2,6-Lutidine → HCID 178461823, compound

HRID 1818738Notes

Reaction equation

HRID 1818738 reaction equation
[F:1][C:2]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:3]=1[O:4][C:5]1[N:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=2[F:19])[C:8]([CH:20]([N:22]=[C:23]([CH3:29])[CH2:24][S:25]([CH3:28])(=[O:27])=[O:26])Cl)=[CH:7][N:6]=1.[C:35]([O:39]C(OC(C)(C)C)=O)(=[O:38])[NH:36][NH2:37].N1[C:52]([CH3:53])=[CH:51]C=CC=1C.O1CCC[CH2:56]1>>[C:52]([O:39][C:35]([NH:36][N:37]=[C:20]([C:8]1[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=2[F:19])=[N:10][C:5]([O:4][C:3]2[CH:30]=[CH:31][C:32]([F:34])=[CH:33][C:2]=2[F:1])=[N:6][CH:7]=1)[NH:22][C@H:23]([CH3:29])[CH2:24][S:25]([CH3:28])(=[O:27])=[O:26])=[O:38])([CH3:51])([CH3:53])[CH3:56]

Participants

5

Reactant 4

HCID 79372,6-LutidineHCID 8028TetrahydrofuranHCID 86611175HCID 86611175, compoundHCID 86611176HCID 86611176, compound

Product 1

HCID 178461823HCID 178461823, compound

Conditions

Temperature
25 °C

Procedure

The solution of {[2,4-bis-(2,4-difluoro-phenoxy)-pyrimidin-5-yl]-chloro-methyl}-(2-methanesulfonyl-1-methyl-ethylidene)-amine was added to a solution of BOC carbazate (766 g) and 2,6-lutidine (930 g) in tetrahydrofuran (2.0 liters) at 5° C. The reaction mixture was stirred at 25° C. for 24 hours. The reaction mixture was quenched with water (3.0 liters) diluted with methylene chloride (2.0 liters) and the reaction pH was adjusted to pH 3 by addition of 4N HCl (2.4 liters). The layers were separated and the organic layer was washed with saturated sodium bicarbonate (2.0 liters) and a 1:1 mixture of water and saturated brine. The organic layer was concentrated under reduced pressure for 12 hours to give N′-[[2,4-bis-(2,4-difluoro-phenoxy)-pyrimidin-5-yl]-((R)-2-methanesulfonyl-1-methyl-ethylamino)-methylene]-hydrazinecarboxylic acid tert-butyl ester (2.0 kg, quantitative) as a pale yellow powder.

Workup

  1. customThe reaction mixture was quenched with water (3.0 liters)
  2. additiondiluted with methylene chloride (2.0 liters)
  3. additionthe reaction pH was adjusted to pH 3 by addition of 4N HCl (2.4 liters)
  4. customThe layers were separated
  5. washthe organic layer was washed with saturated sodium bicarbonate (2.0 liters)
  6. additiona 1:1 mixture of water and saturated brine
  7. concentrationThe organic layer was concentrated under reduced pressure for 12 hours

Sources & evidence

ORD record
ord-c5853b0849134593b5869994306cba78
Source dataset
uspto-grants-2009_10
Patent number
US07601726B2

Reaction notes

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