Diisopropylethylamine → HCID 45254766, compound

HRID 1916822Notes

Reaction equation

HRID 1916822 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][N:5]([CH2:7][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:6]=1.CCN(C(C)C)C(C)C.[CH3:49][O:50][CH2:51][C:52](Cl)=[O:53]>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][CH2:7][N:5]3[CH:6]=[C:2]([NH:1][C:52](=[O:53])[CH2:51][O:50][CH3:49])[N:3]=[CH:4]3)=[CH:11][CH:12]=2)[N:28]([C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)[N:27]=1)([CH3:39])([CH3:38])[CH3:37]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 584167591-(4-(2-(4-amino-1H-imidazol-1-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea2×

Product 1

HCID 45254766HCID 45254766, compoundYield 14.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1-(4-(2-(4-amino-1H-imidazol-1-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate I) (50 mg, 0.095 mmol) in DCM (2.0 mL) was added DIPEA (33 μl, 0.191 mmol) and 2-methoxyacetyl chloride (10 μl, 0.105 mmol). The mixture was stirred at RT overnight and then partitioned between saturated aq NaHCO3 solution (5.0 mL) and DCM (2.0 mL). The layers were separated through a phase separator cartridge and the organics were collected and evaporated under reduced pressure. The resulting residue was subjected to SCX capture and release and column chromatography (12 g), eluting with 0 to 10% MeOH in EtOAc. Trituration with EtOAc (5.0 mL) gave N-(1-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)ethyl)-1H-imidazol-4-yl)-2-methoxyacetamide (Example 24) as a white solid (8 mg, 14%): m/z 596 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.26 (9 H, s), 2.38 (3 H, s), 3.29 (3 H, s), 3.93 (2 H, s), 4.37 (2 H, t), 4.47 (2 H, t), 6.34 (1 H, s), 6.93 (1 H, d), 7.34 (2 H, m), 7.41-7.45 (3 H, m), 7.48-7.62 (4 H, m), 7.88 (1 H, d), 8.13-8.15 (1 H, dd), 8.54 (1 H, s), 8.75 (1 H, s), 9.84 (1 H, s).

Workup

  1. custompartitioned between saturated aq NaHCO3 solution (5.0 mL) and DCM (2.0 mL)
  2. customThe layers were separated through a phase separator cartridge
  3. customthe organics were collected
  4. customevaporated under reduced pressure
  5. washeluting with 0 to 10% MeOH in EtOAc

Sources & evidence

ORD record
ord-72f929f8d04e46b0b424f6cab525090f
Source dataset
uspto-grants-2013_12
Patent number
US08618140B2

Reaction notes

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