Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 66829915, compound

HRID 1687106Notes

Reaction equation

HRID 1687106 reaction equation
[CH2:1]([N:3]1[CH2:9][CH2:8][C:7]2[CH:10]=[C:11]([NH2:14])[CH:12]=[CH:13][C:6]=2[CH2:5][CH2:4]1)[CH3:2].Cl[C:16]1[N:21]=[C:20]([NH:22][CH2:23][C:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])([CH3:26])[CH3:25])[C:19]([Cl:32])=[CH:18][N:17]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CC(O)C>[Cl:32][C:19]1[C:20]([NH:22][CH2:23][C:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])([CH3:26])[CH3:25])=[N:21][C:16]([NH:14][C:11]2[CH:12]=[CH:13][C:6]3[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:9][CH2:8][C:7]=3[CH:10]=2)=[N:17][CH:18]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 189434013-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamineHCID 79633335HCID 79633335, compound

Product 1

HCID 66829915HCID 66829915, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (86.7 mg, 0.456 mmol, 1.0 eq), N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-1,1-dimethyl-ethyl]-methanesulfonamide (157 mg, 0.502 mmol, 1.1 eq), and 10-camphorsulfonic acid (116 mg, 0.502 mmol, 1.1 eq) were dissolved in IPA (3 mL) and heated at 120° C. in a microwave for 60 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain N-{2-[5-chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-1,1-dimethyl-ethyl}-methanesulfonamide as a pink solid (73 mg, 34%). m.p.=118-121° C.; LCMS (m/e) 467 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.95 (s, 1H), 7.34-7.26 (m, 2H), 7.05 (d, 1H, J=7.7 Hz), 6.98 (s 1H), 5.82-5.72 (m, 2H), 3.65 (d, 1H, J=6.4 Hz), 2.94 (s, 3H), 3.00-2.85 (m, 4H), 2.73-2.55 (m, 4H), 2.58 (q, 2H, J=6.6 Hz), 1.44 (s, 6H), 1.11 (t, 3H, J=7.1 Hz).

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. washwashed with sat. NaHCO3 (20 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by basic alumina chromatography

Sources & evidence

ORD record
ord-45a2618fee8847c58d3c8c80e49ff2df
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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