Dimethylformamide → HCID 66613323, compound

HRID 1404712Notes

Reaction equation

HRID 1404712 reaction equation
C(Cl)(=O)C(Cl)=O.CN(C)C=O.[C:12]([S:31][CH2:32][CH2:33][C:34](O)=[O:35])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(SCCC(Cl)=O)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:62][NH:63][C:64]1[S:65][C:66]([C:69]2[CH:70]=[N:71][CH:72]=[CH:73][CH:74]=2)=[N:67][N:68]=1>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1.ClCCl.C(=O)(O)[O-].[Na+]>[CH3:62][N:63]([C:64]1[S:65][C:66]([C:69]2[CH:70]=[N:71][CH:72]=[CH:73][CH:74]=2)=[N:67][N:68]=1)[C:34](=[O:35])[CH2:33][CH2:32][S:31][C:12]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

10

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 2627673-[(Triphenylmethyl)sulfanyl]propanoic acidHCID 6488196N-methyl-5-(pyridin-3-yl)-1,3,4-thiadiazol-2-amineHCID 860138253-(Tritylthio)propanoyl chloride

Product 1

HCID 66613323HCID 66613323, compoundYield 87%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
23 °C

Procedure

Oxalyl chloride (380 μL, 4.3 mmol, 1.5 equiv) and N,N-dimethylformamide (11 μL, 0.14 mmol, 0.05 equiv) were sequentially added to a stirred suspension of 3-(tritylthio)propanoic acid (1.0 g, 2.9 mmol, 1.0 equiv) in toluene (10 mL) at 23° C. The resulting bubbling white suspension was stirred at 23° C. for 17 h. The reaction mixture was concentrated by rotary evaporation. A portion of the resulting product, 3-(tritylthio)propanoyl chloride (400 mg, 1.1 mmol, 1.1 equiv), was added to a stirred suspension of N-methyl-5-(pyridin-3-yl)-1,3,4-thiadiazol-2-amine (190 mg, 1.0 mmol, 1.0 equiv) and 4-dimethylaminopyridine (150 mg, 1.2 mmol, 1.2 equiv) in dichloromethane (3.0 mL) at 23° C. The resulting yellow solution was stirred at 23° C. for 15 h. The reaction mixture was diluted with a saturated solution of sodium bicarbonate (40 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers were dried (Na2SO4), gravity-filtered, and concentrated by rotary evaporation. The residue was purified by silica gel column chromatography (ethyl acetate) to afford the title compound as a white foam (450 mg, 87%): mp 60-75° C.; IR (KBr thin film) 3438 (w), 3024 (w), 2909 (w), 2742 (w), 2649 (w), 2565 (w), 1701 (s) cm−1; 1H NMR (300 MHz, CDCl3) δ 9.12 (d, J=2 Hz, 1H), 8.67 (dd, J=5, 2 Hz, 1H), 8.25 (dt, J=8, 2 Hz, 1H), 7.18-7.50 (m, 16H), 3.58 (s, 3H), 2.73 (t, J=7 Hz, 2H), 2.34 (t, J=7 Hz, 2H); ESIMS m/z 523 ([M+H]+).

Workup

  1. customThe resulting bubbling white suspension
  2. concentrationThe reaction mixture was concentrated by rotary evaporation
  3. stirringThe resulting yellow solution was stirred at 23° C. for 15 h
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationgravity-filtered
  7. concentrationconcentrated by rotary evaporation
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-713c6ff0ebf746f28f7e4eed1054ee7c
Source dataset
uspto-grants-2014_12
Patent number
US08912338B2

Reaction notes

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