1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 67209483, compound

HRID 1465509Notes

Reaction equation

HRID 1465509 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]3[CH:16]=[C:15]([C:17]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=4)([O:19][CH2:20][O:21][CH3:22])[CH3:18])[N:14]=[C:13]([NH2:30])[N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1>CN(C=O)C>[F:29][C:25]1[CH:24]=[C:23]([C:17]([C:15]2[CH:16]=[C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:35]5[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=5)[N:3]=4)[NH:8][CH:9]=3)[N:12]=[C:13]([NH2:30])[N:14]=2)([O:19][CH2:20][O:21][CH3:22])[CH3:18])[CH:28]=[CH:27][CH:26]=1

Participants

4

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 53259485HCID 53259485, compound

Product 1

HCID 67209483HCID 67209483, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

4-(2-Bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-6-[1-(3-fluorophenyl)-1-methoxymethoxyethyl]pyrimidin-2-ylamine (0.249 g, 0.395 mmol) is dissolved in DMF (7 ml), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.164 g, 0.790 mmol) and Pd[PPh3]4 (0.046 mg, 0.040 mmol) are added, the reaction solution is flushed with nitrogen for 5 min, 2N Na2CO3 solution (1.5 ml) is subsequently added. The mixture is stirred at 130° C. for 1 h. The mixture is cooled to room temperature, ethyl acetate is added, and the organic phase is extracted three times with water, the aqueous phase is separated off, and the organic phase is dried over sodium sulfate. The solid is filtered off, and the residue is evaporated in vacuo. The residue is purified by RP-HPLC, giving 4-[1-(3-fluorophenyl)-1-methoxymethoxyethyl]-6-[2-(1-methyl-1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]pyrimidin-2-ylamine (“A2”), (HPLC/MS Rt=1.72 min, [M+H] 475); 1H-NMR [DMSO-d6]: δ [ppm]=12.72 (br, 1H), 8.72 (s, 1H), 8.49 (m, 1H), 8.33 (s, 1H), 8.31 (s, 1H), 8.11 (s, 1H), 7.43 (m, 1H), 7.32 (m, 2H), 7.13 (m, 1H), 4.79 (s, 2H), 3.95 (s, 3H), 3.37 (s, 3H), 1.98 (s, 3H);

Workup

  1. customthe reaction solution is flushed with nitrogen for 5 min
  2. addition2N Na2CO3 solution (1.5 ml) is subsequently added
  3. temperatureThe mixture is cooled to room temperature
  4. additionethyl acetate is added
  5. extractionthe organic phase is extracted three times with water
  6. customthe aqueous phase is separated off
  7. dry with materialthe organic phase is dried over sodium sulfate
  8. filtrationThe solid is filtered off
  9. customthe residue is evaporated in vacuo
  10. customThe residue is purified by RP-HPLC

Sources & evidence

ORD record
ord-5ce62d35cd514e8895b1045bfe087865
Source dataset
uspto-grants-2015_04
Patent number
US08999986B2

Reaction notes

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