1-Hydroxybenzotriazole → HCID 67453605, compound

HRID 1804454Notes

Reaction equation

HRID 1804454 reaction equation
[CH2:1]([C:5]1[C:6]([C:16]([OH:18])=O)=[N:7][O:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH3:4].[Li].O/[N:21]=[C:22](/[C:24]1[CH:41]=[CH:40][C:27]([CH2:28][N:29]2[CH2:32][CH:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30]2)=[CH:26][CH:25]=1)\[NH2:23].Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O>[CH2:1]([C:5]1[C:6]([C:16]2[O:18][N:23]=[C:22]([C:24]3[CH:25]=[CH:26][C:27]([CH2:28][N:29]4[CH2:30][CH:31]([C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])[CH2:32]4)=[CH:40][CH:41]=3)[N:21]=2)=[N:7][O:8][C:9]=1[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3028194LithiumHCID 54846671HCID 54846671, compoundHCID 58504340HCID 58504340, compound

Product 1

HCID 67453605HCID 67453605, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-butyl-5-phenylisoxazole-3-carboxylic acid, lithium salt (0.132 g, 0.523 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Int.1, 0.160 g, 0.523 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.100 g, 0.523 mmol), and HOBt (0.080 g, 0.523 mmol) in N,N-dimethylformamide (4 mL) was stirred at room temperature for 60 min and then heated at 60° C. overnight. The solvent was removed under reduced pressure. The residue was purified by flash silica gel chromatography eluting with 1% methanol in dichloromethane to give tert-butyl 1-(4-(5-(4-butyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (0.156 g) as a pale yellow solid. The ester intermediate was >99% pure by HPLC with a ret. time=3.40 min.−Column. CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=515.0.

Workup

  1. temperatureheated at 60° C. overnight
  2. customThe solvent was removed under reduced pressure
  3. customThe residue was purified by flash silica gel chromatography
  4. washeluting with 1% methanol in dichloromethane

Sources & evidence

ORD record
ord-5de424eb844447c2b2fae26fe29d36c2
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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