Formaldehyde → HCID 58975535, compound

HRID 1178777Notes

Reaction equation

HRID 1178777 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([NH:11][CH2:12][CH2:13][NH:14][CH2:15][C:16]2[CH:17]=[C:18]([C:22]([N:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[O:23])[CH:19]=[CH:20][CH:21]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:2].C=O.[C:32]([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>CC#N.C(O)(=O)C.CCOC(C)=O.O>[CH:1]([O:4][C:5]1[CH:6]=[C:7]([NH:11][CH2:12][CH2:13][N:14]([CH2:15][C:16]2[CH:17]=[C:18]([C:22]([N:24]3[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]3)=[O:23])[CH:19]=[CH:20][CH:21]=2)[CH3:32])[CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 58975544HCID 58975544, compound

Product 1

HCID 58975535HCID 58975535, compoundYield 15.4%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (3-{[2-(3-isopropoxy-phenylamino)-ethylamino]-methyl}-phenyl)-piperidin-1-yl-methanone (Example 10; 0.048 g, 0.12 mmol) in CH3CN (10 mL) was added a solution of formaldehyde (0.0029 g, 0.097 mmol) in CH3CN (5 mL), followed by sodium cyanoborohydride (0.006 g, 0.1 mmol) and acetic acid (2 drops), and the resulting solution was stirred at 25° C. for 15 h. The solution was treated with aqueous satd NaHCO3 (20 mL), H2O (20 mL) and EtOAc (30 mL). The aqueous layer was back-extracted with EtOAc (3×40 mL), and the combined organic layers were washed with brine (40 mL), dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The crude residue was purified by preparative TLC (5% CH3OH/CH2Cl2) to provide a tan oil (0.0063 g, 13%). MS (ESI): mass calculated for C25H35N3O2, 409.27. m/z found, 410.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.39-7.26 (m, 4H), 7.04 (t, J=8.0 Hz, 1H), 6.26-6.16 (m, 3H), 4.15 (hept, J=6.0 Hz, 1H), 3.71-3.61 (m, 4H), 3.31-3.20 (m, 4H), 2.72 (br s, 2H), 2.26 (br s, 2H), 1.66-1.50 (m, 8H), 1.32 (d, J=6.0 Hz, 6H).

Workup

  1. extractionThe aqueous layer was back-extracted with EtOAc (3×40 mL)
  2. washthe combined organic layers were washed with brine (40 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe crude residue was purified by preparative TLC (5% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-44ca697fab2c407b9209bbc28fe5a7a7
Source dataset
uspto-grants-2007_10
Patent number
US07276610B2

Reaction notes

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