1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(1-(3-Amino-4-methylbenzoyl)azepan-4-yl)benzonitrile

HRID 541218Notes

Reaction equation

HRID 541218 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.[NH:12]1[CH2:18][CH2:17][CH2:16][CH:15]([C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[CH2:14][CH2:13]1.OC1C2N=NNC=2C=CC=1.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C.CN(C=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([N:12]1[CH2:18][CH2:17][CH2:16][CH:15]([C:19]2[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[CH:25][CH:26]=2)[CH2:14][CH2:13]1)=[O:7]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 755683-Amino-4-methylbenzoic acidHCID 81531DiisopropylethylamineHCID 682889074-(Azepan-4-yl)benzonitrile2×HCID 178418300HCID 178418300, compound

Product 1

HCID 682889154-(1-(3-Amino-4-methylbenzoyl)azepan-4-yl)benzonitrileYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 4-mL vial was added 3-amino-4-methylbenzoic acid (27 mg, 0.18 mmol, 1.0 equiv), 4-(azepan-4-yl)benzonitrile (compound 40.4, 40 mg, 0.2 mmol, 1.1 equiv), hydroxybenzotriazole (39 mg of 20 wt % H2O, 0.23 mmol, 1.3 equiv), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (44 mg, 0.23 mmol, 1.3 equiv), DMF (1 mL) and N,N-diisopropylethylamine (93 μL, 0.54 mmol, 3.0 equiv). The mixture was stirred at room temperature for 4 hours then diluted into ethyl acetate (10 mL) and washed with brine (10 mL). The aqueous was extracted with ethyl acetate (3 mL) and the combined organics were washed with brine (10 mL), 1 M NaH2PO4 (5 mL) and brine (10 mL). The organics were dried (Na2SO4), filtered and concentrated to obtain the title compound as a brown solid (45 mg, 74%). m/z (ES+) 334 (M+H)+.

Workup

  1. washwashed with brine (10 mL)
  2. extractionThe aqueous was extracted with ethyl acetate (3 mL)
  3. washthe combined organics were washed with brine (10 mL), 1 M NaH2PO4 (5 mL) and brine (10 mL)
  4. dry with materialThe organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-32b2a822a30f4affaec8519f8ecc72f2
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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