1-Hydroxybenzotriazole → Tert-butyl 1-(4-(5-(4-propyl-3-(pyridin-2-yl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

HRID 1951952Notes

Reaction equation

HRID 1951952 reaction equation
[CH2:1]([C:4]1[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:6][O:7][C:8]=1[C:9]([OH:11])=O)[CH2:2][CH3:3].[Li].O[N:20]=[C:21]([C:23]1[CH:40]=[CH:39][C:26]([CH2:27][N:28]2[CH2:31][CH:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]2)=[CH:25][CH:24]=1)[NH2:22].N1C=CC=CC=1C1C(C(F)(F)F)=C(C2ON=C(C3C=CC(CN4CC(C(O)=O)C4)=CC=3)N=2)ON=1.C1C=CC2N(O)N=NC=2C=1.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C>C(#N)C>[CH2:1]([C:4]1[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:6][O:7][C:8]=1[C:9]1[O:11][N:22]=[C:21]([C:23]2[CH:24]=[CH:25][C:26]([CH2:27][N:28]3[CH2:29][CH:30]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:31]3)=[CH:39][CH:40]=2)[N:20]=1)[CH2:2][CH3:3]

Participants

9

Reactant 7

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3028194LithiumHCID 468359141-(4-(5-(3-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acidHCID 580628284-Propyl-3-(pyridin-2-yl)isoxazole-5-carboxylic acidHCID 76806751tert-butyl 1-[[4-(N'-hydroxycarbamimidoyl)phenyl]methyl]azetidine-3-carboxylate

Product 1

HCID 66678205Tert-butyl 1-(4-(5-(4-propyl-3-(pyridin-2-yl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-propyl-3-(pyridin-2-yl)isoxazole-5-carboxylic acid, lithium salt (13.5 mg, 0.058 mmol), tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int. 1 (7.8 mg, 0.058 mmol), HOBt (16.02 mg, 0.105 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (26.1 mg, 0.136 mmol), and diisopropylethylamine (0.041 mL, 0.233 mmol) in acetonitrile (1 mL) was stirred at 80° C. for 2 h. The reaction mixture was concentrated, and the residue was diluted with ethyl acetate (3 mL), washed a saturated aqueous solution of sodium bicarbonate (1 mL), washed with water (1 mL), washed with brine (1 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by preparative HPLC afforded tert-butyl 1-(4-(5-(4-propyl-3-(pyridin-2-yl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with ethyl acetate (3 mL)
  3. washwashed a saturated aqueous solution of sodium bicarbonate (1 mL)
  4. washwashed with water (1 mL)
  5. washwashed with brine (1 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationConcentration
  8. customfollowed by purification by preparative HPLC

Sources & evidence

ORD record
ord-7084c964d1a948a7a2f9e7ad3e6babdc
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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