Sodium Bicarbonate → (S)-tert-butyl (1-(5-amino-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

HRID 2170386Notes

Reaction equation

HRID 2170386 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4](Br)[C:5]([C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)=[N:6][CH:7]=1.[Cl:27][C:28]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[C:33]2[C:29]=1[C:30]([NH:47][S:48]([CH3:51])(=[O:50])=[O:49])=[N:31][N:32]2[CH3:46].C(=O)(O)[O-].[Na+]>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.O1CCOCC1>[NH2:1][C:2]1[CH:3]=[C:4]([C:34]2[CH:35]=[CH:36][C:28]([Cl:27])=[C:29]3[C:33]=2[N:32]([CH3:46])[N:31]=[C:30]3[NH:47][S:48]([CH3:51])(=[O:49])=[O:50])[C:5]([C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 90281256N-(4-Chloro-1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamideHCID 90290195tert-Butyl (S)-(1-(5-amino-3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

Product 1

HCID 90290153(S)-tert-butyl (1-(5-amino-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

Reagents, catalysts & solvents 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

In a microwave tube were charged with of (S)-tert-butyl (1-(5-amino-3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate (46A, 350 mg, 0.8 mmol), N-(4-chloro-1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide (410 mg, 1.06 mmol) and PdCl2[P(Cy)3]2 (18 mg, 0.025 mmol). To the mixture was added 16 mL of 1,4-dioxane and 4.9 mL of sodium bicarbonate aqueous solution (1M). The system was purged with argon and then the microwave tube was sealed and the reaction mixture was heated up in a heating bath at 150° C. for 1 hour. After cooling to room temperature, the reaction was partitioned between EtOAc and water. The organic layer was separated and washed with brine, then dried over MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with EtOAc/hexanes to afford the title product. MS (m/z): 606.88 [M+H]+.

Workup

  1. customThe system was purged with argon
  2. customthe microwave tube was sealed
  3. temperatureAfter cooling to room temperature
  4. customthe reaction was partitioned between EtOAc and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with EtOAc/hexanes

Sources & evidence

ORD record
ord-ebe9b40151264e89a5bf1418a8464d1f
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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