1-Hydroxybenzotriazole → 2-(4-(7-(4-(2-Butoxyethoxy)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carbonylamino) benzyl)-1,3,2-dioxaphosphorinane-2-oxide

HRID 1978795Notes

Reaction equation

HRID 1978795 reaction equation
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[S:24](=[O:26])(=[O:25])[CH2:23][CH2:22][C:21]([C:27](O)=[O:28])=[CH:20][C:19]=3[CH:30]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].[NH2:31][C:32]1[CH:45]=[CH:44][C:35]([CH2:36][P:37]2(=[O:43])[O:42][CH2:41][CH2:40][CH2:39][O:38]2)=[CH:34][CH:33]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.O.C(N(CC)CC)C>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[S:24](=[O:25])(=[O:26])[CH2:23][CH2:22][C:21]([C:27]([NH:31][C:32]4[CH:45]=[CH:44][C:35]([CH2:36][P:37]5(=[O:43])[O:38][CH2:39][CH2:40][CH2:41][O:42]5)=[CH:34][CH:33]=4)=[O:28])=[CH:20][C:19]=3[CH:30]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 112991132-(4-Aminobenzyl)-1,3,2-dioxaphosphorinane-2-oxideHCID 219957617-(4-(2-Butoxyethoxy)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid

Product 1

HCID 540090722-(4-(7-(4-(2-Butoxyethoxy)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carbonylamino) benzyl)-1,3,2-dioxaphosphorinane-2-oxideYield 67.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

In DMF (8 ml) were dissolved 7-(4-(2-butoxyethoxy)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (0.4 g), 2-(4-aminobenzyl)-1,3,2-dioxaphosphorinane-2-oxide (0.22 g) and 1-hydroxybenzotriazole (0.13 g), and to the solution were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.36 g) and triethylamine (0.4 ml). Under nitrogen atmosphere, the mixture was stirred at room temperature overnight, poured into water and extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, and dried with anhydrous magnesium sulfate. The solvent was evaporated to give crude crystals, which were recrystallized from ethanol to give 2-(4-(7-(4-(2-butoxyethoxy)phenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carbonylamino) benzyl)-1,3,2-dioxaphosphorinane-2-oxide (Compound 156) (0.40 g) as colorless crystals.

Workup

  1. extractionextracted with ethyl acetate
  2. washthe organic layer was washed with water and saturated brine
  3. dry with materialdried with anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customto give crude crystals, which
  6. customwere recrystallized from ethanol

Sources & evidence

ORD record
ord-6130d0dbb1c54b34b45c239db27b72d1
Source dataset
uspto-grants-2001_05
Patent number
US06235771B1

Reaction notes

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