1,2-Dichloroethane → HCID 178444059, compound

HRID 716384Notes

Reaction equation

HRID 716384 reaction equation
[C:1]([C:5]1[CH:28]=[CH:27][C:8]([C:9]([NH:11][C@H:12]([C:23]([O:25][CH3:26])=[O:24])[CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH2:43]([O:50][C:51]1[CH:60]=[CH:59][C:54](/[C:55](=[N:57]/O)/[NH2:56])=[CH:53][CH:52]=1)[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49]>CN(C=O)C>[C:1]([C:5]1[CH:28]=[CH:27][C:8]([C:9]([NH:11][C@@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][NH:57][C:55](=[NH:56])[C:54]3[CH:53]=[CH:52][C:51]([O:50][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])=[CH:60][CH:59]=3)=[O:19])=[CH:21][CH:22]=2)[C:23]([O:25][CH3:26])=[O:24])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 431283004-heptoxy-N'-hydroxybenzenecarboximidamideHCID 86689655(S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid

Product 1

HCID 178444059HCID 178444059, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Prepared using General Procedure 5: To a solution of (S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid, INT-1 (10.0 mg, 0.026 mmol) in anhydrous DMF (1 mL) was added HOBt (5.27 mg, 0.39 mmol) and EDC (7.48 mg, 0.39 mmol). After stirring for 2 h, (Z)-4-(heptyloxy)-N′-hydroxybenzimidamide (9.76 mg, 0.39 mmol) was added. The reaction mixture was stirred at RT for 2 h, partitioned between saturated aqueous NaHCO3 (5 ml) and EA (5 mL), and concentrated under reduced pressure to afford the intermediate (S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(((4-(heptyloxy)benzimidamido)oxy)carbonyl)phenyl)propanoate. The intermediate was dissolved in DMF (1 mL) and heated to 100° C. for 18 h. The reaction mixture was cooled to RT and partitioned between EA (5 mL) and saturated aqueous NaHCO3 (5 mL). The organic layer was extracted with water (2×5 mL) and brine (5 mL). The organic layer was dried over MgSO4 and concentrated. The brown oil was purified by preparative HPLC to afford 4.5 mg (29%) of (S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(3-(4-(heptyloxy)phenyl)-1,2,4-oxadiazol-5-yl)phenyl)propanoate. LCMS-ESI (m/z) calculated for C36H43N3O5: 597.3; no m/z observed, tR=12.75 min (Method 2). 1H NMR (400 MHz, DMSO) δ 8.85 (d, J=8.0 Hz, 1H), 8.09 (d, J=8.3 Hz, 2H), 8.00 (d, J=8.9 Hz, 2H), 7.74 (d, J=8.5 Hz, 2H), 7.59 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.6 Hz, 2H), 7.12 (d, J=8.9 Hz, 2H), 4.87-4.56 (m, 1H), 4.06 (t, J=6.5 Hz, 2H), 3.67 (s, 3H), 3.32-3.13 (m, 4H), 1.74 (dd, J=14.2, 6.5 Hz, 2H), 1.51-1.37 (m, 2H), 1.33 (s, 4H), 1.26 (d, J=20.2 Hz, 9H), 0.88 (t, J=6.9 Hz, 3H). 13C NMR (101 MHz, DMSO) δ 175.00, 171.91, 167.89, 166.27, 161.21, 154.37, 143.68, 130.78, 130.30, 128.76, 127.80, 127.18, 125.07, 121.69, 118.21, 115.07, 67.72, 53.61, 52.05, 36.15, 34.60, 31.20, 30.87, 28.54, 28.39, 25.40, 22.02, 13.93.

Workup

  1. customPrepared
  2. stirringThe reaction mixture was stirred at RT for 2 h
  3. custompartitioned between saturated aqueous NaHCO3 (5 ml) and EA (5 mL)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0f88c3bc4f954596b14ccdc541a5dbbe
Source dataset
uspto-grants-2015_11
Patent number
US09187522B2

Reaction notes

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