p-Toluenesulfonic acid monohydrate → 3-Ethoxy-4-[(6-methyl-5-oxo-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]benzoic acid

HRID 2234440Notes

Reaction equation

HRID 2234440 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:17])[C:7](=[O:16])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][C:20]=1[O:28][CH2:29][CH3:30].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C>[CH2:29]([O:28][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:19]=1[NH:18][C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:17])[C:7](=[O:16])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])=[CH:4][N:3]=1)[C:23]([OH:25])=[O:24])[CH3:30]

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 223974484-Amino-3-ethoxybenzoic acid2×HCID 866175432-Chloro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one2×

Product 1

HCID 686853493-Ethoxy-4-[(6-methyl-5-oxo-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]benzoic acidYield 14%

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Procedure

10-Chloro-6-methyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 10; 625 mg, 2.45 mmol), 4-amino-3-ethoxybenzoic acid (Intermediate 164; 509 mg, 2.82 mmol) and 4-toluenesulphonic acid mono hydrate (1.17 g, 6.13 mmol) were heated at 140° C. in 4-methyl-2-pentanol (15 mL) for 1.5 hours. The mixture was cooled and filtered to yield the title compound as a white solid (135 mg, 14%). The filtrate was absorbed on to an SCX column, washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and purified by column chromatography (1%-3% MeOH/DCM) to yield the title compound as a white solid (115 mg, 12%)

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered

Sources & evidence

ORD record
ord-ca35cf0764a14ad4b2ee3578880059fd
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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