Morpholine → HCID 21099468, compound

HRID 2376948Notes

Reaction equation

HRID 2376948 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[CH:9]=[CH:10]/[C:11]1[N:16]=[CH:15][C:14]([S:17]([C:20]2[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=2)[CH:23]=O)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.C([BH3-])#N.[Na+].[OH-].[Na+]>CO.C(O)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[CH:9]=[CH:10]/[C:11]1[CH:12]=[CH:13][C:14]([S:17]([C:20]2[CH:27]=[CH:26][CH:25]=[C:22]([CH2:23][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:21]=2)(=[O:19])=[O:18])=[CH:15][N:16]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 21099491HCID 21099491, compound

Product 1

HCID 21099468HCID 21099468, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

3-({6-[(E)-2-(2,4-Difluorophenyl)vinyl]pyridin-3-yl}sulfonyl)benzaldehyde (Step 1, 95 mg, 0.25 mmol) was suspended in methanol (1 mL) and acetic acid (70 μL). Morpholine (28 μL, 0.34 mmol) was added and the reaction stirred at room temperature under nitrogen for 30 minutes. Sodium cyanoborohydride (15 mg, 0.25 mmol) was added and stirring continued for 2 days. 5N sodium hydroxide was added and the products extracted into dichloromethane, washed with brine, dried over MgSO4 and concentrated in vacuo. Purification by flash column chromatography (90% ethyl acetate/isohexane) gave the title compound as a yellow foam which was treated with ethereal HCl to give the hydrochloride salt (8 mg, 7%). δH (500 MHz, d6 DMSO): 11.24 (1H, s), 9.11 (1H, d, J=2.1 Hz), 8.38 (1H, dd, J=2.1, 8.2 Hz), 8.33 (1H, s), 8.08 (1H, d, J=7.8 Hz), 7.93 (2H, q, J=8.0 Hz), 7.87 (1H, d, J=16.1 Hz), 7.76-7.70 (2H, m), 7.46 (1H, d, J=16.1 Hz), 7.37-7.31 (1H, m), 7.18 (1H, td, J=2.1, 8.4 Hz), 4.43 (2H, s), 3.91 (2H, d, J=11.8 Hz), 3.74 (2H, t, J=11.8 Hz), 3.20 (2H, d, J=11.6 Hz), 3.12-3.06 (2H, m); m/z (ES+) 457 [MH+].

Workup

  1. stirringstirring
  2. waitcontinued for 2 days
  3. extractionthe products extracted into dichloromethane
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (90% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-4bdae249c87d4583a540e69462a4a732
Source dataset
uspto-grants-2008_12
Patent number
US07468393B2

Reaction notes

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