Hydrochloric Acid → HCID 178502286, compound

HRID 1504318Notes

Reaction equation

HRID 1504318 reaction equation
[CH3:1][O:2][C:3](=[O:32])[NH:4][C@H:5]([C:9]([N:11]1[C@H:19]([C:20]2[NH:21][CH:22]=[C:23]([C:25]3[CH:30]=[CH:29][C:28](Br)=[CH:27][CH:26]=3)[N:24]=2)[CH2:18][C:13]2([O:17][CH2:16][CH2:15][O:14]2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].B([C:36]1[CH:44]=[CH:43][C:39]([C:40]([OH:42])=[O:41])=[CH:38][CH:37]=1)(O)O.C(=O)([O-])[O-].[Na+].[Na+].Cl>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]([NH:4][C@@H:5]([CH:6]([CH3:8])[CH3:7])[C:9]([N:11]1[C@H:19]([C:20]2[NH:21][CH:22]=[C:23]([C:25]3[CH:30]=[CH:29][C:28]([C:36]4[CH:44]=[CH:43][C:39]([C:40]([OH:42])=[O:41])=[CH:38][CH:37]=4)=[CH:27][CH:26]=3)[N:24]=2)[CH2:18][C:13]2([O:17][CH2:16][CH2:15][O:14]2)[CH2:12]1)=[O:10])=[O:32]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 178502285HCID 178502285, compound

Product 1

HCID 178502286HCID 178502286, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of ((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 (450 mg, 0.89 mmol) in dioxane (8 mL) and water (4 mL) was added 4-boronobenzoic acid (154 mg, 0.93 mmol), sodium carbonate (189 mg, 1.78 mmol), and tetrakis(triphenylphosphine)-palladium(0) (104 mg, 0.09 mmol) and the reaction mixture was stirred at reflux for 3 h under nitrogen. The pH was adjusted to 1 with 2 M HCl, and the reaction mixture was extracted with EtOAc (3×20 mL). The organic layers were combined, dried over sodium sulfate, concentrated and purified by flash chromatography (eluted with methanol in DCM, 0 to 7%) to provide the title intermediate as a yellow solid (330 mg, 68% yield). (m/z): [M+H]+ calcd for C29H32N4O7 549.23. found 549.3. 1H NMR (CH3OD, 400) δ (ppm) 8.13-8.11 (m, 2H), 7.90-7.78 (m, 7H), 5.39-5.34 (m, 1H), 4.19-3.91 (m, 7H), 3.66 (s, 3H), 2.72-2.65 (m, 1H), 2.48-2.41 (m, 1H), 2.12-1.95 (m, 1H), 0.92-0.85 (m, 6H).

Workup

  1. temperatureat reflux for 3 h under nitrogen
  2. extractionthe reaction mixture was extracted with EtOAc (3×20 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by flash chromatography (eluted with methanol in DCM, 0 to 7%)

Sources & evidence

ORD record
ord-2e2d1d2ae73c464daabc6d0b33abde9a
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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