1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178494304, compound

HRID 541366Notes

Reaction equation

HRID 541366 reaction equation
[CH:1]1([C:5]2[C:13]([C:14]3[NH:18][C:17]([O:19][CH3:20])=[N:16][N:15]=3)=[CH:12][C:8]([C:9]([OH:11])=O)=[C:7]([CH3:21])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH:53]1[CH2:58][CH2:57][CH:56]([C:59]2[CH:66]=[CH:65][C:62]([C:63]#[N:64])=[CH:61][CH:60]=2)[CH2:55][CH2:54]1>CN(C)C=O.C(OCC)(=O)C>[CH:1]1([C:5]2[C:13]([C:14]3[NH:18][C:17]([O:19][CH3:20])=[N:16][N:15]=3)=[CH:12][C:8]([C:9]([N:53]3[CH2:58][CH2:57][CH:56]([C:59]4[CH:66]=[CH:65][C:62]([C:63]#[N:64])=[CH:61][CH:60]=4)[CH2:55][CH2:54]3)=[O:11])=[C:7]([CH3:21])[CH:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178494309HCID 178494309, compound2×

Product 1

HCID 178494304HCID 178494304, compoundYield 23,049%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-cyclobutyl-5-(5-methoxy-4H-1,2,4-triazol-3-yl)-2-methylbenzoic acid (compound 222.3, 60 mg, 0.2 μmol), DIEA (0.11 ml, 0.63 mmol), HOBT (53 mg, 0.32 mmol, with 20% water), EDCI (60 mg, 0.32 mmol) and 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 47 mg, 0.21 mmol) in N,N-dimethylformamide (3 mL) was stirred overnight at room temperature. The reaction mixture was then diluted with 50 mL of ethyl acetate and washed with 2×20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was applied onto a silica gel prep-TLC plate and developed using ethyl acetate/hexanes (1:1) to yield 21.0 mg (22%) of the title compound as a white solid. m/z (ES+) 456 (M+H)+. 1H NMR (400 MHz, Chloroform-d) 611.54-10.86 (br s, 1H), 7.60 (d, 2H), 7.38-7.20 (m, 4H), 5.04-4.92 (m, 1H), 4.06 (s, 3H), 4.14-4.00 (m, 1H), 3.62 (d, 1H), 3.15-3.03 (m, 1H), 2.93-2.76 (m, 2H), 2.38 and 2.30 (2 singlets, amide rotamers, ArCH3, 3H), 2.34-2.22 (m, 1H), 2.20-2.06 (m, 2H), 2.05-1.84 (m, 3H), 1.61-1.45 (m, 1H).

Workup

  1. washwashed with 2×20 mL of brine
  2. dry with materialThe mixture was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-14b9554d29a8440090c4c47b5423bb54
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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