1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Ethyl 3-(2-(3-(4-fluorophenyl)-1H-pyrazol-1-yl)nicotinamido)-2-hydroxy-4-phenylbutanoate

HRID 1908260Notes

Reaction equation

HRID 1908260 reaction equation
Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:35]=[CH:34][N:33]([C:36]3[N:44]=[CH:43][CH:42]=[CH:41][C:37]=3[C:38]([OH:40])=O)[N:32]=2)=[CH:27][CH:26]=1.[Cl-].[CH2:46]([O:48][C:49](=[O:61])[CH:50]([OH:60])[CH:51]([NH3+:59])[CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[CH3:47]>ClCCl.COC(C)(C)C.CCN(CC)CC>[F:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]2[CH:35]=[CH:34][N:33]([C:36]3[N:44]=[CH:43][CH:42]=[CH:41][C:37]=3[C:38]([NH:59][CH:51]([CH2:52][C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)[CH:50]([OH:60])[C:49]([O:48][CH2:46][CH3:47])=[O:61])=[O:40])[N:32]=2)=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67238800HCID 67238800, compoundHCID 86644788HCID 86644788, compound

Product 1

HCID 67239028Ethyl 3-(2-(3-(4-fluorophenyl)-1H-pyrazol-1-yl)nicotinamido)-2-hydroxy-4-phenylbutanoateYield 69.4%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
5 °C

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) (4.47 g, 23.3 mmol), 1-hydroxybenzotriazole hydrate (HOBt) (3.57 g, 23.3 mmol) and triethylamine (Et3N) (4.5 ml, 32.3 mmol) were successively added to a solution of 2-(3-(4-fluorophenyl)-1H-pyrazol-1-yl)nicotinic acid (6.0 g, 21.8 mmol) and 4-ethoxy-3-hydroxy-4-oxo-1-phenylbutan-2-aminium chloride (6.60 g, 25.4 mmol) in dichloromethane (300 ml) at 5° C., and the mixture was stirred at 5° C. for about 5 minutes. A pH of 10 was adjusted by adding 6 ml Et3N, the mixture stirred for 1 h at 5° C. and then overnight at room temperature. The mixture then was concentrated under reduced pressure, poured into 1000 ml of water, the precipitate formed was filtered off with suction and dried in vacuo to give 7.8 g, which were treated 100 ml of methyl-tert.butylether to give 7.39 g of the desired product; ESI-MS [M+H]+: 489.2.

Workup

  1. stirringthe mixture stirred for 1 h at 5° C.
  2. customovernight
  3. customat room temperature
  4. concentrationThe mixture then was concentrated under reduced pressure
  5. additionpoured into 1000 ml of water
  6. customthe precipitate formed
  7. filtrationwas filtered off with suction
  8. customdried in vacuo
  9. customto give 7.8 g, which

Sources & evidence

ORD record
ord-404cd48260e145f68a2aceddca494596
Source dataset
uspto-grants-2013_12
Patent number
US08598211B2

Reaction notes

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