1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178466824, compound

HRID 1409404Notes

Reaction equation

HRID 1409404 reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([C:9]([OH:11])=O)[NH:6][N:5]=1)(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN=C=NCCCN(C)C.[NH2:56][C@@H:57]([CH3:73])[CH2:58][N:59]1[CH:63]=[CH:62][C:61]([C:64]2[CH:71]=[CH:70][C:67]([C:68]#[N:69])=[C:66]([Cl:72])[CH:65]=2)=[N:60]1>C(Cl)Cl>[C:1]([C:4]1[NH:5][N:6]=[C:7]([C:9]([NH:56][C@@H:57]([CH3:73])[CH2:58][N:59]2[CH:63]=[CH:62][C:61]([C:64]3[CH:71]=[CH:70][C:67]([C:68]#[N:69])=[C:66]([Cl:72])[CH:65]=3)=[N:60]2)=[O:11])[CH:8]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167673463-acetyl-1H-pyrazole-5-carboxylic acidHCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile

Product 1

HCID 178466824HCID 178466824, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Acetyl-1H-pyrazole-5-carboxylic acid (10.20 g, 66.2 mmol), DCM (195 ml) and DIPEA (11.52 ml, 66.2 mmol) were placed in to the reaction flask under nitrogen atmosphere. HBTU (3.27 g, 8.63 mmol), EDCI (12.68 g, 66.2 mmol) and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (15 g, 57.5 mmol) were added in this order and the mixture was stirred overnight at RT. The solvent was distilled close to dryness under vacuum, 2-propanol (25 ml) was added and the mixture was distilled to dryness. 2-Propanol (127 ml) was added, heated to reflux, water (23 ml) was added and the mixture was stirred for 15 min. The mixture was cooled to RT, stirred overnight and cooled to 5° C. The precipitate was filtered, washed with 2×10 ml of cold 2-propanol:water (70:30) and dried under vacuum to obtain 18.7 g of the title compound. 1H-NMR (400 MHz, DMSO-d6): δ 1.17 (d, 3H), 2.50 (s, 3H), 4.21-4.53 (m, 3H), 6.93 (d, 1H), 7.31 (s, 1H), 7.81 (d, 1H), 7.86-8.07 (m, 3H), 8.40-8.54 (bs, 1H), 14.14 (bs., 1H).

Workup

  1. distillationThe solvent was distilled
  2. customclose to dryness under vacuum, 2-propanol (25 ml)
  3. additionwas added
  4. distillationthe mixture was distilled to dryness
  5. addition2-Propanol (127 ml) was added
  6. temperatureheated
  7. temperatureto reflux
  8. additionwater (23 ml) was added
  9. stirringthe mixture was stirred for 15 min
  10. temperatureThe mixture was cooled to RT
  11. stirringstirred overnight
  12. temperaturecooled to 5° C
  13. filtrationThe precipitate was filtered
  14. washwashed with 2×10 ml of cold 2-propanol:water (70:30)
  15. customdried under vacuum

Sources & evidence

ORD record
ord-c25b213645534d2fbcf7724d34be7f9e
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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