2-Acetoxyisobutyroyl chloride → HCID 59618691, compound

HRID 1691482Notes

Reaction equation

HRID 1691482 reaction equation
[OH:1]/[N:2]=[C:3](\[NH2:38])/[CH2:4][C:5]1[CH:6]=[CH:7][C:8]2[NH:14][C:13]3[N:15]=[C:16]([C:19]([F:22])([F:21])[F:20])[CH:17]=[CH:18][C:12]=3[CH2:11][N:10]([S:23]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[C:9]=2[CH:37]=1.C([O:42][C:43]([CH3:48])([CH3:47])[C:44](Cl)=O)(=O)C>N1C=CC=CC=1>[F:36][C:33]([F:35])([F:34])[O:32][C:29]1[CH:30]=[CH:31][C:26]([S:23]([N:10]2[C:9]3[CH:37]=[C:5]([CH2:4][C:3]4[N:38]=[C:44]([C:43]([OH:42])([CH3:48])[CH3:47])[O:1][N:2]=4)[CH:6]=[CH:7][C:8]=3[NH:14][C:13]3[N:15]=[C:16]([C:19]([F:21])([F:22])[F:20])[CH:17]=[CH:18][C:12]=3[CH2:11]2)(=[O:25])=[O:24])=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 1234962-Acetoxyisobutyroyl chlorideHCID 59618707HCID 59618707, compound

Product 1

HCID 59618691HCID 59618691, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
82 °C

Procedure

To a solution of (1Z)-N′-hydroxy-2-[6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]ethanimidamide (92 mg, 0.163 mmol, the product of Step A) in pyridine was added 2-acetoxyisobutyryl chloride (0.268 g, 1.63 mmol). The resulting mixture was heated at 80-84° C. for 1.5 hr, until LC-MS indicated the reaction was complete, and then the solution was concentrated to remove pyridine. The bright orange residue was dissolved in 5 mL of MeOH and K2CO3 was added. The mixture was stirred for 2 hr at 50° C., then another 0.5 g of K2CO3 was added and the solution was stirred for another 2 hr. The solution was filtered to remove solids and the filtrate was concentrated to remove MeOH. The residue was purified by column chromatography on silica gel, eluting with hexane/ethyl acetate (3:1-2:1) to give the title compound; Mass Spectrum: m/e=630 (M+1).

Workup

  1. concentrationthe solution was concentrated
  2. customto remove pyridine
  3. dissolutionThe bright orange residue was dissolved in 5 mL of MeOH
  4. additionK2CO3 was added
  5. additionanother 0.5 g of K2CO3 was added
  6. stirringthe solution was stirred for another 2 hr
  7. filtrationThe solution was filtered
  8. customto remove solids
  9. concentrationthe filtrate was concentrated
  10. customto remove MeOH
  11. customThe residue was purified by column chromatography on silica gel
  12. washeluting with hexane/ethyl acetate (3:1-2:1)

Sources & evidence

ORD record
ord-fa95de4e6aaf41cf9a0017ad19dd823c
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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