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

HRID 1687146Notes

Reaction equation

HRID 1687146 reaction equation
[Cl:1][C:2]1[C:3]([NH:12][C:13]2[C:18]([Cl:19])=[CH:17][N:16]=[C:15](Cl)[N:14]=2)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][CH3:8])=[O:6].[NH2:21][C:22]1[CH:34]=[CH:33][C:25]2[N:26]([CH3:32])[C:27](=[O:31])[CH2:28][CH2:29][CH2:30][C:24]=2[CH:23]=1.Cl>CC(O)C.O1CCOCC1>[Cl:1][C:2]1[C:3]([NH:12][C:13]2[C:18]([Cl:19])=[CH:17][N:16]=[C:15]([NH:21][C:22]3[CH:34]=[CH:33][C:25]4[N:26]([CH3:32])[C:27](=[O:31])[CH2:28][CH2:29][CH2:30][C:24]=4[CH:23]=3)[N:14]=2)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][CH3:8])=[O:6]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 197602587-Amino-1-methyl-1,3,4,5-tetrahydro-benzo[B]azepin-2-oneHCID 866338732-(2,5-dichloro-pyrimidin-4-ylamino)-3-chloro-N-methyl-benzamide

Product 1

HCID 668300523-Chloro-2-[5-chloro-2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamideYield 70.1%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Procedure

3-Chloro-2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (36.0 mg, 0.109 mmol) and 7-amino-1-methyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (22.8 mg, 0.120 mmol) were slurried in iPrOH (1.5 mL) prior to adding ˜0.2 mL of 4N HCl in dioxane. This mixture was heated in a microwave reactor (sealed vessel) at 120° C. for 40 min. The mixture was extracted into DCM, washed with saturated aqueous NaHCO3 solution and the organic layer was dried by passing through a plug of Na2SO4. The resulting filtrate was evaporated and the residue purified by chromatography (silica gel, DCM/5% NH4OH-MeOH gradient). The appropriate fractions were combined and evaporated to afford a solid that was triturated with ether (2×2 mL) and yielded product (37.1 mg, 70%) as a yellow foam that had the following properties: m.p.=145-160° C.; LC/MS (ESI+): 485 (M+H); 1H-NMR (CDCl3, 400 MHz): δ 8.11 (s, 1H), 8.01 (s, 1H), 7.61 (d, 1H, J=8.1), 7.53 (d, 1H, J=8.1), 7.35-7.20 (m, 3H), 6.95 (m, 2H), 6.10 (br s, 1H), 3.38 (s, 3H), 2.83 (d, 3H, J=5.0), 2.55 (m, 2H), 2.24 (m, 2H), 2.09 (m, 2H).

Workup

  1. temperatureThis mixture was heated in a microwave reactor
  2. custom(sealed vessel) at 120° C. for 40 min
  3. extractionThe mixture was extracted into DCM
  4. washwashed with saturated aqueous NaHCO3 solution
  5. customthe organic layer was dried
  6. customThe resulting filtrate was evaporated
  7. customthe residue purified by chromatography (silica gel, DCM/5% NH4OH-MeOH gradient)
  8. customevaporated
  9. customto afford a solid
  10. customthat was triturated with ether (2×2 mL)

Sources & evidence

ORD record
ord-ce75ddf375fa403ab4a4c6604a629c43
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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