Water → 3-Methoxy-4-[[2-methyl-6-[(2-methyl1,3-thiazol-4-yl)methyl]-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-n-(1-methyl-4-piperidyl)benzamide

HRID 2234283

Reaction equation

HRID 2234283 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:21])[C:7](=[O:20])[CH2:8][CH2:9][N:10]2[CH2:13][C:14]2[N:15]=[C:16]([CH3:19])[S:17][CH:18]=2)=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:39][CH3:40].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>CC(C)CC(O)C.CO>[CH3:40][O:39][C:24]1[CH:25]=[C:26]([CH:37]=[CH:38][C:23]=1[NH:22][C:2]1[N:12]=[C:11]2[C:5](=[CH:4][N:3]=1)[N:6]([CH3:21])[C:7](=[O:20])[CH2:8][CH2:9][N:10]2[CH2:13][C:14]1[N:15]=[C:16]([CH3:19])[S:17][CH:18]=1)[C:27]([NH:29][CH:30]1[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]1)=[O:28]

Participants

7

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 8661757710-Chloro-6-methyl-2-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2×

Product 1

HCID 686842203-Methoxy-4-[[2-methyl-6-[(2-methyl1,3-thiazol-4-yl)methyl]-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-n-(1-methyl-4-piperidyl)benzamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 79104-Methyl-2-PentanolSolvent

Conditions

Temperature
160 °C

Procedure

10-chloro-6-methyl-2-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 101; 58 mg, 0.18 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 49 mg, 0.19 mmol) and p-toluene sulphonic acid (70 mg, 0.37 mmol) were taken up in 4-methyl-2-pentanol (2 mL) and heated to 160° C. in microwave by microwave irradiation for 1 hour. The reaction mixture was dissolved in methanol (5 mL) and water (˜5 mL) and poured directly onto an SCX-3 cartridge (2 g). The cartridge was washed through with methanol (˜30 mL), before elution of products with 2M ammonia in methanol (˜30 mL). Evaporation of the ammoniacal fraction gave an amber film which was purified by reverse phase HPLC to yield the title compound as an off white solid (43 mg, 26%)

Workup

  1. washThe cartridge was washed through with methanol (˜30 mL), before elution of products with 2M ammonia in methanol (˜30 mL)
  2. customEvaporation of the ammoniacal fraction
  3. customgave an amber film which
  4. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ee0da4a715f64827a23937e02a29bf34
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Linked notes

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