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 909236Notes

Reaction equation

HRID 909236 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-fd833ebbefac4ea9ac78ada42fca4583
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

Loading…