1-Hydroxybenzotriazole → HCID 86670123, compound

HRID 2169579Notes

Reaction equation

HRID 2169579 reaction equation
[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH: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.[O:40]1[CH2:45][CH2:44][CH:43]([NH2:46])[CH2:42][CH2:41]1>O1CCCC1>[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH:10]2[C:15]([NH:46][CH:43]2[CH2:44][CH2:45][O:40][CH2:41][CH2:42]2)=[O:17])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 4192234-AminotetrahydropyranHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86670107HCID 86670107, compound

Product 1

HCID 86670123HCID 86670123, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 200 mL round-bottom flask were added 4-(5-bromo-2-chloropyrimidin-4-yl)morpholine-3-carboxylic acid (PREPARATION x30, 2.5 g, 7.75 mmol) and 1-hydroxybenzotriazole (1.257 g, 9.30 mmol) in tetrahydrofuran (30 mL) to give a beige suspension. To this suspension were added 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.783 g, 9.30 mmol) and tetrahydro-2H-pyran-4-amine (0.802 mL, 7.75 mmol). After 1 hour at 0° C., HPLC showed the reaction was almost complete. 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 (˜50 g silica, 35-100% EtOAc gradient in hexanes) to give the title compound as a white foam (1.8 g, 57.2%).

Workup

  1. customto give a beige suspension
  2. customThe reaction mixture was subsequently partitioned between brine and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by normal phase column chromatography (˜50 g silica, 35-100% EtOAc gradient in hexanes)

Sources & evidence

ORD record
ord-1b07bfe02c5b4d7095370746dee60b08
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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