Formaldehyde → HCID 59504625, compound

HRID 2400599Notes

Reaction equation

HRID 2400599 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[C:30](=[O:31])[CH2:29][NH:28][CH2:27]4)=[CH:22][CH:21]=3)[N:16]=2)[CH:3]=1.C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.ClCCl>[CH3:34][N:28]1[CH2:29][C:30](=[O:31])[N:26]([C:23]2[CH:24]=[CH:25][C:20]([C:17]3[N:16]=[C:15]([C:4]4[CH:3]=[C:2]([CH3:1])[N:6]([CH2:7][C:8]5[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=5)[N:5]=4)[O:19][N:18]=3)=[CH:21][CH:22]=2)[CH2:27]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59504651HCID 59504651, compound

Product 1

HCID 59504625HCID 59504625, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(4-{5-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazol-3-yl}-phenyl)imidazolidin-4-one (Example 141, 50 mg, 0.12 mmol) and aqueous formaldehyde solution (37%, 0.09 mL, 1.21 mmol) in acetic acid (0.5 mL) was stirred at rt for 15 min and then cooled to 0° C. Sodium triacetoxyborohydride (384 mg, 1.81 mmol) was added, and the mixture was stirred for 1 h at 0° C. and then at rt over night. Dichloromethane was added, and the mixture was extracted twice with saturated aqueous sodium bicarbonate solution, whereupon it was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to preparative HPLC (RP-18 column; acetonitrile/water gradient containing 0.1% trifluoroacetic acid). The product-containing fractions were combined, and the solvent was partly removed which resulted in precipitation of a solid. A neutral pH was established by adding saturated aqueous sodium bicarbonate solution, and the mixture was stirred for 30 min whereupon the solid was filtered off and dried under reduced pressure to yield the title compound (30 mg, 59%): 1H NMR (400 MHz, CDCl3) δ 8.22 (d, 2H), 7.69 (d, 2H), 7.12 (d, 2H), 7.08 (d, 2H), 6.80 (s, 1H), 5.41 (s, 2H), 4.61 (s, 2H), 3.48 (s, 2H), 2.58 (s, 3H), 2.33 (s, 3H), 2.27 (s, 3H); ES-MS m/z 429 (MH)+, HPLC RT (Method D) 2.31 min.

Workup

  1. temperaturecooled to 0° C
  2. stirringthe mixture was stirred for 1 h at 0° C.
  3. waitat rt over night
  4. extractionthe mixture was extracted twice with saturated aqueous sodium bicarbonate solution, whereupon it
  5. dry with materialwas dried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was subjected to preparative HPLC (RP-18 column; acetonitrile/water gradient containing 0.1% trifluoroacetic acid)
  8. customthe solvent was partly removed which
  9. customresulted in precipitation of a solid
  10. stirringthe mixture was stirred for 30 min whereupon the solid
  11. filtrationwas filtered off
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-26e6e470e5ab4caa914ea832b486e093
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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