Ethyl Acetate → 3-Fluoro-5-morpholin-4-yl-N-(4-morpholin-4-ylmethyl-naphthalen-1-yl)-benzamide

HRID 1171427Notes

Reaction equation

HRID 1171427 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:22]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](C=O)=[CH:10][CH:9]=1)=[O:6].[C:29]([BH3-])#[N:30].[Na+].[C:33]([O:36][CH2:37][CH3:38])(=O)[CH3:34]>N1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:22]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([CH2:29][N:30]2[CH2:38][CH2:37][O:36][CH2:33][CH2:34]2)=[CH:10][CH:9]=1)=[O:6]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 5003444Sodium cyanoborohydrideHCID 595531113-fluoro-N-(4-formyl-naphthalen-1-yl)-5-morpholin-4-yl-benzamide

Product 1

HCID 595531413-Fluoro-5-morpholin-4-yl-N-(4-morpholin-4-ylmethyl-naphthalen-1-yl)-benzamide

Reagents, catalysts & solvents 1

HCID 8083MorpholineSolvent

Conditions

Temperature
100 °C

Procedure

3-Fluoro-N-(4-formyl-naphthalen-1-yl)-5-morpholin-4-yl-benzamide (100 mg, 264 μmol) in morpholine (2.5 ml) is heated to 100° C. for 2.5 hours. Sodium cyanoborohydride (200 mg) is then added and the mixture heated at 100° C. for an additional 2 hours. The mixture is cooled to room temperature poured into ethyl acetate (100 ml), washed with water (2×50 ml) and brine (50 ml). The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluting with 70% ethyl acetate in hexanes to give product as a white solid (64 mg). Mp: 192-3° C. 1H NMR 400 MHz (CDCl3) δ 8.32 (m, 1H), 8.03 (s, 1H), 7.83 (m, 2H), 7.5 (m, 2H), 7.39 (d, 1H, J=7.6 Hz), 7.24 (s, 1H), 6.98 (d, 1H, J=8 Hz), 6.70 (d, 1H, J=11.6 Hz), 3.8 (m, 6H), 3.62 (t, 4H, J=4.4 Hz), 3.19 (t, 4H, J=4.8 Hz), 2.45 (s, 4H). MS: 450 (M+1).

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. washwashed with water (2×50 ml) and brine (50 ml)
  3. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  4. customevaporated to dryness
  5. customThe residue is purified by column chromatography on silica gel eluting with 70% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3b56a4bff22447958b89e16f44c76b85
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

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