Potassium Phosphate, Tribasic → HCID 67045362, compound

HRID 408187Notes

Reaction equation

HRID 408187 reaction equation
Br[C:2]1[C:3]([N:27]2[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:28]2)=[C:4]2[C:10]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)=[CH:9][N:8]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:5]2=[N:6][CH:7]=1.[CH:41]1(B(O)O)[CH2:43][CH2:42]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:37]([O:36][C:34]([NH:33][C@@H:29]1[CH2:30][CH2:31][CH2:32][N:27]([C:3]2[C:2]([CH:41]3[CH2:43][CH2:42]3)=[CH:7][N:6]=[C:5]3[N:8]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:9]=[C:10]([NH:11][C:12](=[O:19])[C:13]4[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=4)[C:4]=23)[CH2:28]1)=[O:35])([CH3:40])([CH3:39])[CH3:38]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67045305HCID 67045305, compound

Product 1

HCID 67045362HCID 67045362, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22272177Toluene waterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (170 mg, 0.276 mmol), cyclopropylboronic acid (95 mg, 1.10 mmol), K3PO4 (205 mg, 0.967 mmol), Pd(OAc)2 (6.20 mg, 0.0276 mmol), and tricyclohexylphosphine (9.3 mg, 0.033 mmol) in toluene/water (10:1 mixture, 4.4 mL) was degassed under argon and heated at 80° C. for 15 hours. The reaction mixture was then allowed to cool to room temperature. The mixture was poured into water and extracted with CH2Cl2. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 5 to 95% CH3CN/water gradient; 30 CV) to provide (R)-tert-butyl 4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-5-cyclopropyl-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (81 mg, 51% yield). LCMS (APCI+) m/z 577.2 (M+H)+, Retention time=4.01 minutes (Method 2).

Workup

  1. customwas degassed under argon
  2. temperatureto cool to room temperature
  3. additionThe mixture was poured into water
  4. extractionextracted with CH2Cl2
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-67a03c4bdc5d43319929d059fd8c595e
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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