Formaldehyde → HCID 10278717, compound

HRID 2211675Notes

Reaction equation

HRID 2211675 reaction equation
[CH3:1][C:2]1([CH3:36])[C:10]2[C:5](=[CH:6][C:7]([NH:11][C:12](=[O:28])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][C:14]=3[NH:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[CH:8][CH:9]=2)[N:4]([CH2:29][CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH2:3]1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:41](C)=O.[Na+]>ClCCCl>[CH3:1][C:2]1([CH3:36])[C:10]2[C:5](=[CH:6][C:7]([NH:11][C:12](=[O:28])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][C:14]=3[NH:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[CH:8][CH:9]=2)[N:4]([CH2:29][CH:30]2[CH2:31][CH2:32][N:33]([CH3:41])[CH2:34][CH2:35]2)[CH2:3]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 21961418HCID 21961418, compound

Product 1

HCID 10278717HCID 10278717, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To N-(3,3-dimethyl-1-piperidin-4-ylmethyl-2,3-dihydro-1H-indol-6-yl)-2-(4-fluoro-benzylamino)-nicotinamide (0.92 g) dissolved in DCE (20 mL) at RT was added formaldehyde (37% aqueous, 0.42 mL) followed by NaBH(OAc)3 (1.59 g). After 4 h, the mixture was quenched with 1 N HCl (20 mL) and H2O (20 mL). It was basified with sat NaHCO3, extracted with CH2Cl2 (3×50 mL) and the combined extracts were washed with brine, dried (K2CO3) and concentrated onto SiO2 (previously treated with 10% MeOH (2 M NH3 in MeOH/CH2Cl2 and then concentrated in vacuo). The residue was purified by flash chromatography (Isco, 35 g column, 1-7% MeOH (2M NH3 in MeOH/CH2Cl2). The bulk of the crude yellow material was further purified by reverse phase Prep HPLC. The isolated fractions were partially concentrated and basified with 1 N NaOH and dried under vacuum to afford a slightly yellow powder. M+H=502.3. Calc'd for C30H36FN5O: 501.29.

Workup

  1. customthe mixture was quenched with 1 N HCl (20 mL) and H2O (20 mL)
  2. extractionextracted with CH2Cl2 (3×50 mL)
  3. washthe combined extracts were washed with brine
  4. dry with materialdried (K2CO3)
  5. concentrationconcentrated onto SiO2 (
  6. additionpreviously treated with 10% MeOH (2 M NH3 in MeOH/CH2Cl2
  7. concentrationconcentrated in vacuo)
  8. customThe residue was purified by flash chromatography (Isco, 35 g column, 1-7% MeOH (2M NH3 in MeOH/CH2Cl2)
  9. customThe bulk of the crude yellow material was further purified by reverse phase Prep HPLC
  10. concentrationThe isolated fractions were partially concentrated
  11. customdried under vacuum
  12. customto afford a slightly yellow powder

Sources & evidence

ORD record
ord-40af6158ad984a97a04b4a9fa95c3d2c
Source dataset
uspto-grants-2006_09
Patent number
US07101868B2

Reaction notes

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