Methylamine → HCID 53810243, compound

HRID 966995Notes

Reaction equation

HRID 966995 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])([CH:14]=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O-]S([O-])(=O)=O.[Mg+2].CN.CC([O-])=O.[Na+].[BH3-][C:39]#[N:40].[Na+]>COCCOC.CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])([CH2:14][NH:40][CH3:39])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 54233415HCID 54233415, compound

Product 1

HCID 53810243HCID 53810243, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of the aldehyde of Example 198, Step A (340 mg, 1 mmol) in dry DME (10 mL) was added about 250 mg MgSO4 followed by methyl amine (1 mL of a 2.0 M solution in MeOH, 2 equiv). The reaction was monitored by MS for the consumption of aldehyde and formation of the corresponding imine (+APcI (M+1)+ 354). Once imine formation was complete, NaOAc (820 mg, 10 mmol) and NaCNBH3 (248 mg, 4 mmol) were added and the mixture was stirred at room temperature for 1 h. The mixture was filtered through Celite® and the filtrate was concentrated. The resulting residue was taken up in EtOAc (25 mL) and washed with 1 N NaOH and brine solutions, respectively. The organic phase was dried over MgSO4 and concentrated to deliver the crude amine (306 mg). Purification by flash chromatography (SiO2 gel, 3:1:0.2 EtOAc:Hexane:EtOH) delivered 210 mg (59%) of the diamine of Example 198, Step B: +APcI MS (M+1)+ 356, (M-tBu+1)+ 300, (M-Boc+1)+ 256; 1H NMR=400 MHz (CDCl3) δ: 7.21 (m, 1H), 6.81 (m, 2H), 2.51 (br s, 3H), 1.42 (s, 9H).

Workup

  1. customThe reaction was monitored by MS for the consumption of aldehyde and formation of the corresponding imine (+APcI (M+1)+ 354)
  2. filtrationThe mixture was filtered through Celite®
  3. concentrationthe filtrate was concentrated
  4. washwashed with 1 N NaOH and brine solutions
  5. dry with materialThe organic phase was dried over MgSO4
  6. concentrationconcentrated
  7. customPurification by flash chromatography (SiO2 gel, 3:1:0.2 EtOAc:Hexane:EtOH)

Sources & evidence

ORD record
ord-d75b30f9e0e342c68a693fff3f1593e8
Source dataset
uspto-grants-2005_10
Patent number
US06953791B2

Reaction notes

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