Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 56663174, compound

HRID 1041632Notes

Reaction equation

HRID 1041632 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[N:15]([CH2:20][CH3:21])[S:16]([CH3:19])(=[O:18])=[O:17])[C:5]([Cl:22])=[CH:4][N:3]=1.[CH3:23][O:24][C:25]1[C:26]([NH2:40])=[CH:27][C:28]2[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][O:37][CH3:38])[CH2:31][CH2:30][C:29]=2[CH:39]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)([O-])[O-]>C(O)(C)C>[Cl:22][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[N:15]([CH2:20][CH3:21])[S:16]([CH3:19])(=[O:18])=[O:17])=[N:7][C:2]([NH:40][C:26]2[C:25]([O:24][CH3:23])=[CH:39][C:29]3[CH2:30][CH2:31][N:32]([CH2:35][CH2:36][O:37][CH3:38])[CH2:33][CH2:34][C:28]=3[CH:27]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 19660Carbonate IonHCID 574161508-Methoxy-3-(2-methoxyethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-amineHCID 86634062HCID 86634062, compound

Product 1

HCID 56663174HCID 56663174, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-N-ethyl-methanesulfonamide (99 mg, 0.27 mmol), 8-Methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (67 mg, 0.27 mmol), and 10-Camphorsulfonic acid (94 mg, 0.40 mmol) in Isopropyl alcohol (4 mL) was heated in a microwave vial for 90 min at 120° C. Upon cooling, the mixture was treated with MP-Carbonate (2.69 mmol/g loading; 0.35 g, 0.94 mmol) for 1 h, was filtered and was concentrated in vacuo onto Celite. Chromatography (ISCO, 12 g silica gel, 40-80% EtOAc:Hex) afforded N-((1R,2R)-2-{5-Chloro-2-[8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-N-ethyl-methanesulfonamide as an off white foam (70 mg, 40%). LCMS: 581 (M+H); 1H-NMR, CDCl3: 8.18 (s, 1H), 7.90 (s, 1H), 7.35 (s, 1H), 6.64 (s, 1H), 5.86 (s, 1H), 4.05 (m, 1H), 3.87 (s, 3H), 3.80 (m, 3H), 3.54 (m, 1H), 3.3 (s, 3H), 3.25 (m, 3H), 2.6-2.9 (m, 10H), 2.45 (m, 1H), 1.94 (m, 2H), 1.82 (m, 1H), 1.7 (m, 1H), 1.1-1.5 (m, 7H).

Workup

  1. temperatureUpon cooling
  2. filtrationwas filtered
  3. concentrationwas concentrated in vacuo onto Celite

Sources & evidence

ORD record
ord-1993c344b35340398e817dc7317fbfb4
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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