Potassium Carbonate → HCID 69675123, compound

HRID 1751540Notes

Reaction equation

HRID 1751540 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([C:19]2[NH:23][C:22]([C@@H:24]4[CH2:28][CH2:27][CH2:26][N:25]4[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[N:21][CH:20]=2)[CH:13]=[CH:12]3)O1.Br[C:38]1[CH:43]=[CH:42][C:41]([C:44]2[NH:48][C:47]([C@@H:49]3[CH2:57][C:52]4([O:56][CH2:55][CH2:54][O:53]4)[CH2:51][N:50]3[C:58](=[O:68])[C@@H:59]([NH:63][C:64](=[O:67])[O:65][CH3:66])[CH:60]([CH3:62])[CH3:61])=[N:46][CH:45]=2)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:66][O:65][C:64]([NH:63][C@@H:59]([CH:60]([CH3:62])[CH3:61])[C:58]([N:50]1[C@H:49]([C:47]2[NH:48][C:44]([C:41]3[CH:40]=[CH:39][C:38]([C:9]4[CH:10]=[C:11]5[C:12](=[CH:17][CH:18]=4)[CH:13]=[C:14]([C:19]4[NH:23][C:22]([C@@H:24]6[CH2:28][CH2:27][CH2:26][N:25]6[C:29]([O:31][C:32]([CH3:34])([CH3:35])[CH3:33])=[O:30])=[N:21][CH:20]=4)[CH:15]=[CH:16]5)=[CH:43][CH:42]=3)=[CH:45][N:46]=2)[CH2:57][C:52]2([O:56][CH2:55][CH2:54][O:53]2)[CH2:51]1)=[O:68])=[O:67]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 584986761,1-Dimethylethyl (2S)-2-[5-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthalenyl]-1H-imidazol-2-yl]-1-pyrrolidinecarboxylateHCID 59610362((S)-1-{(S)-8-[4-(4-Bromo-phenyl)-1H-imidazol-2-yl]-1,4-dioxa-7-aza-spiro[4.4]nonane-7-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Product 1

HCID 69675123HCID 69675123, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(S)-tert-butyl 2-(5-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (150 mg, 0.296 mmol) and methyl (S)-1-((S)-8-(5-(4-bromophenyl)-1H-imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-3-methyl-1-oxobutan-2-ylcarbamate (174 mg, 0.355 mmol) were weighed out in a microwave vessel and dissolved in 1,4-dioxane (3 mL), followed by 2M potassium carbonate (444 uL, 0.888 mmol) and Pd(dppf)Cl2 (21 mg, 0.03 mmol). The mixture was sonicated for 2 minutes and then bubbled with nitrogen gas for 3 min to degas. The vessel was sealed and the content was heated in microwave at 110° C. for 30 min. The crude reaction mixture was then diluted with EtOAc and washed twice with brine and saturated NaHCO3 and once with brine again and dried over MgSO4. The crude solution was then filtered and concentrated down. (233 mg, 99%).

Workup

  1. customThe mixture was sonicated for 2 minutes
  2. custombubbled with nitrogen gas for 3 min
  3. customto degas
  4. customThe vessel was sealed
  5. customThe crude reaction mixture
  6. washwashed twice with brine and saturated NaHCO3 and once with brine again
  7. dry with materialdried over MgSO4
  8. filtrationThe crude solution was then filtered
  9. concentrationconcentrated down

Sources & evidence

ORD record
ord-de9e65567cf84a909eb4bae6c95aaa6e
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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