Diisopropylethylamine → HCID 178433048, compound

HRID 872797Notes

Reaction equation

HRID 872797 reaction equation
[CH3:1][C:2]1[NH:3][CH:4]=[C:5]([C:7]([OH:9])=O)[N:6]=1.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C.[NH2:55][C@@H:56]([CH3:72])[CH2:57][N:58]1[CH:62]=[CH:61][C:60]([C:63]2[CH:70]=[CH:69][C:66]([C:67]#[N:68])=[C:65]([Cl:71])[CH:64]=2)=[N:59]1>CN(C)C=O.O>[Cl:71][C:65]1[CH:64]=[C:63]([C:60]2[CH:61]=[CH:62][N:58]([CH2:57][C@@H:56]([NH:55][C:7]([C:5]3[N:6]=[C:2]([CH3:1])[NH:3][CH:4]=3)=[O:9])[CH3:72])[N:59]=2)[CH:70]=[CH:69][C:66]=1[C:67]#[N:68]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrileHCID 178433052HCID 178433052, compound

Product 1

HCID 178433048HCID 178433048, compoundYield 71.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Methyl-1H-imidazole-4-carboxylic acid (1.364 g, 10.82 mmol) was suspended in N,N-Dimethyl formamide (25 ml). 0-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (0.342 g, 0.901 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.073 g, 10.82 mmol), DIPEA (3.14 ml, 18.03 mmol) and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (2.5 g, 9.01 mmol) were rapidly added into the mixture, respectively. The reaction mixture was stirred at RT overnight. Next day water was slowly added and the mixture was extracted twice with DCM. The combined organic phases were extracted three times with water and the DCM-layer was evaporated. The product was crystallized from acetonitrile/water mixture and finally dried with vacuum at 40° C. Yield 71.6%. 1H-NMR (400 MHz; d6-DMSO): δ 1.08 (d, 3H), 2.31 (s, 3H), 4.27 (dd, 1H), 4.32-4.48 (m, 2H), 6.95 (d, 1H), 7.41 (s, 1H), 7.82 (d, 1H), 7.95-8.02 (m, 2H), 8.04 (d, 1H), 8.10 (m, 1H), 12.10 (bs, 1H).

Workup

  1. extractionthe mixture was extracted twice with DCM
  2. extractionThe combined organic phases were extracted three times with water
  3. customthe DCM-layer was evaporated
  4. customThe product was crystallized from acetonitrile/water mixture
  5. customfinally dried with vacuum at 40° C

Sources & evidence

ORD record
ord-f8f663e9b5d14e53a00ccad4b3c8d697
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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