Formaldehyde → HCID 10950087, compound

HRID 1243358Notes

Reaction equation

HRID 1243358 reaction equation
[CH2:1]([O:8][C:9]([CH2:11][N:12]1[C:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20](N)[CH:19]=2)=[C:16]([Cl:25])[N:15]=[C:14]([Cl:26])[C:13]1=[O:27])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]=O.[BH3-][C:31]#[N:32].[Na+]>C(#N)C.C(OCC)C.C(O)(=O)C.ClCCl>[CH2:1]([O:8][C:9]([CH2:11][N:12]1[C:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N:32]([CH3:31])[CH3:28])[CH:19]=2)=[C:16]([Cl:25])[N:15]=[C:14]([Cl:26])[C:13]1=[O:27])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 11784446HCID 11784446, compound

Product 1

HCID 10950087HCID 10950087, compoundYield 82%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolvent2×HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

The 1-benzyloxycarbonylmethyl-3,5-dichloro-6-(3-aminophenyl)-pyrazinone (210.6 mg, 0.48 mmol) was taken up in 9 mL of acetonitrile. Polyamine resin (1.05 g, 4.9 mmol) was added, along with about 10 mL of dichloromethane. After agitating about 10 mins the resin was filtered, rinsed with acetonitrile, and the solvents concentrated to about 10 mL. Formaldehyde (37%) (0.4 mL, 4.9 mmol) was added, followed by NaCNBH3 (1.0 M in THF, 1.5 mL, 1.5 mmol) and the dropwise addition of two 50 mL portions of glacial acetic acid (17.4 M, 1.74 mmol). The reaction was monitored by LC/MS. A third 50 mL portion of glacial acetic acid was added after 3.5 h to force the reaction to completion. The solution was diluted with about 40 mL of diethyl ether and washed with 1.2 M NaOH (3×5 mL), saturated NaCl (1×5 mL), dried over MgSO4, and the solvents were removed under reduced pressure to give 0.17 g (82% yield) of 1-benzyloxycarbonylmethyl-3,5-dichloro-6-(3-[N,N-dimethylamino]phenyl)pyrazinone (EX-103A): 1H NMR (300 MHz, CDCl3): δ 2.96 (s, 6H), 459 (s, 2H), 5.19 (s, 2H), 6.55 (m, 2H), 6.82 (d, 1H), 7.25–7.40 (m, 6H).

Workup

  1. filtrationwas filtered
  2. washrinsed with acetonitrile
  3. concentrationthe solvents concentrated to about 10 mL
  4. customthe reaction to completion
  5. washwashed with 1.2 M NaOH (3×5 mL), saturated NaCl (1×5 mL)
  6. dry with materialdried over MgSO4
  7. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-7d426f365ba14b9784066168e458c512
Source dataset
uspto-grants-2006_10
Patent number
US07119094B1

Reaction notes

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