Diisopropylethylamine → HCID 178496746, compound

HRID 2189924Notes

Reaction equation

HRID 2189924 reaction equation
[C:1]([N:3]=[C:4](OCC)[CH3:5])#[N:2].Cl.[NH2:10][CH2:11][CH2:12][C:13]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:17]([C:18](=[O:23])[C@@H:19]([O:21][CH3:22])[CH3:20])[N:16]=[C:15]([C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=2[F:31])[S:14]1.C(N(C(C)C)CC)(C)C>CCO.C([O-])([O-])=O.[Na+].[Na+]>[C:1]([N:3]=[C:4]([NH:10][CH2:11][CH2:12][C:13]1([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:17]([C:18](=[O:23])[C@@H:19]([O:21][CH3:22])[CH3:20])[N:16]=[C:15]([C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=2[F:31])[S:14]1)[CH3:5])#[N:2]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 258806Ethyl N-cyanoethanimideateHCID 68548022HCID 68548022, compound

Product 1

HCID 178496746HCID 178496746, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 10340Sodium CarbonateSolvent

Procedure

Preparation of N′-cyano-N-(2-(5-(2,5-difluorophenyl)-3-((S-2-methoxypropanoyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)ethyl)acetamidine: To a solution of ethyl N-cyanoacetimidate (0.025 g, 0.22 mmol) and (2S)—(2-(2-aminoethyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-methoxypropan-1-one hydrochloride (0.018 g, 0.038 mmol) in EtOH (0.3 mL) was added diisopropylethylamine (0.033 mL, 0.19 mmol). After stirring at room temperature for 14 hours, the mixture was diluted with 10% Na2CO3 (30 mL) and extracted with dichloromethane. The combined organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was chromatographed (3% MeOH in dichloromethane) to provide the product as a mixture of diastereomers (13.0 mg, 73% yield). MS ESI (+) m/z 472 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 7.51 (m, 2H), 7.37 (m, 6H), 7.33 (m, 4H), 7.16 (m, 4H), 6.93 (br. t, 1H, J=4.7 Hz), 6.73 (br. t, 1H, J=4.7 Hz), 4.73 (m, 2H), 4.00 (m, 2H), 3.45-3.29 (m, 9H), 3.21 (m, 1H), 2.82 (m, 1H), 2.75 (m, 1H), 2.16 (s, 3H), 2.15 (s, 3H), 1.46 (d, 3H, J=6.3 Hz), 1.43 (d, 3H, J=7.0 Hz).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe combined organics were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed (3% MeOH in dichloromethane)
  6. customto provide the product
  7. additionas a mixture of diastereomers (13.0 mg, 73% yield)

Sources & evidence

ORD record
ord-e78ebaae2a2949ecad9e03ed4086f261
Source dataset
uspto-grants-2012_12
Patent number
US08324257B2

Reaction notes

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