Acetic Acid → 5-Cyano-furan-2-carboxylic acid (5-hydroxymethyl-2-(4-methyl-piperidin-1-YL)-phenyl)-amide

HRID 33470Notes

Reaction equation

HRID 33470 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][OH:15])=[CH:10][C:9]=2[N+:16]([O-])=O)[CH2:4][CH2:3]1.C(O)(=O)C.[H][H].NC1C=C(CO)C=CC=1N1CCC(C)CC1.[C:41]([C:43]1[O:47][C:46]([C:48](Cl)=[O:49])=[CH:45][CH:44]=1)#[N:42].N1CCOCC1>[Pd].C(Cl)Cl.C(OCC)(=O)C.CO>[OH:15][CH2:14][C:11]1[CH:12]=[CH:13][C:8]([N:5]2[CH2:6][CH2:7][CH:2]([CH3:1])[CH2:3][CH2:4]2)=[C:9]([NH:16][C:48]([C:46]2[O:47][C:43]([C:41]#[N:42])=[CH:44][CH:45]=2)=[O:49])[CH:10]=1

Participants

11

Reactant 6

HCID 176Acetic AcidHCID 8083MorpholineHCID 202590395-Cyano-2-furoyl chlorideHCID 28963353(4-(4-Methylpiperidin-1-yl)-3-nitrophenyl)methanolHCID 59796772(3-Amino-4-(4-methylpiperidin-1-yl)phenyl)methanolHCID 178418361HCID 178418361, compound

Product 1

HCID 98843185-Cyano-furan-2-carboxylic acid (5-hydroxymethyl-2-(4-methyl-piperidin-1-YL)-phenyl)-amide

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 5% Pd/C (5.0 mg, 2.3×10−3 mmol), [4-(4-methyl-piperidin-1-yl)-3-nitro-phenyl]-methanol (i) (95 mg, 0.38 mmol), acetic acid (“HOAc”) (23 mg, 0.38 mmol), methanol (1 mL) and ethyl acetate (4 mL) was stirred in an atmosphere of hydrogen for 3 h. The reaction was filtered, concentrated in vacuo and the resulting [3-amino-4-(4-methyl-piperidin-1-yl)-phenyl]-methanol was used in the next step without further purification. A suspension of [3-amino-4-(4-methyl-piperidin-1-yl)-phenyl]-methanol, 5-cyano-2-furoyl chloride (64 mg, 0.44 mmol), PS morpholine (600 mg, 1.50 mmol), and DCM (10 mL) was stirred at room temperature for 30 min. The reaction was evaporated onto celite, and purified by column chromatography to give 5-cyano-furan-2-carboxylic acid [5-hydroxymethyl-2-(4-methyl-piperidin-1-yl)-phenyl]-amide. MS: 340 (M+1), 1H NMR (CDCl3, 300 MHz): δ 9.9 (s br, 1H), 8.4 (s, 1H), 7.3 (s, 1H), 7.25-7.1 (m, 3H), 4.7 (s, 2H), 3.0 (m, 2H), 2.8 (m, 2H), 1.9, (d, 2H), 1.8-1.4 (m, 3H), 1.1 (d, 3H).

Workup

  1. filtrationThe reaction was filtered
  2. concentrationconcentrated in vacuo
  3. customthe resulting [3-amino-4-(4-methyl-piperidin-1-yl)-phenyl]-methanol was used in the next step without further purification
  4. customThe reaction was evaporated onto celite
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-0fe62a448c1f4b8fa65f1c62f71bbf5b
Source dataset
uspto-grants-2008_09
Patent number
US07429603B2

Reaction notes

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