Formaldehyde → HCID 67448457, compound

HRID 1853873Notes

Reaction equation

HRID 1853873 reaction equation
N[CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8]/[CH:9]=[CH:10]/[C:11]2[C:12]3[C:13]4[CH:25]=[CH:24][S:23][C:14]=4[C:15](=[O:22])[NH:16][C:17]=3[CH:18]=[CH:19][C:20]=2[OH:21])[CH2:3]1.[CH2:26]=O.[C:28]([BH3-])#[N:29].[Na+]>CO>[CH3:26][N:29]([CH3:28])[CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8]/[CH:9]=[CH:10]/[C:11]2[C:12]3[C:13]4[CH:25]=[CH:24][S:23][C:14]=4[C:15](=[O:22])[NH:16][C:17]=3[CH:18]=[CH:19][C:20]=2[OH:21])[CH2:3]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67448225HCID 67448225, compound

Product 1

HCID 67448457HCID 67448457, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (E)-9-[3-(3-aminopiperidin-1-yl)prop-1-enyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (60 mg, 0.15 mmol) and formaldehyde (37% in water, 13 mg, 0.44 mmol) in methanol (1 mL) was stirred at room temperature for 30 min followed by the addition of sodium cyanoborohydride (28 mg, 0.44 mmol). The reaction mixture was stirred at room temperature overnight, concentrated and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with methylene chloride. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by preparatory HPLC (C18 silica, water/acetonitrile w/0.05% TFA gradient) to afford the desired product (30 mg, 53%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 7.97 (dd, J=19.4, 5.3 Hz, 2H), 7.30 (d, J=8.9 Hz, 1H), 7.23 (d, J=15.9 Hz, 1H), 7.07 (d, J=8.9 Hz, 1H), 6.33-6.22 (m, 1H), 4.32-4.18 (m, 3H), 3.90-3.77 (m, 2H), 3.47 (t, J=11.6 Hz, 1H), 3.18 (t, J=11.3 Hz, 1H), 3.01 (s, 6H), 2.40-2.23 (m, 2H), 2.10-1.84 (m, 2H).

Workup

  1. concentrationconcentrated
  2. custompartitioned between water and ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with methylene chloride
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparatory HPLC (C18 silica, water/acetonitrile

Sources & evidence

ORD record
ord-6d797b9416014fed9f4cfac3009dab82
Source dataset
uspto-grants-2015_02
Patent number
US08962648B2

Reaction notes

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