Potassium Carbonate → 5-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

HRID 1776414Notes

Reaction equation

HRID 1776414 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:19]=[C:18]([NH:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[C:17]([OH:27])=[CH:16][N:15]=2)=[N:6]1.[CH3:32][C:33]1([CH3:40])[O:37][CH:36]([CH2:38]Br)[CH2:35][O:34]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:32][C:33]1([CH3:40])[O:37][C@@H:36]([CH2:38][O:27][C:17]2[C:18]([NH:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[N:19][C:14]([C:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[N:5]([CH2:4][C:3]4[CH:28]=[CH:29][CH:30]=[CH:31][C:2]=4[F:1])[N:6]=3)=[N:15][CH:16]=2)[CH2:35][O:34]1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 1697594-(Bromomethyl)-2,2-dimethyl-1,3-dioxolaneHCID 1362713042-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol

Product 1

HCID 867324455-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

200 mg of 2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol (3-3, 0.49 mmol, 1 eq.), 94.6 mg of 2,2-dimethyl-4(R)-4-bromomethyl-1,3-dioxalane (0.49 mmol, 1 eq.) and 134 mg of potassium carbonate (0.97 mmol, 2 eq.) were suspended in 3.7 ml of dry DMF. The reaction mixture was stirred at 50° C. oil bath temperature for 18 hours. 201 mg of potassium carbonate (1.46 mmol, 3 eq.) were added and the mixture was stirred at 90° C. oil bath temperature for further 24 hours. Then the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine, dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to yield 126 mg (0.27 mmol, 44%) of the analytically pure target compound.

Workup

  1. stirringthe mixture was stirred at 90° C. oil bath temperature for further 24 hours
  2. customThen the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over a silicone
  7. filtrationfilter
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography
  10. customto yield 126 mg (0.27 mmol, 44%) of the analytically pure target compound

Sources & evidence

ORD record
ord-1cb3ef4df6a14475adac8d543412bba6
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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