Hydrochloric Acid → HCID 66830204, compound

HRID 1687178Notes

Reaction equation

HRID 1687178 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.[NH2:20][C:21]1[CH:35]=[CH:34][C:24]2[N:25]([CH3:33])[C:26](=[O:32])[CH2:27][CH2:28][C:29]([CH3:31])([CH3:30])[C:23]=2[CH:22]=1.Cl>O1CCOCC1.COCCO>[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:20][C:21]2[CH:35]=[CH:34][C:24]3[N:25]([CH3:33])[C:26](=[O:32])[CH2:27][CH2:28][C:29]([CH3:31])([CH3:30])[C:23]=3[CH:22]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 197602147-Amino-1,5,5-trimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamide

Product 1

HCID 66830204HCID 66830204, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (94 mg, 0.316 mmol), 7-Amino-1,5,5-trimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (67 mg, 0.307 mmol), 4 N HCl in dioxane (100 ul) and 2-methoxyethanol (4 mL). Heated reaction to 120° C. for 1.5 hours. Filtered off solid, then purified the solid with normal phase chromatography eluting with 97/3/1 CH2Cl2/MeOH/NH4OH to yield an off-white solid, 2-[5-Chloro-2-(1,5,5-trimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (53 mg, 35%). LCMS: m/z=479.42 (M+H+), 1H NMR (400 MHz, CDCl3) δ 11.15 (s, 1H), 8.66 (d, 1H, J=8.3 Hz), 8.14 (d, 1H, J=1.3 Hz), 7.72 (dd, 1H, J=8.7, 2.1 Hz), 7.52 (d, 1H, J=7.8 Hz), 7.45 (m, 1H), 7.33 (s, 1H), 7.11 (m, 2H), 6.97 (s, 1H), 6.23 (br s, 1H), 3.31 (s, 3H), 3.06 (d, 3H, J=4.8 Hz), 2.33 (m, 2H), 2.05 (m, 2H), 1.31 (s, 6H).

Workup

  1. temperatureHeated
  2. customreaction to 120° C. for 1.5 hours
  3. filtrationFiltered off solid
  4. custompurified the solid with normal phase chromatography
  5. washeluting with 97/3/1 CH2Cl2/MeOH/NH4OH

Sources & evidence

ORD record
ord-49725693575b405690d01ba2292297ee
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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