Formaldehyde → HCID 67329641, compound

HRID 1846183Notes

Reaction equation

HRID 1846183 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH3:21])=[N:11][C:12](N)=[N:13][C:14]=1[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22]=O.[BH3-][C:25]#[N:26].[Na+]>CO>[CH2:1]([O:8][C:9]1[C:10]([CH3:21])=[N:11][C:12]([N:26]([CH3:25])[CH3:22])=[N:13][C:14]=1[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67329697HCID 67329697, compound

Product 1

HCID 67329641HCID 67329641, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution containing 334 mg (1.17 mmol) of 5-(benzyloxy)-4-methyl-6-pentylpyrimidin-2-amine in 4 mL of methanol were added 4 mL of 35% aq. formaldehyde followed by 588 mg (9.35 mmol) of NaCNBH3. The reaction mixture was stirred at 23° C. for 3 h. The reaction mixture was quenched with acetic acid until bubbling ceased then poured into 20 mL of water and extracted with two 40-mL portions of ethyl acetate. The combined organic layer was washed with one 40-mL portion of saturated aq. NaHCO3 and one 40-mL portion of brine. The organic solution was dried (MgSO4) and then concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (8×3 cm). Elution with 2:1 hexanes-ethyl acetate afforded the expected product as colorless oil: yield 150 mg (41%); silica gel TLC Rf 0.7 (2:1 hexanes-ethyl acetate); 1H NMR (CDCl3) δ 0.88 (t, 3H, J=7.2 Hz), 1.33 (m, 4H), 1.69 (quint, 2H, J=7.6 Hz), 2.32 (s, 3H), 2.62 (dd, 2H, J=8.0, 8.0 Hz), 3.15 (s, 6H), 4.70 (s, 2H) and 7.33-7.44 (m, 5H); 13C NMR (CDCl3) δ 14.00, 19.31, 22.54, 27.52, 31.67, 31.81, 37.22, 37.22, 75.73, 127.94, 128.13, 128.13, 128.55, 128.55, 137.15, 141.26, 158.60, 160.01 and 163.48; mass spectrum (APCI), m/z 314.2224 (M+H)1 (C19H28N3O requires 314.2232).

Workup

  1. customThe reaction mixture was quenched with acetic acid
  2. customuntil bubbling
  3. additionceased then poured into 20 mL of water
  4. extractionextracted with two 40-mL portions of ethyl acetate
  5. washThe combined organic layer was washed with one 40-mL portion of saturated aq. NaHCO3 and one 40-mL portion of brine
  6. dry with materialThe organic solution was dried (MgSO4)
  7. concentrationconcentrated under diminished pressure
  8. customThe residue was purified by chromatography on a silica gel column (8×3 cm)
  9. washElution with 2:1 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-3a9a4080b75f409da9866aa7d5d4ec46
Source dataset
uspto-grants-2015_02
Patent number
US08952025B2

Reaction notes

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