Hydrochloric Acid → HCID 66830074, compound

HRID 1687113Notes

Reaction equation

HRID 1687113 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1.Cl[C:18]1[N:23]=[C:22]([NH:24][C:25]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:26]=2[C:27]([NH:29][CH3:30])=[O:28])[C:21]([Cl:36])=[CH:20][N:19]=1.Cl.O1CCOCC1>CC(O)C>[Cl:36][C:21]1[C:22]([NH:24][C:25]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:26]=2[C:27]([NH:29][CH3:30])=[O:28])=[N:23][C:18]([NH:16][C:13]2[CH:14]=[CH:15][C:8]3[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:11][CH2:10][C:9]=3[CH:12]=2)=[N:19][CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 86633872HCID 86633872, compound

Product 1

HCID 66830074HCID 66830074, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (76 mg, 0.34 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-5,N-dimethyl-benzamide (120 mg, 0.38 mmol, 1.1 eq) were dissolved in IPA (3 mL). 4.0 M HCl in dioxane (95 μL, 0.38 mmol, 1.1 eq) was added and the reaction was heated at 130° C. in a microwave for 20 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain 2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-5,N-dimethyl-benzamide as a yellow solid (99.4 mg, 59%). m.p.=210-212° C.; LCMS (m/e) 495 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 10.87 (s, 1H), 8.51 (d, 1H, J=8.5 Hz), 8.05 (d, 1H, J=1.0 Hz), 7.35 (s, 1H), 7.30-7.15 (m, 3H), 7.01 (d, 1H, J=8.1 Hz), 6.86 (s, 1H), 6.23-6.10 (m, 1H), 3.54 (t, 2H, J=5.4 Hz), 3.37 (s, 3H), 3.02 (d, 3H, J=5.0 Hz), 2.96-2.84 (m, 5H), 2.80-2.66 (m, 6H), 2.36 (s, 3H).

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. washwashed with sat. NaHCO3 (20 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by basic alumina chromatography

Sources & evidence

ORD record
ord-5f9fc8f9ee3e45279f2b50eb393dae44
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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