1-Hydroxybenzotriazole → HCID 88868455, compound

HRID 2169576Notes

Reaction equation

HRID 2169576 reaction equation
[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[C:15]([OH:17])=O)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([C@@H:47]([NH2:49])[CH3:48])=[CH:43][CH:42]=1>C1COCC1>[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH:10]2[C:15]([NH:49][C@H:47]([C:44]2[CH:45]=[CH:46][C:41]([Cl:40])=[CH:42][CH:43]=2)[CH3:48])=[O:17])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1550852(S)-(-)-1-(4-chlorophenyl)ethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 88868110HCID 88868110, compound

Product 1

HCID 88868455HCID 88868455, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 50 mL round-bottom flask were added (R)-4-(5-bromo-2-chloropyrimidin-4-yl)morpholine-3-carboxylic acid (460 mg, 1.426 mmol), 1-hydroxybenzotriazole (193 mg, 1.426 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (328 mg, 1.711 mmol) in THF (10 mL) to give a beige solution. After 5 minutes (S)-1-(4-chlorophenyl)ethylamine (0.220 mL, 1.569 mmol) was added to the solution, which was allowed to react at room temperature for 1.5 hours. The reaction mixture was subsequently partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by normal phase column chromatography (20-50% EtOAc gradient in hexanes over 20 minutes) to give a diastereomeric mixture of the title compound as a white foam (474 mg, 72.2%). 1H NMR (400 MHz, DMSO-d6) δ 1.35-1.42 (m, 3H), 3.50-3.63 (m, 2H), 3.69-3.79 (m, 1H), 3.83-3.93 (m, 1H), 4.23-4.39 (m, 2H), 4.85-4.89 (m, 1H), 4.90-5.03 (m, 1H), 7.33-7.41 (m, 4H), 8.44-8.48 (m, 1H), 8.48-8.57 (m, 1H). ESI-MS m/z [M+H]+ calc'd for C17H17BrCl2N4O2, 458.99; found 459.3.

Workup

  1. customto give a beige solution
  2. customto react at room temperature for 1.5 hours
  3. customThe reaction mixture was subsequently partitioned between brine and ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by normal phase column chromatography (20-50% EtOAc gradient in hexanes over 20 minutes)
  9. customto give

Sources & evidence

ORD record
ord-0045c59d76d34df38715b8c5ecadc3f1
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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