Dimethylformamide → HCID 57898918, compound

HRID 911040Notes

Reaction equation

HRID 911040 reaction equation
Br[C:2]1[C:3]([O:15][C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=2[F:23])=[CH:4][C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.C[Li].C([Li])CCC.CN(C)[CH:33]=[O:34]>O.C1COCC1>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:16]=1[O:15][C:3]1[C:2]([CH:33]=[O:34])=[CH:7][N:6]=[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)[CH:4]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24826754HCID 24826754, compoundHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 57898918HCID 57898918, compoundYield 55.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A flask was charged with 5-bromo-4-(2,6-difluorophenoxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine (Example 128; 1.0 g, 2.51 mmol) and THF (50 mL) and cooled to −78° C. Methyllithium (1.96 ml, 3.14 mmol) was added slowly and the reaction mixture was stirred for 5 minutes. Butyllithium (1.26 ml, 3.14 mmol) was added and the reaction mixture was stirred for 5 minutes. N,N-dimethylformamide (0.551 g, 7.53 mmol) was added and the reaction mixture was stirred for 5 minutes. Water was added and the reaction mixture was extracted with ethyl acetate. The organic layer was dried, filtered, and concentrated. The residue was titurated with a mixture of hexanes, ether, and DCM and filtered to give the title compound (0.480 g, 51.2% yield) as yellow solid. 1H NMR (d6-DMSO) δ 11.48 (s, 1H), 10.23 (s, 1H), 8.73 (s, 1H), 7.48 (m, 3H), 6.68 (s, 1H), 6.53 (bs, 1H), 2.19 (s, 3H).

Workup

  1. stirringthe reaction mixture was stirred for 5 minutes
  2. stirringthe reaction mixture was stirred for 5 minutes
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionThe residue was titurated with a mixture of hexanes, ether, and DCM
  8. filtrationfiltered

Sources & evidence

ORD record
ord-3a8d2fad6505422ba8713c3f518fcfa8
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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