Sodium Bicarbonate → HCID 178452517, compound

HRID 625592Notes

Reaction equation

HRID 625592 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7](Cl)[N:8]=2)[N:3]=1.[C:13](=[O:16])([OH:15])[O-].[Na+].CC1(C)C(C)(C)OB([C:26]2[CH:27]=[CH:28][C:29]3[N:33]=[C:32]([C@@H:34]4[CH2:39][C@@H:38]5[C@@H:36]([CH2:37]5)[N:35]4[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[NH:31][C:30]=3[CH:47]=2)O1>O1CCOCC1.O.CO.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>[C:43]([O:15][C:13]([N:35]1[C@H:34]([C:32]2[NH:31][C:30]3[CH:47]=[C:26]([C:2]4[N:3]=[C:4]5[C:9](=[CH:10][CH:11]=4)[N:8]=[C:7]([C:27]4[CH:26]=[CH:47][C:30]6[NH:31][C:32]([C@@H:34]7[CH2:39][C@@H:38]8[C@@H:36]([CH2:37]8)[N:35]7[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[N:33][C:29]=6[CH:28]=4)[CH:6]=[CH:5]5)[CH:27]=[CH:28][C:29]=3[N:33]=2)[CH2:39][C@@H:38]2[C@H:36]1[CH2:37]2)=[O:16])([CH3:46])([CH3:44])[CH3:45]

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 6077512,6-Dichloro-1,5-naphthyridineHCID 58498658(1R,3S,5R)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Product 1

HCID 178452517HCID 178452517, compoundYield 19.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (17.4 mg, 0.015 mmol) was added to a solution of 2,6-dichloro-1,5-naphthyridine (30 mg, 0.151 mmol), sodium bicarbonate (38.0 mg, 0.452 mmol) and (1R,3S,5R)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (141 mg, 0.332 mmol) in dioxane (1.0 mL) and H2O (0.2 mL) and the mixture was heated and stirred at 110° C. for 2 h. The reaction was diluted with MeOH, filtered, concentrated and purified by prep HPLC (H2O-MeOH with 10 mM NH4OAc buffer) to yield tert-butyl (1R,3S,5R)-3-(5-(6-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-benzimidazol-6-yl)-1,5-naphthyridin-2-yl)-1H-benzimidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (22.3 mg, 0.030 mmol) as a white solid. LC-MS retention time 2.11 min; m/z 725 [M+H]+. (Column PHENOMENEX® Luna 3.0×50 mm S10. Solvent A=90% water: 10% methanol: 0.1% TFA. Solvent B=10% water: 90% methanol: 0.1% TFA. Flow Rate=4 mL/min. Start % B=0. Final % B=100. Gradient Time=3 min. Wavelength=220).

Workup

  1. temperaturethe mixture was heated
  2. filtrationfiltered
  3. concentrationconcentrated
  4. custompurified by prep HPLC (H2O-MeOH with 10 mM NH4OAc buffer)

Sources & evidence

ORD record
ord-8c42039b281d465c9f439599502776f2
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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