Formaldehyde → HCID 46913467, compound

HRID 1626553Notes

Reaction equation

HRID 1626553 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[CH3:28])[C:16]3[CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].C=O.[CH3:31]CN(CC)CC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[CH3:28])[C:16]3[CH2:21][N:20]([CH3:31])[CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 46913468HCID 46913468, compound

Product 1

HCID 46913467HCID 46913467, compoundYield 33.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea (example 7) (150 mg, 0.36 mmol) in THF (3 mL) was added aqueous formaldehyde 37 Wt % (58 μL, 0.72 mmol) and Et3N (149 μL, 1.07 mmol). The reaction mixture was then stirred at room temperature (20° C.) for 1 h. After this time sodium triacetoxyborohydride (152 mg, 0.72 mmol) was added and stirring at room temperature (20° C.) continued for 18 h. The crude reaction mixture was then partitioned between water and EtOAc, the phases separated and the organic layer washed with NaHCO3 and brine, dried over magnesium sulfate, filtered and the solvent removed in vacuo. The residue was purified by prep HPLC (low pH) to give as a light brown solid (48 mg, 33%).

Workup

  1. stirringstirring at room temperature (20° C.)
  2. waitcontinued for 18 h
  3. customThe crude reaction mixture
  4. customwas then partitioned between water and EtOAc
  5. customthe phases separated
  6. washthe organic layer washed with NaHCO3 and brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. customThe residue was purified by prep HPLC (low pH)

Sources & evidence

ORD record
ord-73105af73fa944afbbb4ad35b5bd4710
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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