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 872400Notes

Reaction equation

HRID 872400 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 (9H, s), 2.37 (3H, s), 3.20 (2H, t), 3.37 (3H, s), 4.06 (2H, s), 4.38 (2H, t), 6.33 (1H, s), 6.95 (1H, d), 7.19 (1H, dd), 7.33 (2H, m), 7.42-7.47 (3H, m), 7.54 (1H, m), 7.59 (1H, d), 7.87 (1H, d), 8.12 (1H, d), 8.18 (1H, bs), 8.23 (1H, d), 8.67 (1H, s), 8.84 (1H, s), 9.89 (1H, 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-292c170917c94a23b267468bef555ab1
Source dataset
uspto-grants-2015_03
Patent number
US08975285B2

Reaction notes

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