Dimethylformamide → HCID 46209239, compound

HRID 1020364Notes

Reaction equation

HRID 1020364 reaction equation
C1(C2C[CH2:11][N:10]([C:13]3[N:18]=[CH:17][C:16]([NH:19][C:20]([C:22]4[O:26][C:25]([N:27]5[C:36]6[C:31](=[CH:32]C=CC=6)[CH2:30][CH2:29][CH2:28]5)=[N:24][C:23]=4[C:37]([F:40])([F:39])[F:38])=[O:21])=[CH:15][CH:14]=3)[CH2:9]C2)C=CC=CC=1.Cl.CN(C)CCCN=C=NCC.ON1[C:58]2[CH:59]=[CH:60][CH:61]=[CH:62][C:57]=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:72][N:73]([CH:75]=[O:76])[CH3:74]>O>[O:76]=[C:75]1[N:73]([CH2:74][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH2:72][CH2:11][N:10]([C:13]2[N:18]=[CH:17][C:16]([NH:19][C:20]([C:22]3[O:26][C:25]([N:27]4[CH2:28][CH2:29][CH2:30][CH:31]([CH3:32])[CH2:36]4)=[N:24][C:23]=3[C:37]([F:39])([F:40])[F:38])=[O:21])=[CH:15][CH:14]=2)[CH2:9]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67390403HCID 67390403, compound

Product 1

HCID 46209239HCID 46209239, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of intermediate B-15 (170 mg, 0.6 mmol) and intermediate A-10 (185 mg, 0.67 mmol) in DMF (8 mL) were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (173 mg, 0.9 mmol, EDCI), 1-hydroxybenzotriazole (122 mg, 0.9 mmol, HOBT), and N,N-diisopropylethylamine (200 μL, 1.2 mmol). The reaction mixture was stirred at RT for 17 h. The mixture was poured into water (150 mL). The precipitate was filtered, dissolved in DMF and purified by chromatography on a C-18 reverse phase column (eluant: acetonitrile/water gradient) to give 2-(3-methyl-1-piperidinyl)-N-[6-[3-oxo-4-(phenylmethyl)-1-piperazinyl]-3-pyridinyl]-4-(trifluoromethyl)-5-oxazolecarboxamide (31) (169 mg, 52% yield) 1H NMR (500 MHz, CDCl3) δ 8.28 (s, 1H), 8.04 (d, 1H, J=9 Hz), 7.61 (s, 1H), 7.4-7.3 (m, 5H), 6.64 (d, 1H, J=9 Hz), 4.73 (s, 2H), 4.23 (s, 2H), 4.15 (bt, 2H), 3.88 (t, 2H, J=5.5 Hz), 3.43 (t, 2H, J=5.5 Hz), 3.08 (dt, 1H), 2.75 (t, 1H, J=12 Hz), 1.97-1.74 (m, 3H), 1.31 (bs, 1H), 1.28-1.16 (m, 2H), 1.03 (d, 3H, J=6.5 Hz). LCMS (ESI) Rt=3.83 min, 543.3 [M+1]+.

Workup

  1. filtrationThe precipitate was filtered
  2. dissolutiondissolved in DMF
  3. custompurified by chromatography on a C-18 reverse phase column (eluant: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-fe2b48f08bd54cc4b8801b9712bbbe10
Source dataset
uspto-grants-2014_05
Patent number
US08716312B2

Reaction notes

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