Aniline → 7-Cyano-2-(3-methyl[1,2,4]thiadiazol-5-yl)heptanoic acid phenylamide

HRID 1639574Notes

Reaction equation

HRID 1639574 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(OC(N(C)C)=[N+](C)C)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2N=N1.NC1C=CC=CC=1.[C:32]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH:39]([C:43]1[S:47][N:46]=[C:45]([CH3:48])[N:44]=1)[C:40](O)=[O:41])#[N:33].C(N(CC)CC)C>ClCCl>[C:12]1([NH:8][C:40](=[O:41])[CH:39]([C:43]2[S:47][N:46]=[C:45]([CH3:48])[N:44]=2)[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][C:32]#[N:33])[CH:11]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 593780557-Cyano-2-(3-methyl[1,2,4]thiadiazol-5-yl)heptanoic acid

Product 1

HCID 593780587-Cyano-2-(3-methyl[1,2,4]thiadiazol-5-yl)heptanoic acid phenylamideYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.63 g, 1.64 mmol) and aniline (0.14 g, 1.5 mmol) in dichloromethane (10 mL) was added over 5 min the crude solution of 7-cyano-2-(3-methyl[1,2,4]thiadiazol-5-yl)heptanoic acid (2021052) and triethylamine. The resultant reaction mixture was then stirred at room temperature overnight before being quenched with citric acid (5 g) in water (50 mL) and extracted with dichloromethane (3×50 mL). The combined organic fractions were dried (MgSO4) and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (3:1 hexane/ethyl acetate followed by 1:1 hexane/ethyl acetate) to afford 7-cyano-2-(3-methyl[1,2,4]thiadiazol-5-yl)heptanoic acid phenylamide (2021044) (440 mg, 73% over two steps) as a yellow oil.

Workup

  1. customThe resultant reaction mixture
  2. custombefore being quenched with citric acid (5 g) in water (50 mL)
  3. extractionextracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic fractions were dried (MgSO4)
  5. customthe solvent was removed under reduced pressure
  6. customThe crude product was purified by flash chromatography (3:1 hexane/ethyl acetate followed by 1:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d25733321a6941cf8a02b8219497eeca
Source dataset
uspto-grants-2012_02
Patent number
US08110577B2

Reaction notes

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