및 근거

ORD 기록
ord-91e44246581f4922bd938a00d259af62
출처 데이터셋
uspto-grants-2003_04
특허 번호
US06552021B2

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