Dimethylformamide → HCID 54589302, compound

HRID 571117Notes

Reaction equation

HRID 571117 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([NH:19][C:20]([NH:22][C:23]3[N:27]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)[N:26]=[C:25]([C:35]([CH3:38])([CH3:37])[CH3:36])[CH:24]=3)=[O:21])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH2:39]([N:41]=[C:42]=[O:43])[CH3:40].CN(C=O)C>C(Cl)Cl>[C:35]([C:25]1[CH:24]=[C:23]([NH:22][C:20]([NH:19][C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:9]([CH2:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:42]([NH:41][CH2:39][CH3:40])=[O:43])[CH:7]=3)=[CH:10][CH:11]=2)=[O:21])[N:27]([C:28]2[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=2)[N:26]=1)([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 8022Ethyl isocyanate2×HCID 67461998HCID 67461998, compound

Product 1

HCID 54589302HCID 54589302, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-((2-aminopyridin-4-yl)methyl)naphthalen-1-yl)-3-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)urea (55 mg, 0.11 mmol) in dry DCM (4.0 mL) under N2 at 0° C. was added ethyl isocyanate (22 μL, 0.27 mmol). The reaction mixture was maintained at 0° C. for 20 min, was then warmed to RT for 2 hr and dry DMF (200 μL) was added. Additional aliquots of ethyl isocyanate were added after 3.5 hr (22 μL, 0.27 mmol), after 21 hr (43 μL, 0.54 mmol) and after 28 hr (65 μL, 0.81 mmol). After 43 hr the reaction was quenched by the addition of a solution of NH3 (1% in MeOH, 3.0 mL) and after 45 min the resulting mixture was evaporated in vacuo. The residue was subjected to SCX capture and release and the crude product so obtained was purified by flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-80%, gradient elution) to afford the title compound, Example 23, as a white solid (26 mg, 40%); Rt 2.22 min (Method 2); m/z 576 (M+H)+ (ES+); 1H NMR (400 MHz, DMSO-d6) δ: 1.04 (3H, t), 1.28 (9H, s), 2.39 (3H, s), 3.14 (2H, m), 4.33 (2H, s), 6.40 (1H, s), 6.76 (1H, dd), 7.16 (1H, s), 7.36 (2H, d), 7.39 (1H, d), 7.45 (2H, d), 7.53 (2H, m), 7.87 (1H, d), 7.92 (1H, d), 8.01-8.04 (2H, overlapping m), 8.15 (1H, br t), 8.78 (1H, s), 9.04 (1H, s), 9.07 (1H, s).

Workup

  1. temperaturewas then warmed to RT for 2 hr
  2. waitafter 28 hr (65 μL, 0.81 mmol)
  3. customAfter 43 hr the reaction was quenched by the addition of a solution of NH3 (1% in MeOH, 3.0 mL) and after 45 min the resulting mixture
  4. customwas evaporated in vacuo
  5. customthe crude product so obtained
  6. customwas purified by flash column chromatography (SiO2, 12 g, [5% MeOH in EtOAc] in isohexane, 0-80%, gradient elution)

Sources & evidence

ORD record
ord-617f30de574a45c89b8f0f76b8176a99
Source dataset
uspto-grants-2015_05
Patent number
US09024041B2

Reaction notes

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