Formaldehyde → HCID 10339487, compound

HRID 1785392Notes

Reaction equation

HRID 1785392 reaction equation
N[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][N:7]2[C:10]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH2:26])[N:21]=3)=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[N:12]=[C:6]2[CH:5]=1.[CH2:27]=O.[BH3-][C:30]#[N:31].[Na+]>C1COCC1.C(O)(=O)C.CO>[CH3:27][N:31]([CH3:30])[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][N:7]2[C:10]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH2:26])[N:21]=3)=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[N:12]=[C:6]2[CH:5]=1

Participants

7

Reactant 3

HCID 712Formaldehyde2×HCID 5003444Sodium cyanoborohydride2×HCID 57595185HCID 57595185, compound2×

Product 1

HCID 10339487HCID 10339487, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A 28 mL Pyrex-Plus tube containing the product of Example 1, Step 9 (30 mg, 0.086 mmol) was charged with methanol (1.0 mL), then acetic acid (33 □L), then formaldehyde (28 mg of a 37% aqueous solution, 0.34 mmol), then NaBH3CN (431 □L of a 1.0M solution in THF, 0.431 mmol), and stirred at room temperature for 12 hours. A separate 28 mL Pyrex-Plus tube containing the product of Example 1, Step 9 (70 mg, 0.20 mmol) was charged with methanol (2.0 mL), then acetic acid (67 □L), then formaldehyde (65 mg of a 37% aqueous solution, 0.80 mmol), then NaBH3CN (1.00 mL of a 1.0M solution in THF, 1.00 mmol), and stirred at room temperature for 2 hours. Both reaction mixtures were then combined, along with 50 mgs of crude product prepared previously then concentrated under reduced pressure, then dissolved in a minimum volume of methylene chloride, then 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 ammonium hydroxide. Fractions containing desired product were pooled and concentrated under reduced pressure, yielding 110 mg of dimethylamine 25. This sample was dissolved in 4 mL methanol and purified on an HPLC column, from 4×1.0 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. Quantity isolated of 25: 68 mg. 1H NMR (500 MHz, CDCl3) δ 2.33 (s, 6H), 2.64 (t, J=7.8 Hz, 2H), 2.89 (t, J=7.8 Hz, 2H), 5.11 (bs, 2H), 6.52 (d, J=5.5 Hz, 1H), 6.83 (dd, J=7.0, 2.0 Hz, 1H), 7.14 (m, 2H), 7.52 (dd, J=1.8, 0.5 Hz, 1H), 7.65 (m, 2H), 8.12 (d, J=5.5 Hz, 1H), 9.44 (dd, J=7.5, 0.5 Hz, 1H). MS (ESI+) 377.4.

Workup

  1. customBoth reaction mixtures
  2. customprepared previously
  3. concentrationthen concentrated under reduced pressure
  4. dissolutiondissolved in a minimum volume of methylene chloride
  5. custompurified on an Isco OptiX10 CombiFlash instrument
  6. additionFractions containing desired product
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0e54cd889301404c9d9d917959710da3
Source dataset
uspto-grants-2009_03
Patent number
US07504501B2

Reaction notes

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