Trifluoroacetic acid → (+/-)-1-(4-Amino-quinazolin-7-ylmethyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid methyl ester

HRID 1433013Notes

Reaction equation

HRID 1433013 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:18][N:19]1[CH2:24][C:23](=[O:25])[N:22]([CH2:26][C:27]2[CH:36]=[C:35]3[C:30]([C:31]([NH2:37])=[N:32][CH:33]=[N:34]3)=[CH:29][CH:28]=2)[CH:21]([C:38]([O:40][CH3:41])=[O:39])[CH2:20]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:41][O:40][C:38]([CH:21]1[CH2:20][N:19]([CH2:18][C:9]2[NH:8][C:16]3[C:11]([CH:10]=2)=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[CH2:24][C:23](=[O:25])[N:22]1[CH2:26][C:27]1[CH:36]=[C:35]2[C:30]([C:31]([NH2:37])=[N:32][CH:33]=[N:34]2)=[CH:29][CH:28]=1)=[O:39]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 53785442(+/-)-2-[4-(4-Amino-quinazolin-7-ylmethyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester

Product 1

HCID 67108957(+/-)-1-(4-Amino-quinazolin-7-ylmethyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid methyl esterYield 69.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing (±)-2-[4-(4-amino-quinazolin-7-ylmethyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester (26 mg, 0.03 mmol) in CH2Cl2 (4 mL) is added trifluoroacetic acid (1 mL) at ambient temperature. After 4 h, the reaction mixture is concentrated in vacuo and then dissolved in water/CH3CN and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 10 mg (47%) of the title compound as a white solid. 1H NMR (300 MHz, d6-DMSO) δ2.62 (m, 1H), 3.05-3.51 (m, 4H), 3.59 (s, 3H), 3.81 (d, J=14.0 Hz, 1H), 4.26 (m, 1H), 4.69 (ABq, ΔAB=310 Hz, JAB=16.4 Hz, 2H), 6.26 (s, 1H), 7.02 (dd, J=8.6, 2.0 Hz, 1H), 7.31 (d, J=8.6 Hz, 1H), 7.49 (d, J=2.0 Hz, 1H), 7.52 (s, 1H), 7.61 (d, J=8.7 Hz, 1H), 8.30 (d, J=8.6 Hz, 1H), 8.47 (s, 1H), 8.77 (s, 1H), 9.69 (br s, 2H), 11.17 (s, 1H) ppm; MS (ion spray): m/z 479 (M+H).

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. dissolutiondissolved in water/CH3CN
  3. custompurified by reverse-phase HPLC [Buffer A: water

Sources & evidence

ORD record
ord-3e73c01397324be58923e9180dcf3eb3
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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