Triethylamine → HCID 178502881, compound

HRID 2189932Notes

Reaction equation

HRID 2189932 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C@:5]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]([C:10](=[O:15])[C@@H:11]([O:13][CH3:14])[CH3:12])[N:8]=[C:7]([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[F:23])[S:6]1.[N:30]#[C:31]Br.C(N(CC)CC)C.[ClH:40].[CH3:41][O:42][NH2:43]>ClCCl>[ClH:40].[F:23][C:17]1[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=1[C:7]1[S:6][C@@:5]([CH2:4][CH2:3][CH2:2][NH:1][C:31]([NH2:30])=[N:43][O:42][CH3:41])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:9]([C:10](=[O:15])[C@@H:11]([O:13][CH3:14])[CH3:12])[N:8]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 10476Cyanogen BromideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 60139827HCID 60139827, compound

Product 1

HCID 178502881HCID 178502881, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-1-((S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-methoxypropan-1-one (Example 5, Steps A-C, 52.1 mg, 0.106 mmol) and cyanogen bromide (13.4 mg, 0.127 mmol) in dichloromethane (1 mL) was slowly added triethylamine (35.3 mg, 0.349 mmol). After stirring for 20 minutes at room temperature, the mixture was concentrated under reduced pressure and dissolved in ethanol (2 mL). To this solution was added methoxyamine hydrochloride (600 mg, 7.18 mmol) and triethylamine (642 mg, 6.35 mmol). The reaction vessel was sealed and heated to 70° C. for 24 hours. The mixture was concentrated under reduced pressure and dissolved in ethyl acetate. The precipitate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was chromatographed (3% 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 white solid (7.3 mg, 13% yield). MS APCI (+) m/z 492 (M+1) detected; 1H NMR (400 MHz, CD3OD) δ 7.65-7.60 (m, 1H), 7.47-7.45 (m, 2H), 7.42-7.37 (m, 2H), 7.35-7.29 (m, 3H), 4.79 (q, 1H, J=7.0 Hz), 3.73 (s, 3H), 3.45-3.37 (m, 2H), 3.36 (s, 3H), 3.28-3.19 (m, 1H), 2.60-2.51 (m, 1H), 2.19-2.08 (m, 1H), 1.71-1.60 (m, 1H), 1.43 (d, 3H, J=7.0 Hz).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. dissolutiondissolved in ethanol (2 mL)
  3. customThe reaction vessel was sealed
  4. temperatureheated to 70° C. for 24 hours
  5. concentrationThe mixture was concentrated under reduced pressure
  6. dissolutiondissolved in ethyl acetate
  7. customThe precipitate was removed by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was chromatographed (3% methanol in dichloromethane with 0.5% NH4OH)
  10. additionthe isolated material was treated with excess HCl in MeOH
  11. concentrationthen concentrated

Sources & evidence

ORD record
ord-f0acef98ede34f1d9dd2ffd8effd7717
Source dataset
uspto-grants-2012_12
Patent number
US08324257B2

Reaction notes

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