Hydrochloric Acid → HCID 66830604, compound

HRID 1687096Notes

Reaction equation

HRID 1687096 reaction equation
[CH2:1]([N:3]1[CH2:9][CH2:8][C:7]2[CH:10]=[C:11]([NH2:14])[CH:12]=[CH:13][C:6]=2[CH2:5][CH2:4]1)[CH3:2].Cl[C:16]1[N:21]=[C:20]([NH:22][CH2:23][CH2:24][NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[C:19]([Cl:30])=[CH:18][N:17]=1.Cl.O1CCOCC1>CC(O)C>[Cl:30][C:19]1[C:20]([NH:22][CH2:23][CH2:24][NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[N:21][C:16]([NH:14][C:11]2[CH:12]=[CH:13][C:6]3[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:9][CH2:8][C:7]=3[CH:10]=2)=[N:17][CH:18]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 189434013-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamineHCID 79633203HCID 79633203, compound

Product 1

HCID 66830604HCID 66830604, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
150 °C

Procedure

3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (90.9 mg, 0.478 mmol) and N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-ethyl]-methanesulfonamide (150 mg, 0.526 mmol, 1.1 eq) were dissolved in IPA (3 mL). 4.0 M HCl in dioxane (132 μL, 0.526 mmol, 1.1 eq) was added and the reaction was heated at 150° C. in a microwave for 6 hours. 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 0-10% MeOH/CH2Cl2 as the eluting solvent to obtain N-{2-[5-chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-ethyl}-methanesulfonamide as a white solid (90 mg, 43%). m.p.=146° C.; LCMS (m/e) 439 (M+1); 1H-NMR (d6-DMSO, 400 MHz) δ 9.06 (s, 1H), 7.93 (s, 1H), 7.45-7.40 (m, 2H), 7.18-7.08 (m, 2H), 6.97 (d, 1H, J=8.3 Hz), 3.58-3.50 (m, 2H), 3.25-3.14 (m, 2H), 2.89 (s, 3H), 2.82-2.73 (m, 4H), 2.57-2.40 (m, 6H) 1.00 (t, 3H, J=7.2 Hz).

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-aeb38e01f02541358b7ac98742777935
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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