Oxalyl chloride → HCID 178480676, compound

HRID 16726

Reaction equation

C(Cl)(=O)C(Cl)=O.[CH3:7][N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1.CCN(C(C)C)C(C)C.[CH2:32]([C:40]1[CH:41]=[C:42]([NH2:45])[NH:43][N:44]=1)[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(Cl)Cl>[CH3:7][N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:45][C:42]3[NH:43][N:44]=[C:40]([CH2:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH:41]=3)=[O:20])=[CH:21][CH:22]=2)[CH2:12][CH2:13]1

Participants

Conditions

Temperature: 0 °C

Procedure

Oxalyl chloride (2M in DCM, 250 μl, 0.50 mmol, 1.1 eq) was added dropwise to a mixture of 4-(4-methylpiperazin-1-yl)benzoic acid (100 mg, 0.45 mmol, 1 eq) in DCM (5 ml, containing a few drops of DMF) and DIPEA (171 μl, 0.95 mmol, 2.1 eq) at O° C. After stirring for 1 h at 0° C., a solution of 5-phenethyl-2H-pyrazol-3-amine (128 mg, 0.68 mmol, 1.5 eq) in DCM (2 ml) was added dropwise. The mixture was maintained at 0° C. for 2 h, then gradually allowed to warm to room temperature overnight. The mixture was diluted with DCM (50 ml), washed with aq. NaHCO3 solution (50 ml) and the aqueous layer was extracted with DCM (50 ml). The combined organic layers were concentrated. The crude product was purified by reverse-phase prep. HPLC (basic) using a 30-50% gradient of acetonitrile in water (containing 1% ammonium hydroxide) to yield the title compound (8 mg, 3% yield).

Workup

temperatureThe mixture was maintained at 0° C. for 2 h
temperatureto warm to room temperature overnight
washwashed with aq. NaHCO3 solution (50 ml)
extractionthe aqueous layer was extracted with DCM (50 ml)
concentrationThe combined organic layers were concentrated
customThe crude product was purified by reverse-phase prep

Sources & evidence

ORD record: ord-497ee524cd6c46a081af0d4567cf7fca
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07737149B2

Linked notes

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