Dimethylformamide → HCID 57791824, compound

HRID 1091750Notes

Reaction equation

HRID 1091750 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[O:6]/[C:5]/2=[CH:12]\[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([C:20]([N:22]2[CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24][CH2:23]2)=[O:21])[CH:14]=1.CN(C)C=O.O.[NH2:36][NH2:37]>O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:6])[NH:37][N:36]=[C:5]2[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([C:20]([N:22]2[CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24][CH2:23]2)=[O:21])[CH:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24654Hydrazine hydrate (1:1)HCID 57791857HCID 57791857, compound

Product 1

HCID 57791824HCID 57791824, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
105 °C

Procedure

(Z)-5-chloro-3-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzylidene)isobenzofuran-1 (3H)-one (66) (53 mg, 0.13 mmol) was suspended in water (1.5 mL) and N,N-dimethylformamide (0.5 mL) and treated with Hydrazine monohydrate (35 μl, 0.72 mmol). The resulting mixture was stirred at 105° C. for 1 hour. The reaction mixture was cooled and diluted with water (˜5 mL) and mixture extracted with DCM (2×5 mL). Combined organics were evaporated to dryness to afford the crude product, which was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and acetonitrile as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (13 mg, 24% yield); 1H NMR (400.132 MHz, DMSO) δ 1.28-1.38 (1H, m), 1.40-1.50 (1H, m), 1.49-1.76 (1H, m), 1.83-1.91 (1H, m), 3.01-3.09 (1H, m), 3.25 (3H, s), 3.26-3.37 (2H, m), 3.40-3.46 (1H, m), 3.88-3.96 (1H, m), 4.34 (2H, s), 7.22 (1H, t), 7.35-7.42 (2H, m), 7.87 (1H, dd), 8.02 (1H, d), 8.26 (1H, d), 12.68 (1H, s); m/z (LC-MS, ESI+), RT=2.24 (M+H 430.6).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with DCM (2×5 mL)
  3. customCombined organics were evaporated to dryness
  4. customto afford the crude product, which
  5. customwas purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  6. additionFractions containing the desired compound
  7. customwere evaporated to dryness

Sources & evidence

ORD record
ord-5715227f42604673a8c93e3a84a163de
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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