Hydrochloric Acid → 2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1686906Notes

Reaction equation

HRID 1686906 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:19])=[CH:4][N:3]=1.[CH2:20]([N:22]1[CH2:28][CH2:27][C:26]2[CH:29]=[C:30]([NH2:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)[CH3:21].Cl.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+]>COCCO.CO>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[N:7][C:2]([NH:33][C:30]2[CH:31]=[CH:32][C:25]3[CH2:24][CH2:23][N:22]([CH2:20][CH3:21])[CH2:28][CH2:27][C:26]=3[CH:29]=2)=[N:3][CH:4]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 189434013-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamineHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamide

Product 1

HCID 251582282-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
120 °C

Procedure

2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (650 mg/2.2 mmol), 3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (500 mg/2.6 mmol) and 4 N HCl in dioxane (650 μL/2.6 mmol) were suspended in 2-methoxyethanol (5 mL) and heated to 120° C. until judged complete by HPLC. The resulting tan solution was cooled to room temperature, diluted with methanol (2 mL) and treated with solid potassium carbonate (carbon dioxide evolves). The mixture was filtered and the filtrate concentrated onto silica gel and purified by column chromatography to afford 2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide as a tan solid (200 mg/20%). 1H NMR (400 MHz, CDCl3) δ 11.02 (s, 1H), 8.68 (d, J=8.1 Hz, 1H), 8.06 (s, 1H), 7.52-7.40 (m, 2H), 7.33 (s, 1H), 7.23 (s, 1H), 7.09-6.98 (m, 2H), 6.87 (s, 1H), 6.20 (s, 1H), 3.05 (d, J=3.8 Hz, 3H), 2.91 (m, 4H), 2.60 (m, 6H), 1.11 (t, J=6.9 Hz, 3H). LC/MS found 451 (M+H). mp 201° C.

Workup

  1. temperatureThe resulting tan solution was cooled to room temperature
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate concentrated onto silica gel
  4. custompurified by column chromatography

Sources & evidence

ORD record
ord-ec06fd270e334e8395dd4f6d25e95e8e
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

Loading…