Cesium carbonate → HCID 118159627, compound

HRID 628421Notes

Reaction equation

HRID 628421 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:20]3[N:24]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[N:23]=[CH:22][CH:21]=3)[N:10]([CH2:11][C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:5]2=[CH:4][CH:3]=1.[NH:31]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl>[C:15]([C:14]1[CH:13]=[C:12]([CH:19]=[CH:18][CH:17]=1)[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([N:31]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[NH:32][C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])=[CH:3][CH:4]=2)[CH:8]=[C:9]1[C:20]1[N:24]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[N:23]=[CH:22][CH:21]=1)#[N:16]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 118159480HCID 118159480, compound

Product 1

HCID 118159627HCID 118159627, compound

Reagents, catalysts & solvents 2

HCID 178439015HCID 178439015, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

3-({5-Chloro-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl]-1H-pyrrolo[3,2-b]pyridin-1-yl}methyl)benzonitrile (1.3 g, 3.1 mmol, from Step 2), di-tert-butyl hydrazine-1,2-dicarboxylate (1.4 g, 6.2 mmol, Aldrich) and Cs2CO3 (2.0 g, 6.2 mmol) were combined in toluene (20. mL) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.24 g, 0.31 mmol, Aldrich) was added. The mixture was degassed and heated at 140° C. for 70 minutes. After cooling to room temperature, the mixture was diluted with DCM, filtered, and concentrated. Flash chromatography, eluting with a gradient from 0-60% EtOAc in hexanes, afforded purified product. Yield: (1.2 g, 63%).

Workup

  1. customThe mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe mixture was diluted with DCM
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washFlash chromatography, eluting with a gradient from 0-60% EtOAc in hexanes
  7. customafforded
  8. custompurified product

Sources & evidence

ORD record
ord-c2558f6c84bf4859a94919d45764f4ac
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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