p-Toluenesulfonic acid monohydrate → HCID 68683836, compound

HRID 2234302Notes

Reaction equation

HRID 2234302 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([NH:6][C:7](=[O:20])[C:8]([CH3:19])([CH3:18])[CH2:9][N:10]2[CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:40]=[CH:39][C:25]([C:26]([NH:28][CH:29]2[CH2:36][C@H:35]3[N:37]([CH3:38])[C@H:31]([CH2:32][CH2:33][CH2:34]3)[CH2:30]2)=[O:27])=[CH:24][C:23]=1[O:41][CH3:42].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C.CO.O>[CH:13]1([N:10]2[CH2:9][C:8]([CH3:19])([CH3:18])[C:7](=[O:20])[NH:6][C:5]3[C:11]2=[N:12][C:2]([NH:21][C:22]2[CH:40]=[CH:39][C:25]([C:26]([NH:28][CH:29]4[CH2:36][C@H:35]5[N:37]([CH3:38])[C@H:31]([CH2:32][CH2:33][CH2:34]5)[CH2:30]4)=[O:27])=[CH:24][C:23]=2[O:41][CH3:42])=[N:3][CH:4]=3)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 581540122-Chloro-9-cyclopentyl-7,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one2×HCID 67159898HCID 67159898, compound2×

Product 1

HCID 68683836HCID 68683836, compoundYield 54.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 79104-Methyl-2-PentanolSolvent

Conditions

Temperature
160 °C

Procedure

10-chloro-2-cyclopentyl-4,4-dimethyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 127; 62 mg, 0.21 mmol) and 4-amino-3-methoxy-N-[(1S,5R)-9-methyl-9-azabicyclo[3.3.1]non-7-yl]benzamide (Intermediate 161; 63 mg, 0.21 mmol) were taken up in 4-methyl-2-pentanol (2 mL) and p-toluenesulphonic acid monohydrate (81 mg, 0.42 mmol) added. The reaction mixture was heated at 160° C. by microwave irradiation for 60 minutes. The cooled reaction mixture was treated with a mixture of methanol & water (5:2 v/v, 7 mL). The resultant solution was loaded onto an SCX-3 cartridge (5 g) pre-wet with methanol. The cartridge was washed through with Methanol (˜40 mL). Products were then eluted with 2M ammonia in methanol (˜30 mL). The ammoniacal solution was evaporated and the resultant material was purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (64 mg, 54%).

Workup

  1. customThe cooled reaction mixture
  2. washThe cartridge was washed through with Methanol (˜40 mL)
  3. washProducts were then eluted with 2M ammonia in methanol (˜30 mL)
  4. customThe ammoniacal solution was evaporated
  5. customthe resultant material was purified by base modified reverse phase preparative HPLC

Sources & evidence

ORD record
ord-94d91188bc9b48bc81ec1f0992f5187b
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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