Formaldehyde → 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-methylazetidin-3-amine

HRID 1717549Notes

Reaction equation

HRID 1717549 reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([C:9]([N:11]2[CH2:14][CH:13]([NH2:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].CO.C=O.[C:29]([BH3-])#N.[Na+]>O1CCCC1>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([C:9]([N:11]2[CH2:14][CH:13]([NH:15][CH3:29])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 162218891-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine

Product 1

HCID 162226051-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-methylazetidin-3-amineYield 35.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine (0.10 M in acetonitrile, 1.0 mL, 0.09 mmol), prepared using procedures similar to those described in Example 2, in 1:1 ratio of methanol and tetrahydrofuran (2.0 mL) was added formaldehyde (37% wt, 6.7 μL, 0.09 mmol) followed by sodium cyanoborohydride (11.0 mg, 0.18 mmol). The reaction mixture was stirred at room temperature for 16 h, at which time it was quenched with saturated aqueous ammonium chloride. The solution was then purified directly by reverse phase HPLC to afford the title compound (14.9 mg). 1H NMR (400 MHz, CDCl3): 8.13 (br s, 1H), 7.35 (d, 1H), 7.30 (d, 1H), 7.09-7.04 (m, 1H), 6.84-6.78 (m, 1H), 6.60-6.54 (m, 1H), 4.46-4.33 (br m, 4H), 3.93 (br m, 1H), 2.64 (s, 3H). MS (EI) for C17H15F3IN3O: 462 (MH+).

Workup

  1. customwas quenched with saturated aqueous ammonium chloride
  2. customThe solution was then purified directly by reverse phase HPLC

Sources & evidence

ORD record
ord-41405684c6f04ba5bffc8cf78f7d7462
Source dataset
uspto-grants-2010_09
Patent number
US07803839B2

Reaction notes

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