Methanol → 3-chloro-4-[(2-methyl-3-oxo-6-propan-2-yl-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl)amino]-N-(2-morpholin-4-ylethyl)benzamide

HRID 2234286Notes

Reaction equation

HRID 2234286 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:35]=[CH:34][C:22]([C:23]([NH:25][CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:24])=[CH:21][C:20]=1[Cl:36].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO>CC(C)CC(O)C>[Cl:36][C:20]1[CH:21]=[C:22]([CH:34]=[CH:35][C:19]=1[NH:18][C:2]1[N:12]=[C:11]2[C:5](=[CH:4][N:3]=1)[N:6]([CH3:17])[C:7](=[O:16])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:15])[CH3:14])[C:23]([NH:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)=[O:24]

Participants

6

Reactant 4

HCID 887MethanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 643181314-amino-3-chloro-N-(2-morpholin-4-ylethyl)benzamide2×HCID 866175432-Chloro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one2×

Product 1

HCID 686839563-chloro-4-[(2-methyl-3-oxo-6-propan-2-yl-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl)amino]-N-(2-morpholin-4-ylethyl)benzamideYield 15.6%

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 76; 150 mg, 0.59 mmol), 4-amino-3-chloro-N-(2-morpholin-4-ylethyl)benzamide (Intermediate 52; 168 mg, 0.59 mmol), and p-toluenesulphonic acid monohydrate (281 mg, 1.47 mmol) were heated in 4-methyl-2-pentanol (4 mL) at 140° C. for 2 hours. The reaction mixture was cooled and loaded onto an SCX-3 column pre-wet with Methanol. The column was washed with methanol to remove p-toluenesulphonic acid monohydrate and then washed with 2% 7N ammonia/methanol to elute the crude product. Product containing fractions were evaporated and the resultant material purified by reverse phase HPLC to yield the title compound as an orange gum (46 mg, 15.6%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThe column was washed with methanol
  3. customto remove p-toluenesulphonic acid monohydrate
  4. washwashed with 2% 7N ammonia/methanol
  5. washto elute the crude product
  6. additionProduct containing fractions
  7. customwere evaporated
  8. customthe resultant material purified by reverse phase HPLC

Sources & evidence

ORD record
ord-1f488b64832b42bf8c649150729292a1
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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