Hydrochloric Acid → HCID 66830086, compound

HRID 1040791Notes

Reaction equation

HRID 1040791 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][CH:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH3:25])[C:19]([Cl:31])=[CH:18][N:17]=1.Cl.O1CCOCC1>CC(O)C>[Cl:31][C:19]1[C:20]([NH:22][CH2:23][CH:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH3:25])=[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 86633869HCID 86633869, compound

Product 1

HCID 66830086HCID 66830086, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
140 °C

Procedure

3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (86.7 mg, 0.456 mmol, 1.0 eq) and N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-1-methyl-ethyl]-methanesulfonamide (150 mg, 0.502 mmol, 1.1 eq) were dissolved in IPA (3 mL). 4.0 M HCl in dioxane (126 μL, 0.502 mmol, 1.1 eq) was added and the reaction was heated at 140° C. in a microwave for 90 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 amine capped silica gel chromatography using a gradient of 0-100% EtOAc/hex 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]-1-methyl-ethyl}-methanesulfonamide as a white foam (45 mg, 22%). LCMS (m/e) 453 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.95 (s, 1H), 7.32 (d, 1H, J=8.6 Hz), 7.06 (d, 1H, J=8.2 Hz), 6.93 (s, 1H), 5.72-5.62 (m, 1H), 5.41-5.31 (m, 1H), 3.81-3.65 (m, 2H), 3.55-3.43 (m, 1H), 2.99-2.86 (m, 4H), 2.90 (s, 3H), 2.74-2.60 (m, 4H), 2.60 (q, 2H, J=6.9 Hz), 1.32 (d, 3H, J=6.6 Hz), 1.12 (t, 3H, J=6.9 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 amine
  7. customcapped silica gel chromatography

Sources & evidence

ORD record
ord-3d6be66b968742a0a1dd2196001f0b74
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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