Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 66830603, compound

HRID 1041606Notes

Reaction equation

HRID 1041606 reaction equation
[NH2:1][C:2]1[C:3]([O:26][CH3:27])=[CH:4][C:5]2[CH2:11][N:10]([CH2:12][C:13]([N:15]([CH3:17])[CH3:16])=[O:14])[CH2:9][C:8](=[O:18])[N:7]([CH2:19][C:20](=[O:24])[N:21]([CH3:23])[CH3:22])[C:6]=2[CH:25]=1.Cl[C:29]1[N:34]=[C:33]([NH:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[S:42]([N:45]([CH3:47])[CH3:46])(=[O:44])=[O:43])[C:32]([Cl:48])=[CH:31][N:30]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[Cl:48][C:32]1[C:33]([NH:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[S:42](=[O:44])(=[O:43])[N:45]([CH3:46])[CH3:47])=[N:34][C:29]([NH:1][C:2]2[C:3]([O:26][CH3:27])=[CH:4][C:5]3[CH2:11][N:10]([CH2:12][C:13]([N:15]([CH3:17])[CH3:16])=[O:14])[CH2:9][C:8](=[O:18])[N:7]([CH2:19][C:20](=[O:24])[N:21]([CH3:22])[CH3:23])[C:6]=3[CH:25]=2)=[N:30][CH:31]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 467382872-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-benzenesulfonamideHCID 67264274HCID 67264274, compound

Product 1

HCID 66830603HCID 66830603, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 2-(8-amino-1-dimethylcarbamoylmethyl-7-methoxy-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-N,N-dimethyl-acetamide (80 mg, 0.21 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-benzenesulfonamide (69 mg, 0.20 mmol) in isopropanol (5 mL) was added 10-camphorsulfonic acid (123 mg, 0.53 mmol). The mixture was heated to 90° C. for 20 minutes under microwave irradiation, cooled to room temperature, and concentrated on a rotary evaporator. The residue was dissolved in dichloromethane and stirred with saturated aqueous sodium bicarbonate to neutral pH. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude product was purified by flash chromatography over silica gel (MeOH/DCM) to give 40 mg (29%) of 2-{8-[5-chloro-4-(2-dimethylsulfamoyl-phenylamino)-pyrimidin-2-ylamino]-1-dimethylcarbamoylmethyl-7-methoxy-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl}-N,N-dimethyl-acetamide as a pale yellow solid; NMR (400 MHz, CDCl3) δ 9.39 (s, 1H), 8.51 (d, J=8 Hz, 1H), 8.34 (s, 1H), 8.19 (s, 1H), 7.90 (d, J=8 Hz, 1H), 7.61 (s, 1H), 7.56 (m, 1H), 7.28 (m, 1H), 6.94 (s, 1H), 4.45 (br s, 2H), 4.08 (s, 2H), 3.93 (s, 3H), 3.54 (s, 2H), 3.35 (s, 2H), 3.10 (s, 3H), 3.00 (s, 3H), 2.96 (s, 2H), 2.91 (s, 3H), 2.79 (s, 6H); MS (m/e) 689 (M+1); mp 154° C.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated on a rotary evaporator
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washThe organic phase was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography over silica gel (MeOH/DCM)

Sources & evidence

ORD record
ord-90cc3e435a624196bd5f9d47314f4ef7
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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