Dichloromethane methanol → N-[(6-Amino-2-methyl(3-pyridyl))methyl]-2-(3-{[2,2-difluoro-2-(4-fluoronaphthyl)ethyl]amino]-6-chloro-2-fluorophenyl)acetamide hydrochloride salt

HRID 2184208Notes

Reaction equation

HRID 2184208 reaction equation
[F:1][C:2]([F:44])([C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]([F:43])=[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.CO.C(Cl)Cl>Cl.C(Cl)Cl>[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:44])[C:33]3[C:42]4[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:36]([F:43])=[CH:35][CH:34]=3)[C:6]=2[F:32])=[CH:22][CH:21]=1

Participants

5

Reactant 2

HCID 21226129Dichloromethane methanolHCID 224753192-(3-{[2,2-Difluoro-2-(4-fluoronaphthyl)ethyl]amino]-6-chloro-2-fluorophenyl)-N-({6-[(tert-butoxy)carbonylamino]-2-methyl(3-pyridyl)) methyl)acetamide

Product 1

HCID 22475337N-[(6-Amino-2-methyl(3-pyridyl))methyl]-2-(3-{[2,2-difluoro-2-(4-fluoronaphthyl)ethyl]amino]-6-chloro-2-fluorophenyl)acetamide hydrochloride saltYield 136.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(3-{[2,2-difluoro-2-(4-fluoronaphthyl)ethyl]amino}-6-chloro-2-fluorophenyl)-N-({6-[(tert-butoxy)carbonylamino]-2-methyl(3-pyridyl)}methyl)acetamide (10 mg, 16 μmol), as prepared in the preceding step, in HCl (0.5 mL, 4.0 M in 1,4-dioxane) was stirred for 2 hours at ambient temperature. A solution of MeOH/DCM (25%, 0.4 mL) was added, and the mixture continued to stir overnight. The solvents were evaporated, and the resulting brown residue was flash chromatographed on silica gel eluting with MeOH/DCM (2.5, 5, and 10%) to give a solid product. It was treated with HCl solution (0.01 mL, 4.0 M in 1,4-dioxane, 40 μmol) in DCM (0.5 mL), stirred for 5 minutes, and the solvents evaporated to give the title compound (6.2 mg, 69% yield) as a white solid. 1H-NMR (400 MHz, CD3OD) δ 8.26 (d, J=8.4 Hz, 1H), 8.17-8.14 (m, 1H), 7.80 (d, J=9.1 Hz, 1H), 7.73-7.64 (m, 4H), 7.20 (dd, J=10.0, 8.3 Hz, 1H), 6.82-6.79 (m, 1H), 6.49 (t, J=9.1 Hz, 1H), 4.24 (s, 2H), 4.10-4.02 (m, 2H), 3.66 (d, J=2.3 Hz, 2H), 2.49 (s, 3H). Mass spectrum (LCMS, ESI) calc'd for C27H24ClF4N4O (M+H): 531.1. Found: 531.6.

Workup

  1. stirringto stir overnight
  2. customThe solvents were evaporated
  3. customchromatographed on silica gel eluting with MeOH/DCM (2.5, 5, and 10%)
  4. customto give a solid product
  5. stirringstirred for 5 minutes
  6. customthe solvents evaporated

Sources & evidence

ORD record
ord-ba0408b093734cb2a38147bf7a439501
Source dataset
uspto-grants-2005_05
Patent number
US06900231B2

Reaction notes

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