Diisopropylethylamine → N-(4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)ethyl)pyridin-2-yl)-2-methoxyacetamide

HRID 1916799Notes

Reaction equation

HRID 1916799 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([NH:21][C:22]([NH:24][C:25]3[N:29]([C:30]4[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=4)[N:28]=[C:27]([C:37]([CH3:40])([CH3:39])[CH3:38])[CH:26]=3)=[O:23])=[CH:13][CH:12]=2)[CH:5]=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[CH3:50][O:51][CH2:52][C:53](Cl)=[O:54]>C(Cl)Cl.C([O-])(O)=O.[Na+]>[C:37]([C:27]1[CH:26]=[C:25]([NH:24][C:22](=[O:23])[NH:21][C:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:11]([O:10][CH2:9][CH2:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:53](=[O:54])[CH2:52][O:51][CH3:50])[CH:7]=3)=[CH:12][CH:13]=2)[N:29]([C:30]2[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=2)[N:28]=1)([CH3:40])([CH3:39])[CH3:38]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 584167451-(4-(2-(2-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea2×

Product 1

HCID 45254575N-(4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)ethyl)pyridin-2-yl)-2-methoxyacetamideYield 13%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of 1-(4-(2-(2-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate D) (35 mg, 0.065 mmol) in DCM (0.5 mL) was added DIPEA (23 μl, 0.131 mmol) and methoxyacetyl chloride (7 μl, 0.072 mmol). The mixture was stirred at RT, until judged to be complete by LC-MS; diluted with saturated aq NaHCO3 (1.5 mL) and the layers were separated through a phase separator cartridge. The organics were collected, evaporated under reduced pressure and the residue subjected to SCX capture and release. The resulting residue was purified further by preparative RP HPLC to give N-(4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)ethyl)pyridin-2-yl)-2-methoxyacetamide (Example 18) as a white solid (5 mg, 13%): m/z 607 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.26 (9 H, s), 2.37 (3 H, s), 3.20 (2 H, t), 3.37 (3 H, s), 4.06 (2 H, s), 4.38 (2 H, t), 6.33 (1 H, s), 6.95 (1 H, d), 7.19 (1 H, dd), 7.33 (2 H, m), 7.42-7.47 (3 H, m), 7.54 (1 H, m), 7.59 (1 H, d), 7.87 (1 H, d), 8.12 (1 H, d), 8.18 (1 H, bs), 8.23 (1 H, d), 8.67 (1 H, s), 8.84 (1 H, s), 9.89 (1 H, s).

Workup

  1. customthe layers were separated through a phase separator cartridge
  2. customThe organics were collected
  3. customevaporated under reduced pressure
  4. customThe resulting residue was purified further by preparative RP HPLC

Sources & evidence

ORD record
ord-e8aa909d3b0a48e79df72cdabff2d87e
Source dataset
uspto-grants-2013_12
Patent number
US08618140B2

Reaction notes

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