Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → N-(trans-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclopentyl)-methanesulfonamide

HRID 1687166Notes

Reaction equation

HRID 1687166 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:13][CH2:12][CH2:11][C@H:10]2[NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[C:5]([Cl:19])=[CH:4][N:3]=1.[CH3:20][O:21][CH2:22][CH2:23][N:24]1[CH2:30][CH2:29][C:28]2[CH:31]=[C:32]([NH2:35])[CH:33]=[CH:34][C:27]=2[CH2:26][CH2:25]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[Cl:19][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:13][CH2:12][CH2:11][C@H:10]2[NH:14][S:15]([CH3:18])(=[O:17])=[O:16])=[N:7][C:2]([NH:35][C:32]2[CH:33]=[CH:34][C:27]3[CH2:26][CH2:25][N:24]([CH2:23][CH2:22][O:21][CH3:20])[CH2:30][CH2:29][C:28]=3[CH:31]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 86633888N-[trans-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclopentyl]-methanesulfonamide

Product 1

HCID 66830595N-(trans-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclopentyl)-methanesulfonamideYield 76%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

N-[trans-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclopentyl]-methanesulfonamide (60 mg, 0.185 mmol), 3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (40 mg, 0.185 mmol) and camphorsulfonic acid (64 mg, 0.278 mmol) were combined in 2 mL isopropanol and heated at 120° C. in microwave for a total of 90 min. The reaction was concentrated to be taken up in dichloromethane and washed with saturated sodium bicarbonate solution (2×30 mL). The organic layer was dried over MgSO4 and filtered. The filtrate was chromatographed on a 4 g amine capped ISCO flash column using a gradient of 0-100% ethyl acetate in hexanes. The product was collected as a foam after concentrating to afford 71 mg (76%) of a pale yellow solid. Compound 1: mp 74° C.; MS (ES+ calculated—508; found—509 M+H). 1H NMR (400 MHz, CDCl3) δ 7.95 (s, 1H), 7.06 (d, J=9 Hz, 1H), 6.96 (s, 1H), 6.38 (br s, 1H), 5.39 (d, J=6 Hz, 1H), 5.32 (s, 1H), 4.16 (m, 1H), 3.55 (t, J=6 Hz, 2H), 3.38 (s, 3H), 2.93 (m, 4H), 2.85 (s, 3H), 2.76 (m, 4H), 2.30 (m, 2H), 1.86 (m, 2H), 1.23 (t, 2H) ppm.

Workup

  1. concentrationThe reaction was concentrated
  2. washwashed with saturated sodium bicarbonate solution (2×30 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customThe filtrate was chromatographed on a 4 g amine capped ISCO flash column
  6. customThe product was collected as a foam
  7. concentrationafter concentrating

Sources & evidence

ORD record
ord-b11f274ad3964c7e802263e6c75f18c8
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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