Diisopropylethylamine → 2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)-4-nitrobenzamide

HRID 914256Notes

Reaction equation

HRID 914256 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:16][N:17]1[CH2:22][CH2:21][CH:20]([NH2:23])[CH2:19][CH2:18]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4]([NH:23][CH:20]1[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]1)=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579556142-Fluoro-5-methoxy-4-nitrobenzoic acid

Product 1

HCID 671177462-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)-4-nitrobenzamideYield 70.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-fluoro-5-methoxy-4-nitrobenzoic acid (53.8 g, 250 mmol), 1-methylpiperidin-4-amine (31.4 g, 275 mmol), DIEA (134 mL, 750 mmol) in 1 L of DCM at 0° C. was added HATU (114 g, 300 mmol) in four batches. The reaction mixture was stirred at room temp. for 16 h. After which, it was concentrated and diluted to IL of a mixture of MeOH in water (5%). The suspension was stirred vigorously for 2 h until seen a suspension of fine powder. The solid was filtered, washed with more water and dried to give 55 g of light yellow product. The filtrate was extracted with EtOAc, concentrated and re-suspended in water (5% of MeOH) and repeating the same procedure as above, after which another batch of solid was obtained (total 67 g, 86%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.53 (m, 2H) 1.81 (m, 2H) 2.04 (m, 2H) 2.19 (s, 3H) 2.77 (d, J=8 Hz, 2H) 3.73 (m, 1H) 3.94 (s, 3H) 7.42 (d, J=5.6 Hz, 1H) 7.98 (d, J=8.8 Hz, 1H) 8.51 (d, J=7.6 Hz, 1H). [M+H] calc'd for C14H18FN3O4, 312. found 312.

Workup

  1. concentrationAfter which, it was concentrated
  2. additiondiluted to IL of a mixture of MeOH in water (5%)
  3. stirringThe suspension was stirred vigorously for 2 h
  4. additiona suspension of fine powder
  5. filtrationThe solid was filtered
  6. washwashed with more water
  7. customdried

Sources & evidence

ORD record
ord-461531e6a8534a6b8f047679a5c23af9
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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