Triethylamine → HCID 178502878, compound

HRID 2189954Notes

Reaction equation

HRID 2189954 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[S:13][C:12]([CH2:20][CH2:21][CH2:22][NH:23][C:24]#[N:25])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:11]([C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[N:10]=1.Cl.[CH3:32][O:33][NH2:34].C(N(CC)CC)C>CCO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[S:13][C:12]([CH2:20][CH2:21][CH2:22][NH:23]/[C:24](/[NH2:25])=[N:34]\[O:33][CH3:32])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:11]([C:26](=[O:30])[CH:27]([CH3:28])[CH3:29])[N:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 521874O-Methylhydroxylamine hydrochloride2×HCID 86639140HCID 86639140, compound

Product 1

HCID 178502878HCID 178502878, compoundYield 36.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Crude (3-(5-(2,5-difluorophenyl)-3-isobutyryl-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)propyl)cyanamide (35 mg, 0.08168 mmol) was transferred to a sealed tube in 3 mL of EtOH. Methoxyamine hydrochloride (170.5 mg, 2.042 mmol) and triethylamine (0.2846 ml, 2.042 mmol) were then added and the reaction heated to 70° C. for 18 hours. An additional 50 eq. of methoxyamine hydrochloride was added along with 50 equivalents of TEA. The reaction was then heated for 24 hours. The reaction was concentrated in vacuo, and the salts washed with ethyl acetate. The filtrate was then concentrated in vacuo, and the residue was purified by flash column chromatography (5-10% MeOH/CH2Cl2), to afford the desired product (14.2 mg, 36% yield) as a clear oil. MS ESI (+) m/z 476 (M+E) detected; 1H NMR (400 MHz, CDCl3) δ 7.52 (m, 1H), 7.38 (m, 4H), 7.13 (ms 3H), 3.73 (s, 3H), 3.54 (m, 1H), 3.38 (m, 4H), 2.50 (m, 1H), 2.13 (m, 1H), 1.64 (m, 1H), 1.19 (d, J=7.2 Hz, 6H).

Workup

  1. temperatureThe reaction was then heated for 24 hours
  2. concentrationThe reaction was concentrated in vacuo
  3. washthe salts washed with ethyl acetate
  4. concentrationThe filtrate was then concentrated in vacuo
  5. customthe residue was purified by flash column chromatography (5-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-70aaf16683cd486dbda74a7354be45c1
Source dataset
uspto-grants-2012_12
Patent number
US08324257B2

Reaction notes

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