Ammonia → HCID 54589267, compound

HRID 571115Notes

Reaction equation

HRID 571115 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([S: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.CCN(C(C)C)C(C)C.[CH3:48][O:49][CH2:50][C:51](Cl)=[O:52].N>C(Cl)Cl>[C:35]([C:25]1[CH:24]=[C:23]([NH:22][C:20](=[O:21])[NH:19][C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:9]([S:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:51](=[O:52])[CH2:50][O:49][CH3:48])[CH:7]=3)=[CH:10][CH:11]=2)[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

6

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 67458743HCID 67458743, compound

Product 1

HCID 54589267HCID 54589267, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(4-(2-aminopyridin-4-ylthio)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (44 mg, 0.084 mmol) and DIPEA (52 μL, 0.30 mmol) in DCM (2.0 mL) was added a solution of 2-methoxyacetyl chloride (19 μL, 0.21 mmol) in DCM (0.5 mL) over 5 min. The reaction mixture was kept at RT for 30 min and a solution of NH3 (1% in MeOH, 1.0 mL) was added. The mixture was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, 12 g, EtOAc in isohexane, 30-80%, gradient elution) to afford the title compound, Example 21, as a white solid (36 mg, 70%). Rt 2.76 min (Method 2); m/z 595 (M+H)+ (ES+); 1H NMR (400 MHz, DMSO-d6) δ: 1.28 (9H, s), 2.39 (3H, s), 3.28 (3H, s), 3.95 (2H, s), 6.44 (1H, s), 6.56 (1H, dd), 7.37 (2H, d), 7.47 (2H, d), 7.65 (2H, m), 7.75 (1H, s), 7.93 (1H, d), 8.02 (1H, d), 8.17-8.23 (3H, overlapping m), 8.97 (1H, s), 9.37 (1H, s), 9.90 (1H, s).

Workup

  1. customThe mixture was evaporated in vacuo
  2. customthe residue was purified by flash column chromatography (SiO2, 12 g, EtOAc in isohexane, 30-80%, gradient elution)

Sources & evidence

ORD record
ord-76bcaa3fa96a46639897dfa0be503b0e
Source dataset
uspto-grants-2015_05
Patent number
US09024041B2

Reaction notes

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