Hydrochloric Acid → HCID 25158228, compound

HRID 1040598Notes

Reaction equation

HRID 1040598 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 25158228HCID 25158228, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
120 °C

Procedure

31 g) 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-benzamideas 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
  5. customto afford 2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamideas a tan solid (200 mg/20%)

Sources & evidence

ORD record
ord-6610247cfdc048c080feda539b600f66
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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