Trifluoroacetic acid methylene chloride → 1-(3-tert-Butyl-isoxazol-5-yl)-3-{5-fluoro-2-[1-(2-piperazin-1-yl-ethyl)-1H-indazol-5-yloxy]-benzyl}-urea

HRID 1897518Notes

Reaction equation

HRID 1897518 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[CH2:33][NH:34][C:35]([NH:37][C:38]4[O:42][N:41]=[C:40]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:39]=4)=[O:36])=[CH:22][CH:23]=3)[CH:18]=[N:17]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[C:43]([C:40]1[CH:39]=[C:38]([NH:37][C:35]([NH:34][CH2:33][C:27]2[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=2[O:25][C:21]2[CH:20]=[C:19]3[C:24](=[CH:23][CH:22]=2)[N:16]([CH2:15][CH2:14][N:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)[N:17]=[CH:18]3)=[O:36])[O:42][N:41]=1)([CH3:46])([CH3:44])[CH3:45]

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 674096104-[2-(5-{2-[3-(3-tert-Butyl-isoxazol-5-yl)-ureidomethyl]-4-fluorophenoxy}-indazol-1-yl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 426422121-(3-tert-Butyl-isoxazol-5-yl)-3-{5-fluoro-2-[1-(2-piperazin-1-yl-ethyl)-1H-indazol-5-yloxy]-benzyl}-ureaYield 80.6%

Procedure

4-[2-(5-{2-[3-(3-tert-Butyl-isoxazol-5-yl)-ureidomethyl]-4-fluorophenoxy}-indazol-1-yl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester (0.056 g, 0.088 mmol) was treated with TFA/CH2Cl2 (1:1, 2 mL) and stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure and azeotroped with toluene. The residue was diluted with ethyl acetate (40 mL) and washed with 1N NaOH and brine. The solution was concentrated under reduced pressure to afford 0.038 g of the product (80% yield). MS (ESI+) m/z 536 (M+1) detected; 1H NMR (400 mHz, CDCl3) δ 7.81 (s, 1H), 7.35 (d, 1H), 7.15 (dd, 1H), 7.08 (s, 1H), 7.05 (d, 1H), 6.88 (m, 1H), 6.76 (m, 1H), 6.28 (m, 1H), 5.99 (s, 1H), 4.46 (m, 4H), 2.86 (m, 2H), 2.79 (m, 4H), 2.43 (m, 4H), 1.26 (s, 9H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customazeotroped with toluene
  3. additionThe residue was diluted with ethyl acetate (40 mL)
  4. washwashed with 1N NaOH and brine
  5. concentrationThe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-74134bc84b9d4d12876196714d7a132e
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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