Chloroacetyl chloride → HCID 58416746, compound

HRID 1916781Notes

Reaction equation

HRID 1916781 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][C:11]1[CH:16]=[C:15]([CH2:17][O:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]([NH:29][C:30]([NH:32][C:33]3[N:37]([C:38]4[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=4)[N:36]=[C:35]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:34]=3)=[O:31])=[CH:21][CH:20]=2)[CH:14]=[CH:13][N:12]=1.[Cl:49][CH2:50][C:51](Cl)=[O:52]>C(Cl)Cl.CN(C=O)C>[C:45]([C:35]1[CH:34]=[C:33]([NH:32][C:30](=[O:31])[NH:29][C:22]2[C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:19]([O:18][CH2:17][C:15]3[CH:14]=[CH:13][N:12]=[C:11]([NH:10][C:51](=[O:52])[CH2:50][Cl:49])[CH:16]=3)=[CH:20][CH:21]=2)[N:37]([C:38]2[CH:39]=[CH:40][C:41]([CH3:44])=[CH:42][CH:43]=2)[N:36]=1)([CH3:48])([CH3:47])[CH3:46]

Participants

6

Reactant 3

HCID 6577Chloroacetyl chloride2×HCID 81531DiisopropylethylamineHCID 584167531-(4-((2-Aminopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea2×

Product 1

HCID 58416746HCID 58416746, compoundYield 46.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of DIPEA (1.37 ml, 7.68 mmol) and 1-(4-((2-aminopyridin-4-yl)methoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate A) (2.00 g, 3.84 mmol) in DCM (40 mL) and DMF (8.0 mL) was added chloroacetyl chloride (0.61 mL, 7.68 mmol). The reaction mixture was stirred at RT for 1 hr. LC-MS indicated nearly complete consumption of the starting material. A further portion of chloracetyl chloride (100 μl, 1.25 mmol) was added. After stirring for 1 hr at RT, the reaction mixture was partitioned between DCM (40 mL) and saturated aq NaHCO3 solution (40 mL). The organic phase was concentrated in vacuo and purified by column chromatography (80 g, 0-10% MeOH in DCM, gradient elution). Product fractions were concentrated in vacuo and the residue triturated with diethyl ether (20 mL) and iso-hexane (20 mL). The solid was collected by filtration to afford N-(4-((4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-2-yl)-2-chloroacetamide (Intermediate B) as a light purple solid (1.07 g, 42%): m/z 597, 599 (M+H)+ (ES+).

Workup

  1. customconsumption of the starting material
  2. stirringAfter stirring for 1 hr at RT
  3. customthe reaction mixture was partitioned between DCM (40 mL) and saturated aq NaHCO3 solution (40 mL)
  4. concentrationThe organic phase was concentrated in vacuo
  5. custompurified by column chromatography (80 g, 0-10% MeOH in DCM, gradient elution)
  6. concentrationProduct fractions were concentrated in vacuo
  7. customthe residue triturated with diethyl ether (20 mL) and iso-hexane (20 mL)
  8. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-1a9dcd293e55473998fda7f4f664aa7a
Source dataset
uspto-grants-2013_12
Patent number
US08618140B2

Reaction notes

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