4-Fluoro-n-hydroxybenzimidamide → (R)-1-(3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

HRID 2099841Notes

Reaction equation

HRID 2099841 reaction equation
[CH3:1][C:2]1[C:10]2[C:6](=[CH:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:9]=2)[CH:5]=[C:4]([CH2:19][C@@H:20]([O:24][C:25]([N:27]2[CH2:32][CH2:31][CH:30]([C:33]3[C:34](=[O:43])[NH:35][C:36]4[C:41]([CH:42]=3)=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH2:29][CH2:28]2)=[O:26])[C:21]([OH:23])=O)[CH:3]=1.[F:44][C:45]1[CH:54]=[CH:53][C:48]([C:49](=[N:51]O)[NH2:50])=[CH:47][CH:46]=1.Cl.CN(C)CCCN=C=NCC>COCCOCCOC>[O:43]=[C:34]1[C:33]([CH:30]2[CH2:29][CH2:28][N:27]([C:25]([O:24][C@@H:20]([C:21]3[O:23][N:51]=[C:49]([C:48]4[CH:53]=[CH:54][C:45]([F:44])=[CH:46][CH:47]=4)[N:50]=3)[CH2:19][C:4]3[CH:3]=[C:2]([CH3:1])[C:10]4[C:6](=[CH:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:16])([CH3:18])[CH3:17])[N:9]=4)[CH:5]=3)=[O:26])[CH2:32][CH2:31]2)=[CH:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35]1

Participants

5

Reactant 3

HCID 5930004-Fluoro-n-hydroxybenzimidamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57794582HCID 57794582, compound

Product 1

HCID 57794682(R)-1-(3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent

Conditions

Temperature
110 °C

Procedure

A stirred solution of (R)-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carbonyloxy)propanoic acid (22.4 mg, 0.0370 mmol) in anhydrous diglyme (2 mL) was treated with 4-fluorobenzamidoxime (5.3 mg, 0.0389 mmol) and 1-[3-(dimethylamino)propyl]3-ethylcarbodiimide hydrochloride (7.5 mg, 0.0389 mmol) to at room temperature. The mixture was stirred overnight. The stirred mixture was then heated to 110° C. overnight. After cooling to room temperature, the solvent was removed in vacuo and the crude product was purified using preparative HPLC to afford a tan gum (16.2 mg, 61%). 1H-NMR (CDCl3, 400 MHz) δ 8.8.06 (bs, 2H), 7.88 (s, 1H), 7.69-7.46 (m, 2H), 7.40 (s, 1H), 7.35-7.20 (m,2H), 7.18-7.07 (m, 2H), 7.07 (s, 1H), 6.19-6.15 (m, 1H), 5.79 (s, 2H), 4.40-4.20 (m, 2H), 3.55-3.40 (m, 4H), 3.20-2.83 (m, 4H), 2.70 (s, 3H), 2.72-2.35 (m, 2H), 2.08-1.9 (m, 2H), 0.90-0.77 (m, 2H), −0.11 (s, 9H). Mass spec. 723.3 (MH+).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed in vacuo
  3. customthe crude product was purified

Sources & evidence

ORD record
ord-6d6c4433dc0a47929bdbc315ff137642
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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