4-[4-[[4-Amino-5-(3-fluorobenzoyl)-2-thiazolyl]amino]phenyl]-1-piperazinecarboxylic acid, 1,1-dimethylethyl ester → [4-Amino-2-[[4-(1-piperazinyl)phenyl]amino]-5-thiazolyl](3-fluorophenyl)methanone

HRID 2213907Notes

Reaction equation

HRID 2213907 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)[S:5][C:6]=1[C:7](=[O:15])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=1.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[NH2:1][C:2]1[N:3]=[C:4]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([N:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)=[CH:21][CH:22]=2)[S:5][C:6]=1[C:7]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=1)=[O:15]

Participants

3

Reactant 2

HCID 101176544-[4-[[4-Amino-5-(3-fluorobenzoyl)-2-thiazolyl]amino]phenyl]-1-piperazinecarboxylic acid, 1,1-dimethylethyl esterHCID 21863450Trifluoroacetic acid methylene chloride

Product 1

HCID 9800951[4-Amino-2-[[4-(1-piperazinyl)phenyl]amino]-5-thiazolyl](3-fluorophenyl)methanoneYield 100.6%

Procedure

A mixture of 4-[4-[[4-amino-5-(3-fluorobenzoyl)-2-thiazolyl]amino]phenyl]-1-piperazinecarboxylic acid, 1,1-dimethylethyl ester (75 mg, 0.15 mmol) (from Step A above) and a solution of TFA/CH2Cl2 (1:1; 1.5 mL) was gently shaken for 1.5 h. The solution was evaporated in vacuo. To the residue was added resin-bound N,N-diisopropylethylamine (2.5 g, loading capacity: 3.8 mmol/g from Argonaut, Inc.) and CH2Cl2 (15 mL). After shaking overnight, the mixture was filtered and washed successively with CH3OH and CH2Cl2. The solvent was evaporated in vacuo and the residue was triturated by diethyl ether/hexanes (1/9) to afford [4-amino-2-[[4-(1-piperazinyl)phenyl]amino]-5-thiazolyl](3-fluorophenyl)methanone (60 mg, 100%).

Workup

  1. customThe solution was evaporated in vacuo
  2. additionTo the residue was added resin-bound N,N-diisopropylethylamine (2.5 g, loading capacity: 3.8 mmol/g from Argonaut, Inc.) and CH2Cl2 (15 mL)
  3. filtrationthe mixture was filtered
  4. washwashed successively with CH3OH and CH2Cl2
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was triturated by diethyl ether/hexanes (1/9)

Sources & evidence

ORD record
ord-fcabc2c1d9cf465b9bdd00c79386e7f2
Source dataset
uspto-grants-2006_09
Patent number
US07105670B2

Reaction notes

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