Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 3-{2-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-5-morpholin-4-yl-phenoxy}-propionitrile

HRID 1041655Notes

Reaction equation

HRID 1041655 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:16][C:10]=2[O:11][CH2:12][CH2:13][C:14]#[N:15])[C:5]([Cl:26])=[CH:4][N:3]=1.[NH2:27][C:28]1[CH:29]=[CH:30][C:31]2[C:37]([CH3:39])([CH3:38])[CH2:36][CH2:35][C:34](=[O:40])[NH:33][C:32]=2[CH:41]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)(O)[O-].[Na+]>C(O)(C)C.O>[Cl:26][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:16][C:10]=2[O:11][CH2:12][CH2:13][C:14]#[N:15])=[N:7][C:2]([NH:27][C:28]2[CH:29]=[CH:30][C:31]3[C:37]([CH3:38])([CH3:39])[CH2:36][CH2:35][C:34](=[O:40])[NH:33][C:32]=3[CH:41]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 516892Sodium BicarbonateHCID 574160628-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 866340643-[2-(2,5-Dichloro-pyrimidin-4-ylamino)-5-morpholin-4-yl-phenoxy]-propionitrile

Product 1

HCID 668306863-{2-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-5-morpholin-4-yl-phenoxy}-propionitrileYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

3-[2-(2,5-Dichloro-pyrimidin-4-ylamino)-5-morpholin-4-yl-phenoxy]-propionitrile (88 mg, 0.22 mmol), 8-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (46 mg, 0.22 mmol), and 10-Camphorsulfonic acid (7.8 mg, 0.033 mmol) in Isopropyl alcohol (2 mL) was irradiated in a CEM microwave (140° C., 30 min). The mixture was diluted with 2 mL water and 0.25 mL satd. sodium bicarbonate, stirred for 10 min, then cooled for 1 h. The resultant solids were collected, washing with water, drying in vacuo to afford 3-{2-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-5-morpholin-4-yl-phenoxy}-propionitrile as dark yellow solids (94 mg, 75%). MP: 150-156° C., LCMS 562 (M+H), 1H-NMR (CDCl3): 8.00 (d, 1H, J=8.9 Hz), 7.98 (s, 1H), 7.55 (s, 1H), 7.30 (d, 1H, J=8.4 Hz), 7.04 (s, 1H), 6.96 (d, 1H, J=8.4 Hz), 6.61 (d, 1H, J=8.8 Hz), 6.52 (s, 1H), 4.27 (t, 2H, J=6.2 Hz), 3.90 (t, 4H, J=4.7 Hz), 3.23 (t, 4H, J=4.7 Hz), 2.87 (t, 2H, J=6.2 Hz), 2.38 (t, 2H, J=7.0 Hz), 2.09 (t, 2H, J=7.0 Hz).

Workup

  1. temperaturecooled for 1 h
  2. customThe resultant solids were collected
  3. washwashing with water
  4. customdrying in vacuo

Sources & evidence

ORD record
ord-d9f4e1155c94419787d73b1a1aa6fa78
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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