1,2-Dichloroethane → HCID 178444061, compound

HRID 1775804Notes

Reaction equation

HRID 1775804 reaction equation
[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[C:32]([C:36]1[CH:60]=[CH:59][C:39]([C:40]([NH:42][C@@H:43]([CH2:48][C:49]2[CH:54]=[CH:53][C:52](/[C:55](=[N:57]/O)/[NH2:56])=[CH:51][CH:50]=2)[C:44]([O:46][CH3:47])=[O:45])=[O:41])=[CH:38][CH:37]=1)([CH3:35])([CH3:34])[CH3:33]>CN(C=O)C>[C:32]([C:36]1[CH:60]=[CH:59][C:39]([C:40]([NH:42][C@@H:43]([CH2:48][C:49]2[CH:50]=[CH:51][C:52]([C:55](=[NH:56])[NH:57][O:14][C:13](=[O:15])[C:12]3[CH:16]=[CH:17][C:9]([O:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])=[CH:10][CH:11]=3)=[CH:53][CH:54]=2)[C:44]([O:46][CH3:47])=[O:45])=[O:41])=[CH:38][CH:37]=1)([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 85154p-Heptoxybenzoic acidHCID 89620330methyl (2S)-2-[(4-tert-butylbenzoyl)amino]-3-[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]propanoate

Product 1

HCID 178444061HCID 178444061, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Prepared using General Procedure 5: To a solution of 4-(heptyloxy)benzoic acid (400.0 mg, 1.54 mmol) in anhydrous DMF (6 mL) were added HOBt (312.3 mg, 2.31 mmol) and EDC (442.75 mg, 2.31 mmol). After stirring for 2 h, (S,Z)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(N′-hydroxycarbamimidoyl)phenyl)-propanoate, INT-2 (673.3 mg, 1.69 mmol) was added. The reaction mixture was stirred at room temperature for 2 h, partitioned between saturated aqueous NaHCO3 (15 mL) and EA (15 mL), and concentrated under reduced pressure to afford the intermediate (S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(N-((4-(heptyloxy)benzoyl)oxy)carbamimidoyl)phenyl)propanoate. The intermediate was dissolved in DMF (10 mL) and heated to 100° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EA (10 mL) and saturated aqueous NaHCO3 (50 mL). The organic layer was extracted with water (2×10 mL) and brine (10 mL). The organic layer was dried over MgSO4 and concentrated. The brown oil was purified by chromatography (EA/hexanes) to afford 710 mg (77%) of (S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)-1,2,4-oxadiazol-3-yl)phenyl)propanoate as a white solid. LCMS-ESI (m/z) calculated for C36H43N3O5: 597.3; no m/z observed, tR=12.80 min (Method 2). 1H NMR (400 MHz, DMSO) δ 8.84 (d, J=8.0 Hz, 1H), 8.08 (t, J=17.2 Hz, 2H), 7.97 (dd, J=18.2, 8.5 Hz, 2H), 7.74 (d, J=8.5 Hz, 2H), 7.50 (dd, J=18.6, 8.3 Hz, 4H), 7.18 (d, J=8.9 Hz, 2H), 4.85-4.63 (m, 1H), 4.09 (dd, J=13.8, 7.3 Hz, 2H), 3.67 (s, 3H), 3.24 (ddd, J=23.8, 15.7, 7.3 Hz, 4H), 2.08 (s, 4H), 1.74 (dd, J=14.1, 6.9 Hz, 2H), 1.42 (dd, J=13.6, 6.3 Hz, 2H), 1.30 (d, J=14.5 Hz, 9H), 0.88 (t, J=6.8 Hz, 3H). 13C NMR (101 MHz, DMSO) δ 174.05, 170.87, 133.81, 165.14, 161.43, 153.21, 140.51, 129.70, 128.85, 128.78, 126.06, 125.84, 123.93, 123.39, 114.36, 114.25, 66.86, 52.66, 50.88, 34.32, 33.47, 30.06, 29.74, 27.33, 27.24, 24.23, 20.89, 12.80.

Workup

  1. customPrepared
  2. stirringThe reaction mixture was stirred at room temperature for 2 h
  3. custompartitioned between saturated aqueous NaHCO3 (15 mL) and EA (15 mL)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c56fbcd1783645c79dcae1cb1e32a637
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

Loading…