Triethylamine → HCID 178502877, compound

HRID 2189926Notes

Reaction equation

HRID 2189926 reaction equation
[ClH:1].[CH3:2][O:3][N:4]=[C:5]([NH2:7])[NH2:6].[F:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C:16]1[S:20][C:19]([CH2:27][CH2:28]NC#N)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:18]([C:32](=[O:37])[C@@H:33]([O:35][CH3:36])[CH3:34])[N:17]=1.Cl.CON.C(N(CC)CC)C>C(O)C.C(OCC)(=O)C>[ClH:1].[F:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C:16]1[S:20][C:19]([CH2:27][CH2:28][NH:6][C:5]([NH2:7])=[N:4][O:3][CH3:2])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:18]([C:32](=[O:37])[C@@H:33]([O:35][CH3:36])[CH3:34])[N:17]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 521874O-Methylhydroxylamine hydrochloride2×HCID 20250243HCID 20250243, compoundHCID 86639129HCID 86639129, compound

Product 1

HCID 178502877HCID 178502877, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Preparation of 1-(2-(2,5-difluorophenyl)-3-((S)-2-methoxypropanoyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)ethyl)-2-methoxyguanidine hydrochloride: To a solution of crude (2-(5-(2,5-difluorophenyl)-3-((S)-2-methoxypropanoyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)ethyl)cyanamide (31 mg, 0.072 mmol) and methoxyamine hydrochloride (151 mg, 1.80 mol) in ethanol (3 mL) was added triethylamine (182 mg, 1.80 mmol). After heating to 70° C. in a sealed vessel for 16 hours, additional methoxyamine hydrochloride (151 mg, 1.80 mol) and triethylamine (182 mg, 1.80 mmol) was added, and the reaction mixture was heated to 70° C. in a sealed vessel for an additional 24 hours. The mixture was cooled to room temperature and diluted with ethyl acetate. The salts were removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was chromatographed (4% methanol in dichloromethane with 0.5% NH4OH), and the isolated material was treated with excess HCl in MeOH then concentrated to afford the product as a mixture of diastereomers (23 mg, 62% yield). MS APCI (+) m/z 478 (M+1) detected; 1H NMR (400 MHz, CD3OD) δ 7.69-7.64 (m, 2H), 7.50-7.38 (m, 8H), 7.37-7.29 (m, 6H), 4.83-4.78 (m, 2H), 3.80-3.67 (m, 2H), 3.73 (s, 6H), 3.54-3.45 (m, 2H), 3.45-3.33 (m, 2H), 3.39 (s, 3H), 3.31 (s, 3H), 3.04-2.92 (m, 2H), 1.49 (d, 3H, J=7.1 Hz), 1.45 (d, 3H, J=7.1 Hz).

Workup

  1. temperaturethe reaction mixture was heated to 70° C. in a sealed vessel for an additional 24 hours
  2. temperatureThe mixture was cooled to room temperature
  3. customThe salts were removed by filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was chromatographed (4% methanol in dichloromethane with 0.5% NH4OH)
  6. additionthe isolated material was treated with excess HCl in MeOH
  7. concentrationthen concentrated
  8. customto afford the product
  9. additionas a mixture of diastereomers (23 mg, 62% yield)

Sources & evidence

ORD record
ord-c625e2e7e3f1436895154bea6c99ccb6
Source dataset
uspto-grants-2012_12
Patent number
US08324257B2

Reaction notes

Loading…