Formaldehyde → HCID 11741968, compound

HRID 1785394Notes

Reaction equation

HRID 1785394 reaction equation
N[CH2:2][C:3]([C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH2:28])[N:23]=3)=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[N:14]=[C:8]2[CH:7]=1)([CH3:5])[CH3:4].[CH3:29]O.C=O.[BH3-][C:34]#[N:35].[Na+]>C1COCC1.C(O)(=O)C>[CH3:29][N:35]([CH3:34])[CH2:2][C:3]([C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH2:28])[N:23]=3)=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[N:14]=[C:8]2[CH:7]=1)([CH3:5])[CH3:4]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 24887414HCID 24887414, compound

Product 1

HCID 11741968HCID 11741968, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 28 mL Pyrex-Plus tube containing amine 28 (Example 3, 170 mg, 0.452 mmol) was charged with methanol (2.0 mL), then acetic acid (170 □L), then formaldehyde (110 mg of a 37% aqueous solution, 1.35 mmol), then NaBH3CN (2.26 mL of a 1.0M solution in THF, 2.26 mmol). After stirring at room temperature for 1 hour, the reaction mixture was injected directly onto a 40 g Isco RediSep normal phase silica cartridge, and purified on an Isco OptiX10 CombiFlash instrument using a gradient that started at 100% methylene chloride and ended at 90% methylene chloride, 9% methanol, 1% concentrated arnmonium hydroxide. Fractions containing desired product were pooled and concentrated under reduced pressure, yielding 140 mg of dimethylamine 29. This sample was dissolved in 5 mL methanol and purified on an HPLC column, from 5×1.0 mL injections, using a gradient that started at 40% methanol and 60% water and ended at 100% methanol. Fractions containing desired product were pooled and concentrated under reduced pressure. Yield of 29: 104 mg (57%). 1H NMR (500 MHz, CDCl3) δ 1.39 (s, 6H), 2.15 (s, 6H), 2.54 (s, 2H), 5.11 (bs, 2H), 6.54 (d, J=5.5 Hz, 1H), 7.06 (dd, J=7.3, 2.0 Hz, 1H), 7.13 (m, 2H), 7.67 (m, 3H), 8.12 (d, J=5.5 Hz, 1H), 9.44 (dd, J=7.3, 0.5 Hz, 1H). MS (ESI+) 405.3.

Workup

  1. custompurified on an Isco OptiX10 CombiFlash instrument
  2. additionFractions containing desired product
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f394c6fe0aa74eea8704dbc923d9f2c6
Source dataset
uspto-grants-2009_03
Patent number
US07504501B2

Reaction notes

Loading…