Methanol → 4-tert-Butyl-6-morpholin-4-ylmethyl-pyridin-2-ylamine

HRID 1446714Notes

Reaction equation

HRID 1446714 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=O)[CH:5]=[C:4]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:3]=1.CO>C1COCC1>[C:16]([C:4]1[CH:5]=[C:6]([CH2:8][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[N:7]=[C:2]([NH2:1])[CH:3]=1)([CH3:19])([CH3:17])[CH3:18]

Participants

4

Reactant 2

HCID 887MethanolHCID 68542625(6-Amino-4-tert-butyl-pyridin-2-yl)-morpholin-4-yl-methanone

Product 1

HCID 685448704-tert-Butyl-6-morpholin-4-ylmethyl-pyridin-2-ylamineYield 35.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Suspend (6-amino-4-tert-butyl-pyridin-2-yl)-morpholin-4-yl-methanone (6.02 g, 22.86 mmol) in 40 mL anhydrous THF. Add 2 M solution of BH3-Me2S complex in THF (34.3 mL, 68.6 mmol, 3 eq) dropwise at room temperature. On BH3-Me2S/THF solution addition, the suspension turns clear and bright yellow after complete addition. Stir overnight at room temperature under nitrogen atmosphere. Carefully quench reaction with slow addition of MeOH (24 mL), stir 3 hours at 60° C. and concentrate in vacuo. Purify the residue on 300 g silica cartridge with a gradient of 0→2% MeOH in dichloromethane over 2 minutes, followed by 2→10% MeOH in dichloromethane over 40 minutes. Concentrate and dry clean fractions to give 2.0 g (35%) of the title compound as a white solid. LCMS (ES) m/z 250 (M+1).

Workup

  1. additionOn BH3-Me2S/THF solution addition
  2. additionbright yellow after complete addition
  3. customCarefully quench reaction
  4. stirringstir 3 hours at 60° C.
  5. concentrationconcentrate in vacuo
  6. customPurify the residue on 300 g silica cartridge with a gradient of 0→2% MeOH in dichloromethane over 2 minutes
  7. waitfollowed by 2→10% MeOH in dichloromethane over 40 minutes
  8. concentrationConcentrate
  9. customdry clean fractions

Sources & evidence

ORD record
ord-34a8fee83aa045beb577f01b23aa9411
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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