Diisopropylethylamine → HCID 59553169, compound

HRID 1641290Notes

Reaction equation

HRID 1641290 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH2:13][C:14]#[N:15])=[CH:4][CH:3]=1.[F:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([N:26]2[CH2:31][CH2:30][CH:29]([CH3:32])[CH2:28][CH2:27]2)[CH:25]=1)[C:20](O)=[O:21].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(OCC)(=O)C>[C:14]([CH2:13][O:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([NH:1][C:20](=[O:21])[C:19]2[CH:23]=[C:24]([N:26]3[CH2:27][CH2:28][CH:29]([CH3:32])[CH2:30][CH2:31]3)[CH:25]=[C:17]([F:16])[CH:18]=2)=[CH:3][CH:4]=1)#[N:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59553077(4-Aminonaphthalen-1-yloxy)-acetonitrileHCID 595533113-Fluoro-5-(4-methylpiperidin-1-yl)benzoic acid

Product 1

HCID 59553169HCID 59553169, compoundYield 18.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-Aminonaphthalen-1-yloxy)-acetonitrile (1.068 g, 5.4 mmol), 3-fluoro-5-(4-methylpiperidin-1-yl)-benzoic acid (1.27 g, 5 4 mmol), diisopropylethylamine (3 ml) and HBTU (2.45 g, 6.5 mmol) are stirred at room temperature in anhydrous dimethylformamide (20 ml) for 1 day. The mixture is then poured into ethyl acetate (200 ml) and washed with water (2×200 ml). The organic layer is then dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with 25-30% ethyl acetate in hexanes to give a pale purple solid. This is then recrystalized from ethyl acetate/methanol to give N-(4-cyanomethoxynaphthalen-1-yl)-3-fluoro-5-(4-methylpiperidin-1-yl)-benzamide as a pale purple solid (303 mg). 1H NMR 300 MHz (CDCl3) 8.27(d, 1H, J=7.5 Hz), 7.94(s, 1H), 7.86(t, 2H, J=9.6 Hz), 7.6(m, 2H), 7.3(s, 1H), 6.97(m, 2H), 6.77(d, 1H, J=11.4 Hz), 5.0(s, 1H), 3.77(m, 2H), 2.83(m, 2H), 1.75(m, 2H), 1.25-1.4(m, 3H), 1.0(d, 3H).

Workup

  1. washwashed with water (2×200 ml)
  2. dry with materialThe organic layer is then dried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe residue is purified by column chromatography on silica gel
  5. washeluted with 25-30% ethyl acetate in hexanes
  6. customto give a pale purple solid
  7. customThis is then recrystalized from ethyl acetate/methanol

Sources & evidence

ORD record
ord-dbf128f90647442ab867bb92ef262de0
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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