Methanol → 3-methoxy-N-[(3R)-1-methylpyrrolidin-3-yl]-4-[(4,4,6-trimethyl-5-oxo-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]benzamide

HRID 2234305Notes

Reaction equation

HRID 2234305 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:19])[C:7](=[O:18])[C:8]([CH3:17])([CH3:16])[CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:35]=[CH:34][C:24]([C:25]([NH:27][CH:28]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29]2)=[O:26])=[CH:23][C:22]=1[O:36][CH3:37].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO>CC(C)CC(O)C>[CH3:37][O:36][C:22]1[CH:23]=[C:24]([CH:34]=[CH:35][C:21]=1[NH:20][C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:19])[C:7](=[O:18])[C:8]([CH3:17])([CH3:16])[CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])=[CH:4][N:3]=1)[C:25]([NH:27][C@@H:28]1[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29]1)=[O:26]

Participants

6

Reactant 4

HCID 887MethanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 686841234-amino-3-methoxy-N-(1-methylpyrrolidin-3-yl)benzamide2×HCID 8661755710-Chloro-4,4,6-trimethyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2×

Product 1

HCID 686853443-methoxy-N-[(3R)-1-methylpyrrolidin-3-yl]-4-[(4,4,6-trimethyl-5-oxo-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]benzamideYield 17.5%

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Procedure

10-chloro-4,4,6-trimethyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 178; 75 mg, 0.27 mmol), 4-amino-3-methoxy-N-(1-methylpyrrolidin-3-yl)benzamide (Intermediate 187; 67 mg, 0.27 mmol) and p-toluenesulphonic acid monohydrate (127 mg, 0.66 mmol) were heated at 140° C. in 4-methyl-2-pentanol (4 mL) for 2 hours. The reaction mixture was loaded onto an SCX-3 column pre-wet with methanol. The column was washed with methanol and eluted with 2% 7N ammonia/methanol to. Product containing fractions were evaporated and the residue dissolved in DMF and purified by base modified reverse phase HPLC to give the title compound as a white solid (23 mg, 17.5%).

Workup

  1. washThe column was washed with methanol
  2. washeluted with 2% 7N ammonia/methanol to
  3. additionProduct containing fractions
  4. customwere evaporated
  5. dissolutionthe residue dissolved in DMF
  6. custompurified by base modified reverse phase HPLC

Sources & evidence

ORD record
ord-f67070dc423e416f8e9555d597272c7d
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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