Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 66830245, compound

HRID 1040717Notes

Reaction equation

HRID 1040717 reaction equation
[CH3:1][NH:2][C:3]([C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:11][C:12]1[C:17]([Cl:18])=[CH:16][N:15]=[C:14](Cl)[N:13]=1)=[O:4].[CH2:20]([N:22]1[CH2:28][CH2:27][C:26]2[CH:29]=[C:30]([NH2:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)[CH3:21].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)(O)[O-].[Na+]>C(O)(C)C>[CH3:1][NH:2][C:3]([C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:11][C:12]1[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:33][C:30]2[CH:31]=[CH:32][C:25]3[CH2:24][CH2:23][N:22]([CH2:20][CH3:21])[CH2:28][CH2:27][C:26]=3[CH:29]=2)[N:13]=1)=[O:4]

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 516892Sodium BicarbonateHCID 189434013-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamineHCID 86633864HCID 86633864, compound

Product 1

HCID 66830245HCID 66830245, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

cis-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexanecarboxylic acid methylamide (45 mg, 0.15 mmol) and 3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (30 mg, 0.16 mmol) were combined with camphorsulfonic acid (60 mg, 0.25 mmol) in 3 mL isopropyl alcohol and subjected to microwave irradiation at 120° C. for 2 hours. Solid sodium bicarbonate (a pinch) was added and the mixture was stored in a freezer overnight. The mixture was subsequently concentrated and the organics were partitioned between dichloromethane and saturated sodium bicarbonate solution (100 mL each). The organic layer was separated and was dried (sodium sulfate) to afford a solid which was purified on amine functionalized silica (10% to 100% ethyl acetate:hexane gradient elution) to afford 32 mg (47%) of a white solid. Mp: 143° C.; MS: 458.59 (M+H); 1H NMR (chloroform-d): δ 7.90 (s, 1H), δ 7.35-7.24 (m, 2H), δ 7.04 (d, J=8 Hz, 1H), δ 6.82 (s, 1H), δ 6.51 (d, J=7 Hz, 1H), δ 5.64 (br s, 1H), δ 4.34 (m, 1H), δ 2.97-2.54 (m, 6H), δ 2.79 (d, J=4 Hz, 3H), δ 2.36-0.78 (m, 13H), δ 1.12 (t, J=7 Hz, 3H).

Workup

  1. customirradiation at 120° C. for 2 hours
  2. concentrationThe mixture was subsequently concentrated
  3. customthe organics were partitioned between dichloromethane and saturated sodium bicarbonate solution (100 mL each)
  4. customThe organic layer was separated
  5. dry with materialwas dried (sodium sulfate)
  6. customto afford a solid which
  7. customwas purified on amine functionalized silica (10% to 100% ethyl acetate:hexane gradient elution)

Sources & evidence

ORD record
ord-687250911b4440e2a6c706090b20f409
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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