Diisopropylethylamine → HCID 178425804, compound

HRID 1488122Notes

Reaction equation

HRID 1488122 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:17]#[N:18])[NH:5][C:6]=1[C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[CH3:16])[C:10]([OH:12])=O.Cl.[NH:20]1[CH2:25][CH2:24][CH:23]([C:26]2[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][CH:27]=2)[CH2:22][CH2:21]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O.CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([C:17]#[N:18])[NH:5][C:6]=1[C:7]1[CH:8]=[C:9]([C:10]([N:20]2[CH2:25][CH2:24][CH:23]([C:26]3[CH:27]=[CH:28][C:29]([C:30]#[N:31])=[CH:32][CH:33]=3)[CH2:22][CH2:21]2)=[O:12])[CH:13]=[CH:14][C:15]=1[CH3:16]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178425888HCID 178425888, compound2×

Product 1

HCID 178425804HCID 178425804, compoundYield 25.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
15 °C

Procedure

Into a 25-mL round-bottom flask, was placed a solution of 3-(4-chloro-2-cyano-1H-imidazol-5-yl)-4-methylbenzoic acid (compound 234.5, 60 mg, 0.23 mmol) in N,N-dimethylformamide (2 mL). 4-(Piperidin-4-yl)benzonitrile hydrochloride (compound 1.2, 61 mg, 0.27 mmol), HBTU (131 mg, 0.35 mmol), DIEA (123 μL, 0.69 mmol) were added to the reaction. The reaction mixture was stirred for 30 min at 15° C. The reaction mixture was diluted with 40 mL of EtOAc, then was washed with 2×30 mL of brine and 2×30 mL of NH4Cl (sat.), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product (160 mg) was purified by Prep-HPLC with the following conditions (2#-AnalyseHPLC-SHIMADZU(HPLC-10)): Column, SunFire Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, WATER WITH 0.05% TFA and MeCN (49.0% MeCN up to 62.0% in 7 min, up to 100.0% in 3 min, down to 49.0% in 1 min); Detector, Waters 2489, 254 and 220 nm. This resulted in 25.1 mg (25%) of the title compound as a white solid. m/z (ES+) 430 (M+H)+.

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. washwas washed with 2×30 mL of brine and 2×30 mL of NH4Cl (sat.)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product (160 mg) was purified by Prep-HPLC with the following conditions (2#-AnalyseHPLC-SHIMADZU(HPLC-10))
  6. waitmobile phase, WATER WITH 0.05% TFA and MeCN (49.0% MeCN up to 62.0% in 7 min
  7. waitup to 100.0% in 3 min
  8. waitdown to 49.0% in 1 min)

Sources & evidence

ORD record
ord-67a613db726f4c2fb166d8f0cc7548ff
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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