Water → US11220518, Ex. No. I1

HRID 1927013Notes

Reaction equation

HRID 1927013 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:10]3[CH2:16][N:15]([C:17]([N:19]4[CH2:24][C:23]([CH3:26])([CH3:25])[N:22]([CH3:27])[CH2:21][C@@H:20]4[CH3:28])=[O:18])[C:14]([CH3:30])([CH3:29])[C:11]=3[NH:12][N:13]=2)[C:5]([F:31])=[CH:4][N:3]=1.[CH2:32](B1OC(C)(C)C(C)(C)O1)[CH:33]=[CH2:34].C(=O)([O-])[O-].[Cs+].[Cs+].O>[Pd].C1COCC1>[F:31][C:5]1[C:6]([NH:8][C:9]2[C:10]3[CH2:16][N:15]([C:17]([N:19]4[CH2:24][C:23]([CH3:26])([CH3:25])[N:22]([CH3:27])[CH2:21][C@@H:20]4[CH3:28])=[O:18])[C:14]([CH3:30])([CH3:29])[C:11]=3[NH:12][N:13]=2)=[N:7][C:2]([CH2:32][CH2:33][CH3:34])=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27631714,4,5,5-Tetramethyl-2-(prop-2-en-1-yl)-1,3,2-dioxaborolaneHCID 59333930[3-(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-6,6-dimethyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-5-yl]-((S)-2,4,5,5-tetramethyl-piperazin-1-yl)-methanone

Product 1

HCID 25155477US11220518, Ex. No. I1

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a pressure vessel was added [3-(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-6,6-dimethyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-5-yl]-((S)-2,4,5,5-tetramethyl-piperazin-1-yl)-methanone (0.150 g, 0.330 mmol), 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.12 g, 6.66 mmol), cesium carbonate (0.543 g, 1.66 mmol), dichloro[1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.0408 g, 0.0498 mmol), H2O (0.3 mL), and THF (3 mL). The suspension was purged with argon for 2 min, then stirred at 100° C. for 15 h. The cooled solution was filtered to remove undissolved solids and the volatiles removed in vacuo. The residue was redissolved in MeOH (5 mL) and 10% palladium on carbon (0.0400 g, 0.380 mmol) was added. The suspension was evacuated and backfilled with hydrogen for 3 times and allowed to stir for 15 h under hydrogen. The suspension was filtered through Celite, the filter cake washed with CH2Cl2, and the filtrate concentrated. Preparative HPLC provided the desired product I1 as a white solid (0.025 g, 14%).

Workup

  1. customThe suspension was purged with argon for 2 min
  2. filtrationThe cooled solution was filtered
  3. customto remove undissolved solids
  4. customthe volatiles removed in vacuo
  5. dissolutionThe residue was redissolved in MeOH (5 mL)
  6. customThe suspension was evacuated
  7. stirringto stir for 15 h under hydrogen
  8. filtrationThe suspension was filtered through Celite
  9. washthe filter cake washed with CH2Cl2
  10. concentrationthe filtrate concentrated

Sources & evidence

ORD record
ord-3d071a075c9c4b6fae88539f0036774c
Source dataset
uspto-grants-2012_05
Patent number
US08183255B2

Reaction notes

Loading…