Methylamine → HCID 53810243, compound

HRID 351471Notes

Reaction equation

HRID 351471 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 2.0M solution in MeOH, 2 equiv). The reaction was monitored by MS for the consumption of aldehyde and formation of the corresponding imine (+APcl(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 1N NaOH and brine solutions, respectively. The organic phase was dried over MgSO4 and concentrated to deliver the crude amine (360 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: +APcl 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, 3 H), 1.42 (s, 9H).

Workup

  1. customThe reaction was monitored by MS for the consumption of aldehyde and formation of the corresponding imine (+APcl(M+1)+ 354)
  2. filtrationThe mixture was filtered through Celite®
  3. concentrationthe filtrate was concentrated
  4. washwashed with 1N 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-386345944eaf42468598960b9233b868
Source dataset
uspto-grants-2004_06
Patent number
USRE038524E1

Reaction notes

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