Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 131729608, compound

HRID 1041642Notes

Reaction equation

HRID 1041642 reaction equation
C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[CH3:16][O:17][CH2:18][CH2:19][N:20]1[CH2:26][CH2:25][C:24]2[CH:27]=[C:28]([NH2:31])[CH:29]=[CH:30][C:23]=2[CH2:22][CH2:21]1.Cl[C:33]1[N:38]=[C:37]([NH:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[S:46]([CH:49]([CH3:51])[CH3:50])(=[O:48])=[O:47])[C:36]([Cl:52])=[CH:35][N:34]=1.C(=O)([O-])[O-]>C(O)(C)C>[Cl:52][C:36]1[C:37]([NH:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[S:46]([CH:49]([CH3:51])[CH3:50])(=[O:48])=[O:47])=[N:38][C:33]([NH:31][C:28]2[CH:29]=[CH:30][C:23]3[CH2:22][CH2:21][N:20]([CH2:19][CH2:18][O:17][CH3:16])[CH2:26][CH2:25][C:24]=3[CH:27]=2)=[N:34][CH:35]=1

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 19660Carbonate IonHCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 597643782,5-dichloro-N-(2-((1-methylethyl)sulfonyl)phenyl)-4-pyrimidinamine

Product 1

HCID 131729608HCID 131729608, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

10-Camphorsulfonic acid (49 mg, 0.21 mmol) was added to 3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (44 mg, 0.20 mmol) and (2,5-Dichloro-pyrimidin-4-yl)-[2-(propane-2-sulfonyl)-phenyl]-amine (66 mg, 0.19 mmol) in Isopropyl alcohol (2 mL). The mixture was irradiated in a CEM microwave (140° C., 30 min) MP-Carbonate (2.69 mmol/g loading; 0.16 g, 0.43 mmol) was added and the mixture stirred for 1 h, then filtered, washing with 2 mL iPrOH. Brine was added, but the only ppt was NaCl. The aq. layer was extracted with EtOAc, and combined with the iPrOH, dried and conc. in vacuo. The residue was taken up in DCM with a few drops of MeOH and chromatographed (ISCO, 2×12 g, 0-10% MeOH:DCM) to afford 5-Chloro-N*2*-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine as a colorless oil (63 mg, 62%). LCMS 530 (M+H), 1H-NMR (CDCl3): 9.58 (s, 1H), 8.57 (d, 1H, J=8.4 Hz), 8.13 (s, 1H), 7.91 (d, 1H, J=7.9 Hz), 7.59 (dd, 1H, J=7.8, 8.1 Hz), 7.24 (m, 3H), 7.02 (d, 1H, J=7.9 Hz), 6.94 (s, 1H), 3.55 (m, 2H), 3.38 (s, 3H), 3.24 (sept, 1H, J=6.8 Hz), 2.88 (m, 4H), 2.73 (m, 6H), 1.31 (d, 6H, J=6.8 Hz).

Workup

  1. additionwas added
  2. filtrationfiltered
  3. washwashing with 2 mL iPrOH
  4. additionBrine was added
  5. extractionThe aq. layer was extracted with EtOAc
  6. customdried and conc. in vacuo
  7. customchromatographed (ISCO, 2×12 g, 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-537e0c9d03f74f5584b245ad9e85f945
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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