Water → HCID 86710206, compound

HRID 2168203Notes

Reaction equation

HRID 2168203 reaction equation
Br[C:2]1[C:10]2[C:9]([N:11]3[CH2:16][CH2:15][CH:14]([NH:17][C:18](=[O:25])[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:13][CH2:12]3)=[N:8][CH:7]=[N:6][C:5]=2[N:4]([S:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH:3]=1.[CH3:35][N:36]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[N:37]1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:35][N:36]1[CH2:40][CH:39]([C:2]2[C:10]3[C:9]([N:11]4[CH2:16][CH2:15][CH:14]([NH:17][C:18](=[O:25])[C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH2:13][CH2:12]4)=[N:8][CH:7]=[N:6][C:5]=3[N:4]([S:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)(=[O:28])=[O:27])[CH:3]=2)[CH:38]=[N:37]1

Participants

7

Reactant 4

HCID 962WaterHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 18407952Tripotassium phosphate trihydrateHCID 67988165HCID 67988165, compound

Product 1

HCID 86710206HCID 86710206, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

N-{1-[5-bromo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-4-piperidinyl}benzamide D6 (400 mg), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (185 mg, 0.89 mmol, commercially available from Maybridge, Sigma-Aldrich and Fluorochem), potassium phosphate trihydrate (590 mg, 2.22 mmol), palladium tetrakis (26 mg, 0.022 mmol) were dissolved in 1,4-dioxane (10 ml) and water (2 ml) and stirred under nitrogen at 90° C. overnight. Cooled to room temperature and the solvent removed in vacuo. Water (30 ml) was added and extracted with EtOAc (3×30 ml). The combined extracts were washed with brine and dried over MgSO4, concentrated to give crude product which was purified by silica gel column eluting with EtOAc to give 160 mg of desired product D27. LCMS [MH+] [email protected] min (5 min run)

Workup

  1. customthe solvent removed in vacuo
  2. additionWater (30 ml) was added
  3. extractionextracted with EtOAc (3×30 ml)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto give crude product which
  8. customwas purified by silica gel column
  9. washeluting with EtOAc

Sources & evidence

ORD record
ord-16263562c8c748b390e041b0ddab98b6
Source dataset
uspto-grants-2015_06
Patent number
US09045485B2

Reaction notes

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