1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178437944, compound

HRID 541304Notes

Reaction equation

HRID 541304 reaction equation
[CH:1]1([C:5]2[C:13]([C:14]3[NH:18][C:17]([CH2:19][CH3:20])=[N:16][N:15]=3)=[CH:12][C:8]([C:9](O)=[O:10])=[C:7]([CH2:21][CH3:22])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[NH:45]1[CH2:50][CH2:49][CH:48]([C:51]2[CH:58]=[CH:57][C:54]([C:55]#[N:56])=[CH:53][CH:52]=2)[CH2:47][CH2:46]1>CN(C)C=O.CN(C1C=CN=CC=1)C>[CH:1]1([C:5]2[C:13]([C:14]3[NH:18][C:17]([CH2:19][CH3:20])=[N:16][N:15]=3)=[CH:12][C:8]([C:9]([N:45]3[CH2:50][CH2:49][CH:48]([C:51]4[CH:58]=[CH:57][C:54]([C:55]#[N:56])=[CH:53][CH:52]=4)[CH2:47][CH2:46]3)=[O:10])=[C:7]([CH2:21][CH3:22])[CH:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178437949HCID 178437949, compound2×

Product 1

HCID 178437944HCID 178437944, compoundYield 40.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4-cyclobutyl-2-ethyl-5-(5-ethyl-4H-1,2,4-triazol-3-yl)benzoic acid (compound 181.9, 160 mg, 0.530 mmol, 1.00 equiv) in N,N-dimethylformamide (20 mL) were added EDCI (113 mg, 0.590 mmol, 1.11 equiv), DMAP (197 mg, 1.62 mmol, 3.03 equiv), and HOBT (87.5 mg, 0.650 mmol, 1.21 equiv). After 5 min, 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 110 mg, 0.590 mmol, 1.10 equiv) was added. The resulting mixture was stirred at 25° C. for 15 h, then quenched with 100 mL of ice water. The mixture was extracted with 2×150 mL of ethyl acetate. The combined organic layers were washed with 3×150 mL of brine, dried over anhydrous sodium sulfate, and concentrated. The crude product (˜150 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (47% CH3CN up to 61% in 6 min, up to 100% in 1.5 min, down to 47% in 1.5 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 99.5 mg (40%) of the title compound as a white solid m/z (ES+) 468 (M+H)+. 1H-NMR (300 MHz, CD3OD): δ 7.71-7.69 (m, 2H), 7.50-7.32 (m, 4H), 4.03-3.99 (m, 1H), 3.65-3.5 (m, 1H), 3.32-3.20 (m, 1H), 2.90-2.95 (m, 4H), 2.70-2.74 (m, 2H), 2.20-1.98 (m, 6H), 1.98-1.79 (m, 4H), 1.41 (t, 3H), 1.39-1.28 (m, 3H).

Workup

  1. customquenched with 100 mL of ice water
  2. extractionThe mixture was extracted with 2×150 mL of ethyl acetate
  3. washThe combined organic layers were washed with 3×150 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product (˜150 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  7. waitmobile phase, water with 0.05% TFA and CH3CN (47% CH3CN up to 61% in 6 min
  8. waitup to 100% in 1.5 min
  9. waitdown to 47% in 1.5 min)
  10. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-b9952789b1f046309e5e321bce3c5477
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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