Triethylamine → HCID 178468674, compound

HRID 574679Notes

Reaction equation

HRID 574679 reaction equation
[OH:1][C:2]1[C:7]([NH:8][C:9](=[O:23])[CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:6][N:5]=[C:4]([CH:24]=[N:25][OH:26])[N:3]=1.C1C(=O)N(Cl)C(=O)C1.[C:35]([O:39][CH2:40][CH3:41])(=[O:38])[C:36]#[CH:37].CCN(CC)CC>CN(C=O)C.O>[C:11]1([CH:10]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:9]([NH:8][C:7]2[C:2]([OH:1])=[N:3][C:4]([C:24]3[CH:37]=[C:36]([C:35]([O:39][CH2:40][CH3:41])=[O:38])[O:26][N:25]=3)=[N:5][CH:6]=2)=[O:23])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12182Ethyl propiolateHCID 31398ChlorosuccinimideHCID 178522399HCID 178522399, compound

Product 1

HCID 178468674HCID 178468674, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of step A product, 3-2-a, (0.85 g, 2.4 mmol) in DMF (15 mL), was added NCS (0.42 g, 3.15 mmol) at room temperature. The reaction mixture was heated at 60° C. for 1 h. The reaction mixture was cooled to 0° C. and ethyl propiolate (0.67 g, 6.8 mmol) was added. Then Et3N (0.3 g, 3 mmol) in DMF (5 mL) was added dropwise over 20 min. The reaction mixture was slowly allowed to warm to room temperature and stirred for overnight. The mixture was diluted with water (50 mL) and extracted with EA (100 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuum. The residue was purified by column chromatography with the eluent (PE:EA=2:1) to afford 3-2 (150 mg, 14%) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ10.04 (s, 1H), 8.9 (s, 1H), 7.68 (s, 1H), 7.35-7.26 (m, 11H), 5.76 (s, 1H), 4.40 (q, J=7.2 Hz, 2H), 1.34 (t, J=7.2 Hz, 3H). LC-MS: (M+H)+ 445.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. temperatureto warm to room temperature
  3. extractionextracted with EA (100 mL)
  4. washThe organic layer was washed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuum
  7. customThe residue was purified by column chromatography with the eluent (PE:EA=2:1)

Sources & evidence

ORD record
ord-9fc05a17fade48069a86750984d430b0
Source dataset
uspto-grants-2015_05
Patent number
US09034851B2

Reaction notes

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