Triethylamine → HCID 25112583, compound

HRID 1367110Notes

Reaction equation

HRID 1367110 reaction equation
[N:1]1([CH2:6][C@H:7]2[CH2:11][CH2:10][C@@H:9]([N:12]([CH2:20][C:21](O)=[O:22])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]2)[CH:5]=[N:4][CH:3]=[N:2]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:57][C@@H:58]1[CH2:62][NH:61][C@H:60]([C:63]([NH2:65])=[O:64])[CH2:59]1.C(N(CC)CC)C>ClCCl.O>[N:1]1([CH2:6][C@H:7]2[CH2:11][CH2:10][C@@H:9]([N:12]([CH2:20][C:21]([N:61]3[CH2:62][C@@H:58]([F:57])[CH2:59][C@H:60]3[C:63]([NH2:65])=[O:64])=[O:22])[C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:8]2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 25050111HCID 25050111, compoundHCID 25112582HCID 25112582, compound

Product 1

HCID 25112583HCID 25112583, compoundYield 74.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a stirred and cooled (0° C.) mixture of [(3S,1R)-3-(1H-1,2,4-Triazol-1-ylmethyl)-cyclopentyl-N—BOC-amino]-acetic acid (10 g, 30.5 mmol) and 1-hydroxybenzotriazole (5 g, 36.9 mmol) in dichloromethane (200 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (7.1 g, 36.9 mmol) in portions and the mixture was stirred for 0.5 h at the same temperature to result a clear solution. A solution of (2S,4S)-4-fluoropyrrolidine-2-carboxamide p-toluenesulfonate (5.71 g, 33.9 mmol) and triethylamine (6.4 ml, 4.62 mmol) in dichloromethane (60 ml) was added and the mixture was stirred for 3 h at room temperature. The reaction mixture was diluted with DCM (100 ml) and water (200 ml) and the layers were separated. The organic layer was washed with 0.5N HCl (100 ml) and then with brine (50 ml). The solvent was evaporated under reduced pressure to give 10 g of the product as a white solid; 1H NMR (300 MHz, CDCl3) δ 1.25-1.33 (m, 2H), 1.42 (s, 9H), 1.70-1.99 (m, 5H), 2.04-2.47 (m, 2H), 2.80-2.82 (m, 1H), 3.63-3.91 (m, 4H), 4.14-4.17 (m, 2H), 4.35-4.37 (m, 2H), 4.74 (d, J=9.6 Hz, 1H), 5.25-5.42 (m, 1H), 7.93 (s, 1H), 8.06 (s, 0.6H, rotomer), 8.08 (s, 0.4H, rotomer).

Workup

  1. temperaturecooled
  2. stirringthe mixture was stirred for 0.5 h at the same temperature
  3. customto result a clear solution
  4. stirringthe mixture was stirred for 3 h at room temperature
  5. customthe layers were separated
  6. washThe organic layer was washed with 0.5N HCl (100 ml)
  7. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-26171c553a0c42d0aa65531838bea329
Source dataset
uspto-grants-2011_02
Patent number
US07893103B2

Reaction notes

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