1-Hydroxybenzotriazole → HCID 178445642, compound

HRID 1633957Notes

Reaction equation

HRID 1633957 reaction equation
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([CH:11]([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=2)=[O:28])[C:12]2[CH:25]=[CH:24][C:15]([C:16]([NH:18][CH2:19][CH2:20][C:21]([OH:23])=O)=[O:17])=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[OH:41][N:42]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.C[Si](C)(C)ON>CN(C=O)C>[C:1]([C@H:5]1[CH2:6][CH2:7][C@H:8]([CH:11]([NH:26][C:27]([NH:29][C:30]2[CH:31]=[CH:32][C:33]([O:36][C:37]([F:40])([F:38])[F:39])=[CH:34][CH:35]=2)=[O:28])[C:12]2[CH:25]=[CH:24][C:15]([C:16]([NH:18][CH2:19][CH2:20][C:21](=[O:23])[NH:42][OH:41])=[O:17])=[CH:14][CH:13]=2)[CH2:9][CH2:10]1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 22501937HCID 22501937, compound

Product 1

HCID 178445642HCID 178445642, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-{4-[1-(4-tert-Butylcyclohexyl)-3-(4-trifluoromethoxyphenyl)ureidomethyl]benzoylamino}-propionic acid (prepared as described in example 92; 0.2 g, 0.36 mmol) was dissolved in DMF (5 mL) and 1-hydroxybenzotriazole (53 mg, 0.39 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (75 mg, 0.39 mmol) were added and the resulting mixture was stirred at room temperature for 30 minutes. The mixture was cooled to 0° C. and N,N-diisopropylethylamine (85 μL, 0.50 mmol) and O-(trimethylsilyl)hydroxylamine (60 μL, 0.50 mmol) were added and the mixture was stirred at room temperature for 16 hours. The mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (50 mL) and was washed with a saturated aqueous solution of sodium chloride (50 mL). The aqueous phase was extracted with ethyl acetate (2×50 mL) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and glacial acetic acid (9:1). This afforded 95 mg (46%) of the title compound as a solid.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringthe mixture was stirred at room temperature for 16 hours
  3. concentrationThe mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
  5. washwas washed with a saturated aqueous solution of sodium chloride (50 mL)
  6. extractionThe aqueous phase was extracted with ethyl acetate (2×50 mL)
  7. dry with materialthe combined organic extracts were dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and glacial acetic acid (9:1)

Sources & evidence

ORD record
ord-13268ec8bde64fc88dc8b8b0ead84d66
Source dataset
uspto-grants-2003_01
Patent number
US06503949B1

Reaction notes

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