1,2-Dichloroethane → HCID 72483009, compound

HRID 2261893Notes

Reaction equation

HRID 2261893 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([C:18]1[O:22][C:21]([C:23]2[CH:24]=[C:25]([CH:29]=[C:30]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[CH:31]=2)[C:26](O)=[O:27])=[N:20][N:19]=1)([CH3:17])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:38](N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=N[C:54]2[N:57]([OH:60])N=NC=2C=1>C(Cl)(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([C:18]1[O:22][C:21]([C:23]2[CH:31]=[C:30]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[CH:29]=[C:25]([C:26]([N:57]([O:60][CH3:38])[CH3:54])=[O:27])[CH:24]=2)=[N:20][N:19]=1)([CH3:17])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 68707669HCID 68707669, compound2×

Product 1

HCID 72483009HCID 72483009, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a slurry of 3-(5-{1-[(tert-butoxycarbonyl)amino]-1-methyl-2-phenylethyl}-1,3,4-oxadiazol-2-yl)-5-[methyl(methylsulfonyl)amino]benzoic acid (Intermediate VI) (0.303 g, 0.571 mmol) and Weinreb amine hydrochloride (0.111 g, 1.142 mmol) in 6 mL CHCl3 was added diisopropylethylamine (0.150 mL, 0.857 mmol), followed by EDC (0.154 g, 0.857 mmol) and HOAt (0.035 g, 0.228 mmol) After 7 days at rt, the reaction was quenched by the addition of brine. The layers were separated, the aqueous washed with CH2Cl2 (2×), the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Purification with normal phase chromatography (40->100% EA/hex) afforded tert-butyl[1-(5-{3-{[methoxy(methyl)amino]carbonyl}-5-[methyl(methylsulfonyl)amino]phenyl}-1,3,4-oxadiazol-2-yl)-1-methyl-2-phenylethyl]carbamate as a white foam. 1H NMR (CDCl3, 400 MHz) 8.21 (app t, J=1.5 Hz, 1H), 8.11 (app t, J=2.0 Hz, 1H), 7.90 (app t, J=1.5 Hz, 1H), 7.30-7.22 (m, 3H), 7.06-7.04 (m, 2H), 5.04 (br s, 1H), 3.60 (s, 3H), 3.42 (s, 3H), 3.39 (s, 3H), 2.90 (s, 3H), 1.69 (s, 3H), 1.41 (s, 9H). LCMS [M+H]+=574.

Workup

  1. customthe reaction was quenched by the addition of brine
  2. customThe layers were separated
  3. washthe aqueous washed with CH2Cl2 (2×)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification with normal phase chromatography (40->100% EA/hex)

Sources & evidence

ORD record
ord-d5cbe85f360545a2be5784e37ec6ac95
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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