Ammonia → Jnj-49095397

HRID 2067003Notes

Reaction equation

HRID 2067003 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:21]([NH:23][C:24]3[N:28]([C:29]4[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=4)[N:27]=[C:26]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH:25]=3)=[O:22])=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[CH3:49][O:50][CH2:51][C:52](Cl)=[O:53].N>CO.CN(C=O)C.C(Cl)Cl>[C:36]([C:26]1[CH:25]=[C:24]([NH:23][C:21](=[O:22])[NH:20][C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:10]([O:9][CH2:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:52](=[O:53])[CH2:51][O:50][CH3:49])[CH:7]=3)=[CH:11][CH:12]=2)[N:28]([C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)[N:27]=1)([CH3:39])([CH3:38])[CH3:37]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 81531Diisopropylethylamine2×HCID 96623Methoxyacetyl chloride2×HCID 584167531-(4-((2-Aminopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea

Product 1

HCID 45109868Jnj-49095397Yield 50.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-{4-[(2-aminopyridin-4-yl)methoxy]naphthalen-1-yl}-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (5) (526 mg, 0.96 mmol) and DIPEA (184 μL, 1.06 mmol) in mixture of DCM and DMF (10:1, 11 mL) was added methoxyacetyl chloride (92 μL, 1.01 mmol). After 1 h at RT further aliquots, of DIPEA (184 μL, 1.06 mmol) and methoxyacetyl chloride (92 μL, 1.01 mmol) were added sequentially and stirring was continued for 1 h. A solution of 1% ammonia in MeOH (40 mL), was added and the mixture stirred for 15 mins and then concentrated in vacuo. The crude product was purified by flash column chromatography (Biotage 40 g); eluting with 0 to 6% MeOH in DCM to furnish N-[4-({4-[3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido]naphthalen-1-yloxy}methyl)pyridin-2-yl]-2-methoxyacetamide (1) (286 mg, 49%): m/z 593 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9H, s), 2.39 (3H, s), 3.32 (3H, s), 4.08 (2H, s), 5.39 (2H, s), 6.36 (1H, s), 7.03 (1H, d), 7.28 (1H, dd), 7.36 (2H, m), 7.44 (2H, m), 7.56-7.64 (3H, m), 7.93 (1H, m), 8.30-8.35 (3H, m), 8.58 (1H, s), 8.79 (1H, s) and 10.02 (1H, s).

Workup

  1. waitwas continued for 1 h
  2. stirringthe mixture stirred for 15 mins
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash column chromatography (Biotage 40 g)
  5. washeluting with 0 to 6% MeOH in DCM

Sources & evidence

ORD record
ord-598f3b52969948509c22aee23b761101
Source dataset
uspto-grants-2012_10
Patent number
US08293771B2

Reaction notes

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