Formaldehyde → 6-[4-(1,3-benzoxazol-2-yl)-2-methoxyphenyl]-N,N-dimethylpyridin-3-amine

HRID 7794Notes

Reaction equation

HRID 7794 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:21]=[CH:20][C:19](N)=[CH:18][CH:17]=2)=[C:12]([O:23][CH3:24])[CH:11]=1.[BH3-][C:26]#[N:27].[Na+].[CH2:29]=O>CO.CC(O)=O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:21]=[CH:20][C:19]([N:27]([CH3:26])[CH3:29])=[CH:18][CH:17]=2)=[C:12]([O:23][CH3:24])[CH:11]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 101497166-[4-(1,3-Benzoxazol-2-yl)-2-methoxyphenyl]pyridin-3-amine

Product 1

HCID 102369126-[4-(1,3-benzoxazol-2-yl)-2-methoxyphenyl]-N,N-dimethylpyridin-3-amine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

6-[4-(1,3-benzoxazol-2-yl)-2-methoxyphenyl]pyridin-3-amine (22 mg, 0.070 mmol) was dissolved in MeOH (2 mL), and AcOH (2 drops). NaCNBH3 (44 mg, 0.70 mmol) and formaldehyde (50 μL, 0.70 mmol) were added and the mixture was stirred overnight. The mixture was partitioned between CH2Cl2 and dilute brine. The aqueous layer was extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude mixture was adsorbed onto silica gel and purified by automated flash chromatography using an EtOAc/hexanes gradient to afford the desired 6-[4-(1,3-benzoxazol-2-yl)-2-methoxyphenyl]-N,N-dimethylpyridin-3-amine: 1H NMR (CDCl3, 300 MHz) δ 8.24–8.23 (d, 1H), 7.94 (s, 2H), 7.87 (s, 1H), 7.84–7.79 (m, 2H), 7.59 (m, 1H), 7.38–7.35 (m, 2H), 7.07–7.06 (m, 1H), 4.01 (s, 3H), 3.04 (s, 6H). MS (ESI) 346 (M+H)+.

Workup

  1. customThe mixture was partitioned between CH2Cl2 and dilute brine
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×15 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by automated flash chromatography

Sources & evidence

ORD record
ord-5a63f83402bd4a00a7cdbe18b772ccfe
Source dataset
uspto-grants-2006_08
Patent number
US07087601B2

Reaction notes

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