4-[3-(4-Tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester → 1-[3-(4-Amino-pyridin-3-yl)-propenyl]-4-[2-(5-chloro-thiophen-2-yl)-ethenesulfonyl]-piperazin-2-one

HRID 1433000Notes

Reaction equation

HRID 1433000 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH:14]=[CH:15][CH2:16][C:17]2[CH:18]=[N:19][CH:20]=[CH:21][C:22]=2[NH:23]C(OC(C)(C)C)=O)[C:10](=[O:31])[CH2:9]1)=O)(C)(C)C.[Cl:32][C:33]1[S:37][C:36]([CH:38]=[CH:39][S:40](Cl)(=[O:42])=[O:41])=[CH:35][CH:34]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl.CC#N>[NH2:23][C:22]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[CH2:16][CH:15]=[CH:14][N:11]1[CH2:12][CH2:13][N:8]([S:40]([CH:39]=[CH:38][C:36]2[S:37][C:33]([Cl:32])=[CH:34][CH:35]=2)(=[O:42])=[O:41])[CH2:9][C:10]1=[O:31]

Participants

5

Reactant 2

HCID 538781434-[3-(4-Tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl esterHCID 544630642-(5-Chlorothiophen-2-yl)ethenesulfonyl chloride

Product 1

HCID 690284571-[3-(4-Amino-pyridin-3-yl)-propenyl]-4-[2-(5-chloro-thiophen-2-yl)-ethenesulfonyl]-piperazin-2-one

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

4-[3-(4-tert-Butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester from EXAMPLE 96, Part B (45 mg, 0.10 mmol) is dissolved in 20% TFA/CH2Cl2 and stirred at r.t. for 2 hours. The solution is concentrated to residue. The residue is dissolved in MeCN (2.5 ml) and treated with 4-methylmorphorline (0.027 ml, 0.25 mmol). 2-(5-Chloro-thiophen-2-yl)-ethenesulfonyl chloride (24 mg, 0.10 mmol), EXAMPLE 3, in MeCN (1 mL) is then added dropwise. The reaction mixture is stirred at r.t. for 1 h, then subjected to reverse phase HPLC purification, to give the title compound as white solid (0.040 g, 0.037 mmol). MS m/z 439, 441 (M+H); 1H NMR (CD3OD, 300 MHz) δ8.20 (br, 1H), 8.10 (s, 1H), 8.08 (d, 1H), 7.60 (d, 1H), 7.53 (d. 1H), 7.35 (d, 1H), 7.21 (d, 1H), 7.07 (d, 1H), 6.82 (d, 1H), 5.27 (m, 1H), 3.88 (s, 2H), 3.60-3.50 (m, 4H), 3.30 (d, 2H).

Workup

  1. concentrationThe solution is concentrated to residue
  2. dissolutionThe residue is dissolved in MeCN (2.5 ml)
  3. additiontreated with 4-methylmorphorline (0.027 ml, 0.25 mmol)
  4. stirringThe reaction mixture is stirred at r.t. for 1 h
  5. customphase HPLC purification

Sources & evidence

ORD record
ord-604b143b7931429387d19ba4afa05d09
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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