Formaldehyde → HCID 131730712, compound

HRID 450818Notes

Reaction equation

HRID 450818 reaction equation
N[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7](C1CCCCC1NS(C)(=O)=O)[CH:6](C1C=CC(Cl)=CC=1Cl)[CH:5]2[C:32]([NH:34][O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1)=[O:33].C=O.S(=O)(=O)(O)O.[BH4-].[Na+]>C1COCC1>[O:12]=[C:8]1[C:9]2[C:4](=[CH:3][CH:2]=[CH:11][CH:10]=2)[CH:5]([C:32]([NH:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)=[O:33])[CH2:6][NH:7]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 4311764Sodium borohydrideHCID 72303645HCID 72303645, compound

Product 1

HCID 131730712HCID 131730712, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 300 mg of (3RS,4RS)-6-amino-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-N-(pyridin-2-ylmethoxy)-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 213 mg of formaldehyde, and 11 mg of sulfuric acid in 5 ml of THF was added 125 mg of sodium borohydride at 0° C., followed by stirring for 2 hours. The reaction solution was poured into ice water and the organic layer was extracted with ethyl acetate. The solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by reverse-phase silica gel column chromatography (eluent: acetonitrile-water) to obtain 10 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-6-(dimethylamino)-2-(1R,2S)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-N-(pyridin-2-ylmethoxy)-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a yellow solid.

Workup

  1. extractionthe organic layer was extracted with ethyl acetate
  2. dry with materialThe solution was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by reverse-phase silica gel column chromatography (eluent: acetonitrile-water)

Sources & evidence

ORD record
ord-daec33a131a8499288a72d9fff487024
Source dataset
uspto-grants-2013_07
Patent number
US08486970B2

Reaction notes

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