1,2-Dimethoxyethane → HCID 67682236, compound

HRID 1751582Notes

Reaction equation

HRID 1751582 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:22]=[C:21]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:23]5[CH:24]=[CH:25][C:26]6[N:30]=[C:29]([C@@H:31]7[CH2:35][CH2:34][CH2:33][N:32]7[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[NH:28][C:27]=6[CH:43]=5)=[CH:17][C:18]=4[CH2:19][CH2:20]3)=[CH:11][CH:10]=2)O1.Br[C:46]1[NH:50][C:49]([C@@H:51]2[CH2:55][CH2:54][CH2:53][N:52]2[C:56](=[O:66])[C@@H:57]([NH:61][C:62](=[O:65])[O:63][CH3:64])[CH:58]([CH3:60])[CH3:59])=[N:48][CH:47]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(COC)OC>C(OCC)(=O)C.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].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>[CH3:64][O:63][C:62]([NH:61][C@@H:57]([CH:58]([CH3:60])[CH3:59])[C:56]([N:52]1[CH2:53][CH2:54][CH2:55][C@H:51]1[C:49]1[NH:50][C:46]([C:9]2[CH:22]=[C:21]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:23]5[CH:24]=[CH:25][C:26]6[N:30]=[C:29]([C@@H:31]7[CH2:35][CH2:34][CH2:33][N:32]7[C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[NH:28][C:27]=6[CH:43]=5)=[CH:17][C:18]=4[CH2:19][CH2:20]3)=[CH:11][CH:10]=2)=[CH:47][N:48]=1)=[O:66])=[O:65]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 56605304methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamateHCID 67682289(S)-tert-butyl 2-(6-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 67682236HCID 67682236, compoundYield 4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-tert-butyl 2-(6-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (590 mg, 1.0 mmol), methyl (S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (492 mg, 1.3 mmol), PdCl2(dppf) (37 mg, 0.05 mmol), 2M aqueous potassium phosphate solution (1.5 mL, 3.0 mmol), and dimethoxyethane (5 mL) was degassed with a stream of argon for twenty minutes. The reaction was heated to 90° C. After one hour, the reaction was cooled to room temperature and tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) was added. The reaction was heated to 90° C. After three hours, the reaction was cooled to room temperature and more PdCl2(dppf) (37 mg, 0.05 mmol) was added. The reaction was heated to 80° C. After 16 hours, the reaction was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water and brine, dried (Na2SO4) and concentrated. The resulting residue was purified by flash column chromatography to yield (S)-tert-butyl 2-(6-(7-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (30 mg, 4%).

Workup

  1. customwas degassed with a stream of argon for twenty minutes
  2. temperaturethe reaction was cooled to room temperature
  3. temperatureThe reaction was heated to 90° C
  4. waitAfter three hours
  5. temperaturethe reaction was cooled to room temperature
  6. temperatureThe reaction was heated to 80° C
  7. waitAfter 16 hours
  8. temperaturethe reaction was cooled to room temperature
  9. washThe organic phase was washed with water and brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-38f28ced86334bc28945a2ee79b66357
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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