Lithium Chloride → HCID 178519565, compound

HRID 2177600Notes

Reaction equation

HRID 2177600 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][C:17]2[C:20](I)=[N:21][NH:22][C:16]=2[CH2:15]1)=[O:13].ClC1C(C(F)(F)F)=CC=CC=1C([N:37]1CCC2C(I)=N[N:45]([CH:46]3[CH2:51]CCCO3)[C:39]=2[CH2:38]1)=O.C([Sn](CCCC)(CCCC)C1C=NC=CN=1)CCC.[Cl-].[Li+]>O1CCOCC1.O.CCOC(C)=O.[F-].[K+].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>[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][C:17]2=[C:20]([C:39]3[CH:38]=[N:37][CH:51]=[CH:46][N:45]=3)[NH:21][N:22]=[C:16]2[CH2:15]1)=[O:13]

Participants

10

Reactant 4

HCID 433294Lithium ChlorideHCID 27373162-(Tributylstannyl)pyrazineHCID 90409002HCID 90409002, compoundHCID 90409420HCID 90409420, compound

Product 1

HCID 178519565HCID 178519565, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
170 °C

Procedure

To a solution of 6-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-iodo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (Intermediate 57) (47 mg, 0.103 mmol) in 1,4-dioxane (1 mL) was added 2-tributylstannylpyrazine (0.041 mL, 0.124 mmol), lithium chloride (4 mg, 0.103 mmol) and tetrakis(triphenylphosphine)palladium(0) (119 mg, 0.103 mmol). The reaction was allowed to stir overnight at 110° C. and an additional 3 h in a microwave reactor at 170° C. The reaction was diluted with water and EtOAc and 50% potassium fluoride on Celite© (1 g) was added. After stirring for 1 h, the solution was filtered and the layers in the filtrate were separated. The organic layer was concentrated in vacuo and the residue was purified by HPLC (Agilent prep system, Waters XBridge, C18, 5 μm, 30×100 mm column, 5-99% MeOH/20 mM NH4OH over 18 min at 30 mL/min) to give the desired product. (3 mg, 8%). MS (ESI) mass calcd. C18H13ClF3N5O, 407.1. m/z found 408.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.88 (br s, 1H), 8.60-8.50 (m, 2H), 7.82-7.75 (m, 1H), 7.57-7.41 (m, 3H), 5.20-5.13 (m, 0.5H), 4.95-4.87 (m, 0.5H), 4.52 (d, J=15.7 Hz, 0.5H), 4.41 (d, J=15.8 Hz, 0.5H), 4.34-4.27 (m, 0.5H), 4.10-3.97 (m, 0.5H), 3.60-3.53 (m, 1H), 3.16-3.12 (m, 1H), 2.98 (m, 1H).

Workup

  1. additionwas added
  2. stirringAfter stirring for 1 h
  3. filtrationthe solution was filtered
  4. customthe layers in the filtrate were separated
  5. concentrationThe organic layer was concentrated in vacuo
  6. customthe residue was purified by HPLC (Agilent prep system, Waters XBridge, C18, 5 μm, 30×100 mm column, 5-99% MeOH/20 mM NH4OH over 18 min at 30 mL/min)

Sources & evidence

ORD record
ord-71885764873d4c86b75f4843e7d9b1fd
Source dataset
uspto-grants-2015_06
Patent number
US09066946B2

Reaction notes

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