Hydrochloric Acid → HCID 25158224, compound

HRID 1040647Notes

Reaction equation

HRID 1040647 reaction equation
NC1C(OC)=CC2C(=O)N(C)CCCC=2C=1.[NH2:17][C:18]1[C:23]2[C:24](=[O:30])[N:25]([CH3:29])[CH2:26][CH2:27][CH2:28][C:22]=2[CH:21]=[CH:20][C:19]=1[O:31][CH3:32].Cl.COCCO.Cl[C:40]1[N:45]=[C:44]([NH:46][C:47]2[CH:56]=[CH:55][CH:54]=[CH:53][C:48]=2[C:49]([NH:51][CH3:52])=[O:50])[C:43]([Cl:57])=[CH:42][N:41]=1>O1CCOCC1>[Cl:57][C:43]1[C:44]([NH:46][C:47]2[CH:56]=[CH:55][CH:54]=[CH:53][C:48]=2[C:49]([NH:51][CH3:52])=[O:50])=[N:45][C:40]([NH:17][C:18]2[C:23]3[C:24](=[O:30])[N:25]([CH3:29])[CH2:26][CH2:27][CH2:28][C:22]=3[CH:21]=[CH:20][C:19]=2[O:31][CH3:32])=[N:41][CH:42]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 80192-MethoxyethanolHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 67263731HCID 67263731, compoundHCID 67264171HCID 67264171, compound

Product 1

HCID 25158224HCID 25158224, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

7-Amino-8-methoxy-2-methyl-2,3,4,5-tetrahydro-benzo[c]azepin-1-one (110 mg, 0.50 mmol;) and 9-Amino-8-methoxy-2-methyl-2,3,4,5-tetrahydro-benzo[c]azepin-1-one (prepared following the procedure of 7c) were added as an unseparated mixture with 4 M of Hydrogen chloride in 1,4-Dioxane (300 uL), 2-Methoxyethanol (10 mL, 100 mmol), and 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (2 eq) charged into Radley tube. Heat 110° C. for about 3 hours, cooled to room temperature. Solid precipitated out and was filtered. This material was dissolved in dichloromethane/MeOH and treated with 3 eq. of MP-carbonate, stirred 30 min, filtered and concentrated to give 2-[5-Chloro-2-(8-methoxy-2-methyl-1-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-9-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide as an orange solid (51 mgs, 21%). Melting point: 185-187° C. 1H-NMR (DMSO, 400 MHz): 8.67 (broad m, 1H), 8.67 (s, 1H), 8.47 (broad s, 1H), 8.00 (d, J=7.0 Hz, 1H), 7.47-7.43 (m, 1H), 708-7.03 (m, 2H), 6.82 (d, J=7.8 Hz, 1H), 3.81 (s, 3H), 3.17-3.07 (m, 2H), 2.85 (s, 3H), 2.69-2.65 (m, 2H) 2.50 (s, 3H), 1.78-1.71 (m, 2H); LC/MS: 481.37 (M+H).

Workup

  1. additioncharged into Radley tube
  2. temperaturecooled to room temperature
  3. customSolid precipitated out
  4. filtrationwas filtered
  5. dissolutionThis material was dissolved in dichloromethane/MeOH
  6. additiontreated with 3 eq. of MP-carbonate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3fde88ae8e6e454da148db4442c2e9a1
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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