1,4-Dioxane hydrochloride → 1-(3-amino-6-ethoxy-7-fluoro-1H-indazol-5-yl)-3-(3-fluorobenzyl)urea

HRID 222384Notes

Reaction equation

HRID 222384 reaction equation
C(OC([NH:8][C:9]1[C:17]2[C:12](=[C:13]([F:33])[C:14]([O:30][CH2:31][CH3:32])=[C:15]([NH:18][C:19]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)=[O:20])[CH:16]=2)[N:11](C(OC(C)(C)C)=O)[N:10]=1)=O)(C)(C)C.Cl.O1CCOCC1>>[NH2:8][C:9]1[C:17]2[C:12](=[C:13]([F:33])[C:14]([O:30][CH2:31][CH3:32])=[C:15]([NH:18][C:19]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)=[O:20])[CH:16]=2)[NH:11][N:10]=1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 57908848Tert-butyl 3-tert-butoxycarbonylamino-6-ethoxy-7-fluoro-5-[3-(3-fluorobenzyl)ureido]indazole-1-carboxylate

Product 1

HCID 250100441-(3-amino-6-ethoxy-7-fluoro-1H-indazol-5-yl)-3-(3-fluorobenzyl)ureaYield 31%

Procedure

4.4 250 mg of tert-butyl 3-tert-butoxycarbonylamino-6-ethoxy-7-fluoro-5-[3-(3-fluorobenzyl)ureido]indazole-1-carboxylate (4.5 mmol) are stirred for 16 hours with 5 ml of HCl/dioxane (4 M). The batch is concentrated and evaporated three times with 20 ml of toluene each time in a rotary evaporator. The residue is purified by column chromatography on silica gel (eluent:ethyl acetate:methanol 9:1). Evaporation of the corresponding fractions gives 50 mg of 1-(3-amino-6-ethoxy-7-fluoro-1H-indazol-5-yl)-3-(3-fluorobenzyl)urea (“A14”) (31%), MS-FAB (M+H+)=362.

Workup

  1. concentrationThe batch is concentrated
  2. customevaporated three times with 20 ml of toluene each time
  3. customin a rotary evaporator
  4. customThe residue is purified by column chromatography on silica gel (eluent:ethyl acetate:methanol 9:1)
  5. customEvaporation of the corresponding fractions

Sources & evidence

ORD record
ord-a7ed9adaa2cc4c2e91ff49d5e17baf11
Source dataset
uspto-grants-2012_06
Patent number
US08207210B2

Reaction notes

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