Pivaloyl chloride → HCID 68715181, compound

HRID 1913195Notes

Reaction equation

HRID 1913195 reaction equation
Cl.Cl.[NH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:15](=[O:16])[C:14]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][NH:12]2)=[N:9][CH:10]=1.C(N(CC)C(C)C)(C)C.[CH3:32][C:33]([CH3:38])([CH3:37])[C:34]([Cl:36])=[O:35]>ClCCl>[ClH:36].[CH3:32][C:33]([CH3:38])([CH3:37])[C:34]([NH:3][CH2:4][C:5]1[CH:10]=[N:9][C:8]([N:11]2[C:15](=[O:16])[C:14]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:13][NH:12]2)=[CH:7][CH:6]=1)=[O:35]

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 44139914HCID 44139914, compound

Product 1

HCID 68715181HCID 68715181, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

100 mg (0.3 mmol) of the compound from Example 13 are suspended in 3 ml of dichloromethane. 152 mg (1.2 mmol) of N,N-diisopropylethylamine (Hünig base) are added, and the mixture is stirred at RT for 5 min. 43 mg (0.4 mmol) of 2,2-dimethylpropanoyl chloride are then added, and the mixture is stirred at RT for 16 h. The mixture is then concentrated on a rotary evaporator, the residue is taken up in 5 ml of dioxane and 1 ml 1 N aqueous sodium hydroxide solution is added. This mixture is then purified by preparativer HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA to the water). The product-containing fractions are combined and concentrated on a rotary evaporator. The residue is dissolved in 1 N hydrochloric acid, and the solution is lyophilized. The solid is then stirred in tert-butyl methyl ether for 30 min, filtered off and dried under high vacuum.

Workup

  1. stirringthe mixture is stirred at RT for 16 h
  2. concentrationThe mixture is then concentrated on a rotary evaporator
  3. addition1 ml 1 N aqueous sodium hydroxide solution is added
  4. customThis mixture is then purified by preparativer HPLC (RP18 column
  5. additionmobile phase: acetonitrile/water gradient with addition of 0.1% TFA to the water)
  6. concentrationconcentrated on a rotary evaporator
  7. dissolutionThe residue is dissolved in 1 N hydrochloric acid
  8. stirringThe solid is then stirred in tert-butyl methyl ether for 30 min
  9. filtrationfiltered off
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-39f275686cb745a798772074571c8da4
Source dataset
uspto-grants-2013_12
Patent number
US08609698B2

Reaction notes

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