4-Cyanobenzohydrazide → HCID 59193077, compound

HRID 2388554Notes

Reaction equation

HRID 2388554 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][C@@H:11]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[C:18]([Cl:24])[C:17]=1[CH3:25])[C:12]([OH:14])=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:26]([C:28]1[CH:37]=[CH:36][C:31]([C:32]([NH:34][NH2:35])=[O:33])=[CH:30][CH:29]=1)#[N:27].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>C1COCC1>[Si:1]([O:8][CH2:9][CH2:10][C@@H:11]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[C:18]([Cl:24])[C:17]=1[CH3:25])[C:12]([NH:35][NH:34][C:32](=[O:33])[C:31]1[CH:30]=[CH:29][C:28]([C:26]#[N:27])=[CH:37][CH:36]=1)=[O:14])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 4567324-CyanobenzohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59193041HCID 59193041, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 59193077HCID 59193077, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

(R)-4-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoic acid (840 mg, 2.19 mmol) and 4-cyanobenzohydrazide (329 mg, 2.41 mmol) were mixed together in THF (100 ml) and cooled to −15° C. under N2 atmosphere. To the pre-cooled reaction mixture were added hydroxybenzotriazole (HOBT) (296 mg, 2.19 mmol), TEA (0.458 mL, 3.29 mmol) followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) (630 mg, 3.29 mmol). The reaction mixture was allowed to stir at −20° C. for 20 min and then at room temperature overnight. After the reaction was complete based on TLC, the urea was filtered off and the solution was washed with water, 5% citric acid followed by 5% NaHCO3 to provide the crude product as a yellow solid (0.95 g). Purification by flash column chromatography [EtOAc-hexanes (1:1) as eluent] afforded the title compound as a white crystalline solid (605 mg, 53%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 9.78 (br s, 2H), 8.03 (d, J=9 Hz, 2H), 7.87 (d, J=9 Hz, 2H), 7.48 (d, J=9 Hz, 1H), 6.63 (d, J=9 Hz, 1H), 5.87 (d, J=9 Hz, 1H), 4.40-4.34 (m, 1H), 4.03-3.82 (m, 2H), 2.31 (s, 3H), 2.29-2.04 (m, 2H), 0.81 (s, 9H), 0.1 (s, 3H) and 0.00 (s, 3H).

Workup

  1. customTo the pre-cooled reaction mixture
  2. customat room temperature
  3. customovernight
  4. filtrationthe urea was filtered off
  5. washthe solution was washed with water, 5% citric acid
  6. customto provide the crude product as a yellow solid (0.95 g)
  7. customPurification by flash column chromatography [EtOAc-hexanes (1:1) as eluent]

Sources & evidence

ORD record
ord-48d099a7618442d3b195b91211f3bd7b
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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