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

HRID 1433015Notes

Reaction equation

HRID 1433015 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[C:30]#[N:31])[CH2:5][N:6]1[C:11](=[O:12])[CH2:10][N:9]([CH2:13][C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][C:19]([Cl:23])=[CH:18][CH:17]=3)[CH2:8][CH:7]1[C:24]([OH:26])=[O:25].[N:32]1C=NC=N[CH:33]=1.CC(O)=O>CCO>[NH2:31][C:30]1[C:29]2[C:2](=[CH:3][C:4]([CH2:5][N:6]3[C:11](=[O:12])[CH2:10][N:9]([CH2:13][C:14]4[NH:15][C:16]5[C:21]([CH:22]=4)=[CH:20][C:19]([Cl:23])=[CH:18][CH:17]=5)[CH2:8][CH:7]3[C:24]([OH:26])=[O:25])=[CH:27][CH:28]=2)[N:1]=[CH:33][N:32]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 92621,3,5-TriazineHCID 53964541(+/-)-1-(3-amino-4-cyano-benzyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid

Product 1

HCID 54503880(+/-)-1-(4-Amino-quinazolin-7-ylmethyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acidYield 76%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution containing (±)-1-(3-amino-4-cyano-benzyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid (200 mg, 0.30 mmol), 1,3,5-triazine (244 mg, 3.00 mmol), and glacial HOAc (180 mg, 3.00 mmol) in absolute EtOH (20 mL) is maintained at reflux for 16 hours. The reaction mixture is cooled to ambient temperature and the solid is collected on a Buchner funnel and washed with EtOH followed by diethyl ether. Oven-drying in vacuo provided 13 mg (76%) of the title compound as an off-white solid. 1H NMR (300 MHz, d6-DMSO) δ2.63 (m, 1H), 3.06 (d, J=16.4 Hz, 1H), 3.24-3.42 (m, 4H), 3.68 (ABq, ΔAB=34.5 Hz, JAB=14.1 Hz, 2H), 3.96 (m, 1H), 4.63 (ABq, ΔAB=400 Hz, JAB=15.8 Hz, 2H), 6.27 (s, 1H), 6.99 (dd, J=8.6, 2.0 Hz, 1H), 7.29 (d, J=8.5 Hz, 2H), 7.40 (s, 1H), 7.46 (s, 1H), 7.69 (br s, 2H), 8.10 (d, J=8.5 Hz, 1H), 8.32 (s, 1H), 11.20 (s, 1H) ppm; MS (ion spray): m/z 465 (M+H).

Workup

  1. temperatureis maintained
  2. temperatureat reflux for 16 hours
  3. customthe solid is collected on a Buchner funnel
  4. washwashed with EtOH
  5. customOven-drying in vacuo

Sources & evidence

ORD record
ord-90c20735d69a4ec9a2964822e1f01b1f
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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