Triethylamine → HCID 57951070, compound

HRID 530947Notes

Reaction equation

HRID 530947 reaction equation
Cl.[F:2][C:3]([F:27])([F:26])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[N:18]=[CH:19][C:20]([C:23](O)=[O:24])=[N:21][CH:22]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C(N(CC)CC)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:58][CH:59]1[CH2:64][CH2:63][N:62]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:61][CH2:60]1>CN(C)C=O>[F:26][C:3]([F:2])([F:27])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[N:18]=[CH:19][C:20]([C:23]([NH:58][CH:59]4[CH2:60][CH2:61][N:62]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:63][CH2:64]4)=[O:24])=[N:21][CH:22]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66883338HCID 66883338, compound

Product 1

HCID 57951070HCID 57951070, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)pyrazine-2-carboxylic acid hydrochloric acid salt (0.10 g, 0.25 mmol) in anhydrous N,N-dimethylformamide (3 mL) was added triethylamine (0.56 g, 0.55 mmol), 1-hydroxybenzotriazole hydrate (0.04 g, 0.3 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.06 g, 0.3 mmol), and tert-butyl 4-aminopiperidine-1-carboxylate (0.06 g, 0.3 mmol). The mixture was stirred at room temperature overnight and then concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, ethyl acetate/hexanes=1/1) to afford tert-butyl 4-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)pyrazine-2-carboxamido)piperidine-1-carboxylate (compound 19) as a white solid (0.06 g, 44%). 1H-NMR (CDCl3, 300 MHz): δ 8.89 (m, 1H), 8.06 (m, 1H), 7.50 (m, 3H), 6.96 (m, 2H), 5.33 (m, 1H), 4.10 (m, 3H), 3.64 (m, 2H), 3.25 (m, 2H), 2.95 (m, 2H), 2.15 (m, 2H), 1.97 (m, 4H), 1.56 (m, 2H), 1.47 (s, 9H) ppm; MS (ESI): 550.7 (M+1).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue obtained
  3. customwas purified by flash chromatography (silica gel, ethyl acetate/hexanes=1/1)

Sources & evidence

ORD record
ord-012dc861243b4b63997a96de835e2a90
Source dataset
uspto-grants-2016_05
Patent number
US09353111B2

Reaction notes

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