4-Methyl-2-Pentanol → 4-[(4,4-diethyl-6-methyl-5-oxo-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide

HRID 2234306Notes

Reaction equation

HRID 2234306 reaction equation
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:21])[C:7](=[O:20])[C:8]([CH2:18][CH3:19])([CH2:16][CH3:17])[CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])=[CH:4][N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:34][C:35]1[CH:50]=[CH:49][C:38]([C:39]([NH:41][CH:42]2[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]2)=[O:40])=[CH:37][C:36]=1[O:51][CH3:52].CC(C)CC(O)C>CO>[CH2:16]([C:8]1([CH2:18][CH3:19])[C:7](=[O:20])[N:6]([CH3:21])[C:5]2[C:11](=[N:12][C:2]([NH:34][C:35]3[CH:50]=[CH:49][C:38]([C:39]([NH:41][CH:42]4[CH2:43][CH2:44][N:45]([CH3:48])[CH2:46][CH2:47]4)=[O:40])=[CH:37][C:36]=3[O:51][CH3:52])=[N:3][CH:4]=2)[N:10]([CH:13]([CH3:15])[CH3:14])[CH2:9]1)[CH3:17]

Participants

6

Reactant 4

HCID 79104-Methyl-2-PentanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 8661755810-Chloro-4,4-diethyl-6-methyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2×

Product 1

HCID 686827604-[(4,4-diethyl-6-methyl-5-oxo-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

10-chloro-4,4-diethyl-6-methyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 198; 100 mg, 0.322 mmol), p-toluene sulphonic acid monohydrate (153 mg, 0.81 mmol) and 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 84 mg, 0.322 mmol) were added to 4-methyl-2-pentanol (7 mL). The reaction was heated at 120° C. over the weekend. The reaction mixture was loaded on to an SCX column (10 g), pre-wet with methanol, washed with methanol and eluted with ammonia in methanol. Product containing fractions were combined and evaporated and the resultant material purified by base modified reverse phase preparative HPLC to yield the title compound, after drying under vacuum at 70° C., as a white solid (97 mg, 56%)

Workup

  1. washwashed with methanol
  2. washeluted with ammonia in methanol
  3. additionProduct containing fractions
  4. customevaporated
  5. customthe resultant material purified by base modified reverse phase preparative HPLC

Sources & evidence

ORD record
ord-8471339384ce47ac88f209208848fcbe
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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