Hydrochloric Acid → N-[(6-Amino-2,4-dimethyl(3-pyridyl))methyl]-2-(3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl)acetamide Hydrochloride Salt

HRID 1060217Notes

Reaction equation

HRID 1060217 reaction equation
Cl.O1CCOCC1.[F:8][C:9]([F:47])([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:10][NH:11][C:12]1[C:13]([F:40])=[C:14]([CH2:19][C:20]([NH:22][CH2:23][C:24]2[C:25]([CH3:39])=[N:26][C:27]([NH:31]C(OC(C)(C)C)=O)=[CH:28][C:29]=2[CH3:30])=[O:21])[C:15]([Cl:18])=[CH:16][CH:17]=1>>[ClH:18].[NH2:31][C:27]1[N:26]=[C:25]([CH3:39])[C:24]([CH2:23][NH:22][C:20](=[O:21])[CH2:19][C:14]2[C:15]([Cl:18])=[CH:16][CH:17]=[C:12]([NH:11][CH2:10][C:9]([F:8])([F:47])[C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:13]=2[F:40])=[C:29]([CH3:30])[CH:28]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 224753562-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}-n-({6-[(tert-butoxy)carbonylamino]-2,4-dimethyl(3-pyridyl)}methyl) acetamide

Product 1

HCID 22475322N-[(6-Amino-2,4-dimethyl(3-pyridyl))methyl]-2-(3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl)acetamide Hydrochloride SaltYield 153.4%

Procedure

A solution of HCl in 1,4-dioxane (4.0 M, 0.5 mL, 2 mmol) was added to 2-{3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}-N-({6-[(tert-butoxy) carbonylamino]-2,4-dimethyl(3-pyridyl)}methyl) acetamide (18.5 mg, 32 μmol), as prepared in the preceding step. After stirring at ambient temperature for 3 hours, solid precipitated. A solution of MeOH (0.1 mL) in DCM (1 mL) was added to dissolve the solid. After stirring for another 2 hours the reaction was concentrated to give a brown solid, that was washed with ether and DCM and dried in vacuo to produce the title compound (12.6 mg, 77% yield) as a pale brown solid. 1H-NMR (400 MHz, CD3OD) δ 8.40 (bs, 1H),7.53-7.51 (m, 2H), 7.47-7.40 (m, 3H), 6.93 (dd, J=8.8, 1.3 Hz, 1H), 6.68 (s, 1H), 6.64 (t, J=9.1 Hz, 1H), 4.31 (d, J=4.6 Hz, 2H), 3.81 (t, J=13.8 Hz, 21H), 3.67 (d, J=1.2 Hz, 2H), 2.54 (s, 3H), 2.42 (s, 3H). Mass spectrum (LCMS, ESI) calc'd for C24H25ClF3N4O (M+H): 477.2. Found: 477.5.

Workup

  1. customas prepared in the preceding step
  2. customsolid precipitated
  3. additionA solution of MeOH (0.1 mL) in DCM (1 mL) was added
  4. dissolutionto dissolve the solid
  5. stirringAfter stirring for another 2 hours the reaction
  6. concentrationwas concentrated
  7. customto give a brown solid, that
  8. washwas washed with ether and DCM
  9. customdried in vacuo

Sources & evidence

ORD record
ord-073adb9aa0b84f798c76b7355c198587
Source dataset
uspto-grants-2003_02
Patent number
US06521663B2

Reaction notes

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