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Formaldehyde → Benzyl 2-[3-chloro-5-(3-[(dimethylamino)methyl]phenethylamino)-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate

HRID 567808
Notes
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Reaction equation

HRID 567808 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][NH:18][CH3:19])[CH:12]=2)[C:5](=[O:20])[N:4]([CH2:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[C:3]=1[CH3:32].C=O.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][N:18]([CH3:35])[CH3:19])[CH:12]=2)[C:5](=[O:20])[N:4]([CH2:21][C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[C:3]=1[CH3:32]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 18470865benzyl 2-[3-chloro-2-methyl-5-(3-[(methylamino)methyl]phenethylamino)-6-oxo-1(6H)-pyrazinyl]acetate

Product 1

HCID 18470815Benzyl 2-[3-chloro-5-(3-[(dimethylamino)methyl]phenethylamino)-2-methyl-6-oxo-1(6H)-pyrazinyl]acetateYield 77.1%

Reagents, catalysts & solvents 1

HCID 6344
Dichloromethane
Solvent
2×

Procedure

A stirred solution of benzyl 2-[3-chloro-2-methyl-5-(3 [(methylamino)methyl]phenethylamino)-6-oxo-1(6H)-pyrazinyl]acetate (preparation 19) (0.38 g, 0.83 mmol) in CH2Cl2 (10 ml) was treated with formaldehyde (0.31 ml). After stirring at room temperature for 45 mins, the resultant cloudy -mixture was treated with sodium triacetoxyborohydride (253 mg, 1.19 mmol) and stirred at room temperature for a further 2 days. The reaction mixture was diluted with CH2Cl2 (200 ml) and washed with sat. aq NaHCO3, sat aq brine and dried over MgSO4. Removal of the drying agent by filtration followed by evaporation of the solvent gave a crude solid which was purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 95:5 CH2Cl2:MeOH; 90:10 CH2Cl2:MeOH) to give the desired product (0.30 g, 77%). 1H NMR (CDCl3) δ 2.20 (s, 3H), 2.25 (s, 6H), 2.90 (t, 2H), 3.40 (s, 2H), 3.70 (m, 2H), 4.80 (s, 2H), 5.20 (s, 2H), 6.10 (m, br, 1H), 7.10-7.20 (m, 3H), 7.25 (m, 1H), 7.35 (m, 5H). LRMS m/z=469.2, 471.2 (M+1).

Workup

  1. stirringstirred at room temperature for a further 2 days
  2. washwashed with sat. aq NaHCO3
  3. dry with materialdried over MgSO4
  4. customRemoval of the drying agent
  5. filtrationby filtration
  6. customfollowed by evaporation of the solvent
  7. customgave a crude solid which
  8. customwas purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 95:5 CH2Cl2:MeOH; 90:10 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-3fe23796e008485cae5a2c7ecb6c5461
Source dataset
uspto-grants-2001_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06180627B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes