Potassium Hydroxide → HCID 66823658, compound

HRID 1520741Notes

Reaction equation

HRID 1520741 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18]([NH:20][C:21](=[O:31])[CH2:22]P(=O)(OCC)OCC)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:32][C:33]([N:35]([CH3:37])[CH3:36])=O.[Li+].[Cl-].[OH-].[K+]>O.C(Cl)Cl.CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[F:8])[NH:9][C:10]1[C:11]2[CH:19]=[C:18]([NH:20][C:21](=[O:31])/[CH:22]=[CH:32]/[CH2:33][N:35]([CH3:37])[CH3:36])[N:17]=[CH:16][C:12]=2[N:13]=[CH:14][N:15]=1

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 31374DimethylacetamideHCID 433294Lithium ChlorideHCID 86663604HCID 86663604, compound

Product 1

HCID 66823658HCID 66823658, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of 2,2-diethoxy-N,N-dimethylethanamine (15.7 g, 97.5 mmol) and water (16.4 mL) at room temperature under a nitrogen atmosphere was added aq. 37% HCl (16.4 mL, 195 mmol). After addition the mixture was stirred at 40° C. (bath) for 25 hours. It was then cooled to 0° C. (bath) to give Solution A. KOH (14.0 g, 250 mmol) was dissolved in water (75 mL) at room temperature under a nitrogen atmosphere. It was then cooled to 0° C. (bath) to give Solution B. To a stirred heterogeneous mixture of compound 160 (19.97 g, 39.0 mmol) at room temperature under a nitrogen atmosphere was added a minimum amount of DMA (60 mL) to give a homogeneous solution. LiCl (1.65 g, 39.0 mmol) was then added and the resulting mixture was stirred at 0° C. (bath) for 15 min. The cold Solution B was then added and the reaction was stirred at 0° C. for 2 min. Cold Solution A was then added and the final reaction mixture was stirred further at 0° C. under a nitrogen atmosphere. The reaction was monitored by TLC (DCM/MeOH=10:1). After 30 min more KOH (s) (5.0 g, 89 mmol) was added and the reaction was stirred further at 0° C. for 1.5 hours. It was then poured into water (1,000 mL). Petroleum ether (1,000 mL) was added and the mixture was stirred at room temperature for 20 min. The petroleum ether layer was decanted before more petroleum ether (600 mL) was added and the mixture was again stirred for 15 min. The solid was collected by filtration, washed with water (5×200 mL) and dried under reduced pressure over silica gel/KOH to give (2E)-N-[4-(3-bromo-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]-4-(dimethylamino)-2-butenamide (161) (16.9 g, 97%).

Workup

  1. customto give a homogeneous solution
  2. stirringthe reaction was stirred at 0° C. for 2 min
  3. customthe final reaction mixture
  4. stirringwas stirred further at 0° C. under a nitrogen atmosphere
  5. stirringthe reaction was stirred further at 0° C. for 1.5 hours
  6. stirringthe mixture was stirred at room temperature for 20 min
  7. customThe petroleum ether layer was decanted before more petroleum ether (600 mL)
  8. additionwas added
  9. stirringthe mixture was again stirred for 15 min
  10. filtrationThe solid was collected by filtration
  11. washwashed with water (5×200 mL)
  12. customdried under reduced pressure over silica gel/KOH

Sources & evidence

ORD record
ord-ef146fc3ae3948bfbce2da26081140d4
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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