1-Hydroxybenzotriazole → HCID 117643868, compound

HRID 2169577Notes

Reaction equation

HRID 2169577 reaction equation
Br[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)=[N:6][CH:7]=1.O[N:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2N=N1.Cl.[CH2:29](N=C=NCCCN(C)C)[CH3:30].[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([C@@H:47]([NH2:49])[CH3:48])=[CH:43][CH:42]=1>C1COCC1>[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([C@@H:47]([N:49]2[C:15](=[O:17])[C@@H:10]3[CH2:11][O:12][CH2:13][CH2:14][N:9]3[C:3]3[N:4]=[C:5]([C:27]4[CH:26]=[CH:25][CH:24]=[C:23]5[C:22]=4[CH:29]=[CH:30][NH:19]5)[N:6]=[CH:7][C:2]2=3)[CH3:48])=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1550852(S)-(-)-1-(4-chlorophenyl)ethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 88868320HCID 88868320, compound

Product 1

HCID 117643868HCID 117643868, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 50 mL round-bottom flask were added (S)-4-(5-bromo-2-chloropyrimidin-4-yl)morpholine-3-carboxylic acid (560 mg, 1.736 mmol), 1-hydroxybenzotriazole (235 mg, 1.736 mmol), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (399 mg, 2.083 mmol) in THF (10 mL) at 0° C. to give a beige solution. After 5 minutes, (S)-1-(4-chlorophenyl)ethylamine (0.268 mL, 1.910 mmol) was added to the solution, which was allowed to react at 0° C. for 2 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 for 20 minutes) to give the title compound as a white foam (701 mg, 88%). 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 0° C. for 2 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 for 20 minutes)

Sources & evidence

ORD record
ord-f7a32a90bb824cc8815ea7b63dcbc0df
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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