Acetic Acid → HCID 10071952, compound

HRID 392164Notes

Reaction equation

HRID 392164 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]#[N:12])=[CH:8][CH:9]=2)[C:4]([CH2:13][CH2:14][CH2:15][NH:16][CH2:17][C@@H:18]2[O:32][C:22]3=[C:23]4[C:28](=[CH:29][CH:30]=[C:21]3[O:20][CH2:19]2)[N:27]=[C:26]([CH3:31])[CH:25]=[CH:24]4)=[CH:3]1.C=O.[C:35]([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]#[N:12])=[CH:8][CH:9]=2)[C:4]([CH2:13][CH2:14][CH2:15][N:16]([CH3:35])[CH2:17][CH:18]2[O:32][C:22]3=[C:23]4[C:28](=[CH:29][CH:30]=[C:21]3[O:20][CH2:19]2)[N:27]=[C:26]([CH3:31])[CH:25]=[CH:24]4)=[CH:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 131724603HCID 131724603, compound

Product 1

HCID 10071952HCID 10071952, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (2S)-1-methyl-3-{3-[(8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-2-ylmethyl)-amino]-proyl}-1H-indole-5-carbonitrile (0.1 g, 0.23 mmol) and formaldehyde (37 wt. % in water, 0.19 g, 2.3 mmol) in methanol (20 mL) was added sodium cyanoborohydride (0.026 g, 0.41 mmol) and acetic acid (0.027 mL, 0.46 mmol) at room temperature. The mixture was stirred at room temperature under nitrogen for 2 hours, then quenched with 1N NaOH (5 mL). The mixture was extracted with methylene chloride (3×50 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate, filtered and the solvent was removed under vacuum. The crude oil was column chromatographed on silica gel (5% methanol-ethyl acetate). The product-containing fractions were concentrated in vacuum to give 0.1 g of the (S)-enantiomer of the title compound as a brown oil. The dihydrochloride salt was prepared in ethyl acetate as a yellow solid (decomposed at 165° C.).

Workup

  1. customquenched with 1N NaOH (5 mL)
  2. extractionThe mixture was extracted with methylene chloride (3×50 mL)
  3. washThe organic layer was washed with water (3×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under vacuum
  7. customchromatographed on silica gel (5% methanol-ethyl acetate)
  8. concentrationThe product-containing fractions were concentrated in vacuum

Sources & evidence

ORD record
ord-03a196a796cd443ea12b6c191c2faa1f
Source dataset
uspto-grants-2004_10
Patent number
US06800637B2

Reaction notes

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