Cyanoacetic acid → HCID 86720904, compound

HRID 524848Notes

Reaction equation

HRID 524848 reaction equation
Cl.[NH2:2][C:3]1[CH:4]=[N:5][CH:6]=[C:7]([F:24])[C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([C:15]([N:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[O:16])[CH2:11][CH2:10]1.CCN(C(C)C)C(C)C.[C:34]([CH2:36][C:37](O)=[O:38])#[N:35].CCN=C=NCCCN(C)C>C(Cl)Cl>[C:34]([CH2:36][C:37]([NH:2][C:3]1[CH:4]=[N:5][CH:6]=[C:7]([F:24])[C:8]=1[N:9]1[CH2:10][CH2:11][CH:12]([C:15]([N:17]2[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]2)=[O:16])[CH2:13][CH2:14]1)=[O:38])#[N:35]

Participants

6

Reactant 4

HCID 9740Cyanoacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 86720905HCID 86720905, compound

Product 1

HCID 86720904HCID 86720904, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of [1-(3-amino-5-fluoro-4-pyridyl)-4-piperidyl]-(4-methylpiperazin-1-yl)methanone hydrochloride 17b (300 mg, 0.8383 mmol) and DIPEA (541.8 mg, 730.2 μL, 4.192 mmol) in DCM (8 mL) was added cyanoacetic acid 7 (106.9 mg, 1.257 mmol). The reaction mixture was cooled on an ice bath and EDCI (241.0 mg, 1.257 mmol) was then added. The mixture was stirred at room temperature overnight, then heated under reflux for 4 h. The reaction mixture was cooled to room temperature and diluted with DCM (30 mL), washed with water (2×10 ml), then saturated sodium hydrogen carbonate solution (10 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo to afford the desired product 8a as an orange foam (292 mg, 90%). MS (ES+) 389.2.

Workup

  1. temperatureThe reaction mixture was cooled on an ice bath
  2. temperatureheated
  3. temperatureunder reflux for 4 h
  4. temperatureThe reaction mixture was cooled to room temperature
  5. washwashed with water (2×10 ml)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2e184ac102e64deda0da18390e2f973c
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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