Hydrochloric Acid → N-[(6-Amino-2-methyl(3-pyridyl))methyl]-2-[3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}acetamide Hydrochloride Salt

HRID 1060215Notes

Reaction equation

HRID 1060215 reaction equation
[F:1][C:2]([F:39])([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:3][NH:4][C:5]1[C:6]([F:32])=[C:7]([CH2:12][C:13]([NH:15][CH2:16][C:17]2[C:18]([CH3:31])=[N:19][C:20]([NH:23]C(OC(C)(C)C)=O)=[CH:21][CH:22]=2)=[O:14])[C:8]([Cl:11])=[CH:9][CH:10]=1.Cl.O1CCOCC1>>[ClH:11].[NH2:23][C:20]1[N:19]=[C:18]([CH3:31])[C:17]([CH2:16][NH:15][C:13](=[O:14])[CH2:12][C:7]2[C:8]([Cl:11])=[CH:9][CH:10]=[C:5]([NH:4][CH2:3][C:2]([F:1])([F:39])[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:6]=2[F:32])=[CH:22][CH:21]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 224753292-[3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl]-N-({6-[(tert-butoxy)carbonylamino]-2-methyl(3-pyridyl)}methyl) Acetamide

Product 1

HCID 22475324N-[(6-Amino-2-methyl(3-pyridyl))methyl]-2-[3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}acetamide Hydrochloride SaltYield 181.3%

Procedure

To a flask charged with 2-{3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}-N-({6- [(tert-butoxy)carbonylamino]-2-methyl(3-pyridyl)}methyl)acetamide (770 mg, 1.37 mmol), as prepared in the preceding step, was added a solution of HCl in 1,4-dioxane (5 mL, 20 mmol, 4.0 M). After stirring at ambient temperature for 1.5 hours, some solid precipitated. A solution of MeOH (1 mL) in DCM (3 mL) was added to dissolve the solid, and the mixture was stirred for additional 4 hours. The solvents were removed, and the resulting residue was washed with DCM (5 mL×2), ether (8 mL×2), and dried in high vacuum to give the title compound (620 mg, 91% yield) as a pale brown solid. 1H-NMR (400 MHz, CD3OD) δ 7.81 (d, J=9.1 Hz, 1H), 7.54-7.51 (m, 2H), 7.45-7.42 (m, 3H), 6.94 (dd, J=8.9, 1.6 Hz, 1H), 6.80 (d, J=9.1 Hz, 1H), 6.65 (t, J=9.1 Hz, 1H), 4.25 (s, 2H), 3.81 (t, J=13.8 Hz, 2H), 3.70 (d, J=1.8 Hz, 2H), 2.50 (s, 3H). Mass spectrum (LCMS, ESI) calcd for C23H23ClF3N4O (M+H): 463.1. Found: 463.7.

Workup

  1. customas prepared in the preceding step
  2. customsome solid precipitated
  3. additionA solution of MeOH (1 mL) in DCM (3 mL) was added
  4. dissolutionto dissolve the solid
  5. stirringthe mixture was stirred for additional 4 hours
  6. customThe solvents were removed
  7. washthe resulting residue was washed with DCM (5 mL×2), ether (8 mL×2)
  8. customdried in high vacuum

Sources & evidence

ORD record
ord-358fc816fdb64893aa820b44706bf2f6
Source dataset
uspto-grants-2003_02
Patent number
US06521663B2

Reaction notes

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