Diisopropylethylamine → HCID 45254395, compound

HRID 872394Notes

Reaction equation

HRID 872394 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH2:8][O:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([NH:20][C:21]([NH:23][C:24]2[N:28]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)[N:27]=[C:26]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH:25]=2)=[O:22])=[CH:12][CH:11]=1.CCN(C(C)C)C(C)C.[CH3:49][O:50][CH2:51][CH2:52][O:53][CH2:54][C:55](Cl)=[O:56]>C(Cl)Cl.CN(C=O)C>[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:7]3[CH:6]=[CH:5][N:4]=[CH:3][C:2]=3[NH:1][C:55](=[O:56])[CH2:54][O:53][CH2:52][CH2:51][O:50][CH3:49])=[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

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 70103382-(2-Methoxyethoxy)acetyl chlorideHCID 58416751HCID 58416751, compound2×

Product 1

HCID 45254395HCID 45254395, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(4-((3-aminopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate C) (50 mg, 0.10 mmol) and DIPEA (33.5 μl, 0.19 mmol) in anhydrous DCM (1.0 mL) and anhydrous DMF (0.2 mL) was added 2-(2-methoxyethoxy)acetyl chloride (15 μl, 0.11 mmol). The reaction mixture was stirred for 12 hr at RT. LC-MS indicated 50% conversion to the desired product. 2-(2-methoxyethoxy) acetyl chloride (15 μl, 0.11 mmol) was added and the reaction mixture stirred at RT. After 6 hr, LC-MS indicated the reaction had gone to completion. MeOH (2.0 mL) and AcOH (5 drops) were added and the reaction mixture was subjected to SCX capture and release, eluting with 1% NH3 in MeOH. The solvent was removed in vacuo and the crude material purified by column chromatography (4 g, 0-10% MeOH in EtOAc, gradient elution) to afford N-(4-((4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-3-yl)-2-(2-methoxyethoxy) acetamide (Example 17) as a white solid (27 mg, 43%): m/z 637 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9H, s), 2.39 (3H, s), 3.18 (3H, s), 3.36 (2H, m), 3.61 (2H, m), 4.14 (2H, s), 5.33 (2H, s), 6.35 (1H, s), 6.97 (1H, d), 7.35 (2H, d), 7.43 (2H, d), 7.67-7.55 (4H, m), 7.92 (1H, d), 8.27 (1H, d), 8.46 (1H, d), 8.58 (1H, s), 8.74 (1H, s), 8.80 (1H, s), 9.65 (1H, s).

Sources & evidence

ORD record
ord-9ee76fdef86c4f7a8b84c8fd45be5c68
Source dataset
uspto-grants-2015_03
Patent number
US08975285B2

Reaction notes

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