N,N-Diphenylhydrazine → 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid N',N'-diphenyl-hydrazide

HRID 2382074Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:18]1([N:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH2:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>CN(C=O)C.CCOC(C)=O>[C:18]1([N:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:25][C:15]([C:11]2[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)=[O:17])[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (500 mg, 2.2 mmol) and N,N-diphenyl-hydrazine (422 mg, 2.2 mmol) in DMF (3 mL) is stirred at 50° C. for 15 min. The mixture is treated with DMTMM (633 mg, 2.2 mmol) and stirred at 50° C. for 3 h. The mixture is diluted with EtOAc (50 mL), and washed with saturated aqueous Na2CO3 (50 mL). The organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 75% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid N′,N′-diphenyl-hydrazide (60 mg, 7%). MS: 399 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.04 (s, 1H), 8.30 (d, 1H), 8.15 (m, 1H), 7.61 (m, 1H), 7.44 (m, 1H), 7.35 (m, 4H), 7.22 (m, 4H), 7.04 (m, 2H), 2.64 (s, 3H). IC50=16 nM.

Workup

washwashed with saturated aqueous Na2CO3 (50 mL)
customThe organic layer is separated
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue is purified by silica gel chromatography
washeluting with 75% EtOAc in heptane

Sources & evidence

ORD record: ord-1875ba4f3a9a472d86868f727a4dee91
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258130B2

Reaction notes

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