1-Hydroxybenzotriazole → HCID 18374593, compound

HRID 2300714Notes

Reaction equation

HRID 2300714 reaction equation
[CH2:1]([C:5]1([CH2:40][CH3:41])[CH2:11][S:10](=[O:13])(=[O:12])[C:9]2[CH:14]=[CH:15][C:16]([N:18]([CH3:20])[CH3:19])=[CH:17][C:8]=2[CH:7]([C:21]2[CH:22]=[C:23]([NH:27][C:28]([CH2:30][O:31][CH2:32][CH2:33][O:34][CH2:35][C:36](O)=[O:37])=[O:29])[CH:24]=[CH:25][CH:26]=2)[CH:6]1[OH:39])[CH2:2][CH2:3][CH3:4].[NH2:42][CH2:43][C:44]1[CH:49]=[CH:48][C:47]([N:50]2[CH:53]([C:54]3[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][CH:55]=3)[CH:52]([CH2:62][CH2:63][CH:64]([C:66]3[CH:71]=[CH:70][C:69]([F:72])=[CH:68][CH:67]=3)[OH:65])[C:51]2=[O:73])=[CH:46][CH:45]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH2:1]([C:5]1([CH2:40][CH3:41])[CH2:11][S:10](=[O:13])(=[O:12])[C:9]2[CH:14]=[CH:15][C:16]([N:18]([CH3:20])[CH3:19])=[CH:17][C:8]=2[CH:7]([C:21]2[CH:22]=[C:23]([NH:27][C:28]([CH2:30][O:31][CH2:32][CH2:33][O:34][CH2:35][C:36]([NH:42][CH2:43][C:44]3[CH:49]=[CH:48][C:47]([N:50]4[C:51](=[O:73])[CH:52]([CH2:62][CH2:63][CH:64]([C:66]5[CH:67]=[CH:68][C:69]([F:72])=[CH:70][CH:71]=5)[OH:65])[CH:53]4[C:54]4[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][CH:55]=4)=[CH:46][CH:45]=3)=[O:37])=[O:29])[CH:24]=[CH:25][CH:26]=2)[CH:6]1[OH:39])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 121116221-(4-Aminomethylphenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-methoxyphenyl)azetidin-2-oneHCID 18374578HCID 18374578, compound

Product 1

HCID 18374593HCID 18374593, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

At room temperature, 140 mg of (2-{[3-(3-butyl-7-dimethylamino-3-ethyl-4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]thiepin-5-yl)-phenylcarbamoyl]methoxy}-ethoxy)acetic acid (17) and 100 mg of 1-(4-aminomethylphenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-methoxyphenyl)azetidin-2-one are dissolved in 5 ml of dimethylformamide, 35 mg of 1-hydroxybenzotriazole and 45 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride are added and the mixture is stirred at room temperature for 6 h. The reaction mixture is concentrated under reduced pressure. Dichloromethane is added to the residue, the mixture is extracted twice with water and once with sat. sodium chloride solution and the organic extract is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product is purified chromatographically (RP18; dichloromethane/methanol 92/8, changed over 25 min to dichloromethane/methanol 96/4). This gives the product of melting point 116-125° C. Molecular weight 1007.24 (C56H67FN4O10S); MS (ESI): 1008.53 (M+H+).

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure
  2. additionDichloromethane is added to the residue
  3. extractionthe mixture is extracted twice with water and once with sat. sodium chloride solution
  4. extractionthe organic extract
  5. dry with materialis dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product is purified chromatographically (RP18; dichloromethane/methanol 92/8, changed over 25 min to dichloromethane/methanol 96/4)
  9. customThis gives the product of melting point 116-125° C

Sources & evidence

ORD record
ord-974e0278fe06485794605ab47a566eeb
Source dataset
uspto-grants-2002_12
Patent number
US06498156B2

Reaction notes

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