1-Hydroxybenzotriazole → HCID 131732929, compound

HRID 2170056Notes

Reaction equation

HRID 2170056 reaction equation
Cl.C(N([CH2:13][CH3:14])CCCN=C=NCC)C.[OH:15]N1C2C=CC=CC=2N=N1.Cl.[NH2:26][C@H:27]([C:30]1[CH:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=1)[CH2:28][OH:29].C(N(CC)C(C)C)(C)C>C1COCC1.O>[OH:29][CH2:28][C@H:27]([NH2:26])[C:30]1[CH:31]=[N:32][C:33]([C:36]([F:37])([F:38])[F:39])=[CH:34][CH:35]=1.[C:35]1([C@H:30]2[CH2:31][C@@H:27]2[C:28]([OH:15])=[O:29])[CH:14]=[CH:13][CH:36]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 99645121-(3-Diethylaminopropyl)-3-ethylcarbodiimide hydrochlorideHCID 71182945HCID 71182945, compound

Product 1

HCID 131732929HCID 131732929, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-(3-Diethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.39 g, 2.03 mmol) and 1-hydroxybenzotriazole (0.366 g, 2.71 mmol) were added to a stirred mixture of IM46 (0.22 g, 1.36 mmol) and commercially available (R)-2-amino-2-(6-trifluoromethyl-pyridin-3-yl)-ethanol hydrochloride (Supplier Netchem Inc., Catalog No 517882) (0.494 g, 2.03 mmol) and N,N-diisopropylethylamine (0.472 ml, 2.71 mmol) in THF (20 ml). The solution was stirred at rt overnight. Water was added and the mixture was extracted with EtOAc (3×80 ml). The combined organic phases were washed with brine, dried over MgSO4, filtered and the solvent was evaporated of in vac. The crude product was purified by silica gel chromatography (EtOAc in heptanes 10:1). Yield of Compound 22 475 mg (78%). 1H-NMR (500 MHz, DMSO) δ 8.77 (d, 1H), 8.74 (s, 1H), 8.00 (d, 1H), 7.88 (d, 1H), 7.27 (m, 2H), 7.18 (m, 1H), 7.13 (d, 2H), 5.04 (m, 2H), 3.64 (m, 2H), 2.22 (m, 1H), 2.07 (m, 1H), 1.37 (m, 1H), 1.37 (m, 1H), 1.23 (m, 1H). LC-MS (m/z) 351.1 (MH+), tR=1.51 min (method A).

Workup

  1. extractionthe mixture was extracted with EtOAc (3×80 ml)
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvent was evaporated of in vac
  6. customThe crude product was purified by silica gel chromatography (EtOAc in heptanes 10:1)

Sources & evidence

ORD record
ord-e507f792f8384876af531c17116638c8
Source dataset
uspto-grants-2015_06
Patent number
US09050327B2

Reaction notes

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