Sodium Carbonate → HCID 59472333, compound

HRID 2204852Notes

Reaction equation

HRID 2204852 reaction equation
Br[C:2]1[N:3]=[C:4]([C:23]2[O:24][C:25]([C:28]3[S:29][CH:30]=[CH:31][C:32]=3[CH3:33])=[N:26][N:27]=2)[C:5]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.[C:34]([C:36]1[CH:37]=[C:38]([CH:55]=[CH:56][C:57]=1B1OC(C)(C)C(C)(C)O1)[C:39]([N:41]1[CH2:47][CH2:46][CH2:45][N:44]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:43][CH2:42]1)=[O:40])#[N:35].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.O>[C:11]([O:10][C:9]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:5]1[N:6]=[CH:7][C:2]([C:57]2[CH:56]=[CH:55][C:38]([C:39]([N:41]3[CH2:47][CH2:46][CH2:45][N:44]([C:48]([O:50][C:51]([CH3:52])([CH3:54])[CH3:53])=[O:49])[CH2:43][CH2:42]3)=[O:40])=[CH:37][C:36]=2[C:34]#[N:35])=[N:3][C:4]=1[C:23]1[O:24][C:25]([C:28]2[S:29][CH:30]=[CH:31][C:32]=2[CH3:33])=[N:26][N:27]=1)=[O:15])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 59472351HCID 59472351, compoundHCID 67425728HCID 67425728, compound

Product 1

HCID 59472333HCID 59472333, compoundYield 60.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

tert-Butyl N-[5-bromo-3-[5-(3-methyl-2-thienyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (13.52 g, 25.12 mmol) and tert-butyl 4-[3-cyano-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]-1,4-diazepane-1-carboxylate (11.44 g, 25.12 mmol) were taken up in DMF (160 mL) and Na2CO3 (37.68 mL of 2 M, 75.36 mmol) (4:1 mixture) and reaction mixture degassed with nitrogen and Pd (tBu3P)2 (1.027 g, 2.010 mmol) added in one portion. The resulting mixture was heated at 75° C. 2.5 h. The reaction mixture was cooled to room temperature and diluted with EtOAc (50 mL) and water (50 mL). The organic extracts were washed with water (1×100 mL) and brine (1×100 mL) and then the aqueous layers back extracted with ethyl acetate (3×100 mL), dried over MgSO4, filtered and concentrated in vacuo. The material was passed through a silica pad eluting with 50-100% EtOAc/Petroleum ether. The material was purified further by column chromatography on silica (500 mL) eluting with 30-100% EtOAc/petroleum ether. Product fractions were combined and concentrated in vacuo to leave the product as a yellow solid (11.9 g, 55% yield)

Workup

  1. additionadded in one portion
  2. custom2.5 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washThe organic extracts were washed with water (1×100 mL) and brine (1×100 mL)
  5. extractionthe aqueous layers back extracted with ethyl acetate (3×100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. washeluting with 50-100% EtOAc/Petroleum ether
  10. customThe material was purified further by column chromatography on silica (500 mL)
  11. washeluting with 30-100% EtOAc/petroleum ether
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5d516a84f6564c26a324eb56f5963385
Source dataset
uspto-grants-2016_06
Patent number
US09365557B2

Reaction notes

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