1,2-Dimethoxyethane → HCID 178502419, compound

HRID 1751407Notes

Reaction equation

HRID 1751407 reaction equation
[O:1]=[C:2]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]1[NH:21][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[S:35][C:34]4[CH:36]=[C:37](B5OC(C)(C)C(C)(C)O5)[CH:38]=[CH:39][C:33]=4[CH:32]=3)=[CH:27][CH:26]=2)=[CH:23][N:24]=1)[C@H:3]([NH:10][C:11](=[O:14])[O:12][CH3:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[C:50]1[N:51]=[C:52]([C@@H:55]2[CH2:59][CH2:58][CH2:57][N:56]2[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[NH:53][CH:54]=1.C(=O)([O-])[O-].[K+].[K+].C(COC)OC>[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.O>[CH3:13][O:12][C:11]([NH:10][C@H:3]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[C:2]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]1[NH:21][C:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[S:35][C:34]4[CH:36]=[C:37]([C:54]5[N:53]=[C:52]([C@@H:55]6[CH2:59][CH2:58][CH2:57][N:56]6[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[NH:51][CH:50]=5)[CH:38]=[CH:39][C:33]=4[CH:32]=3)=[CH:27][CH:26]=2)=[CH:23][N:24]=1)=[O:1])=[O:14]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 56605192tert-Butyl (2S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 86708731methyl (R)-2-oxo-1-phenyl-2-((S)-2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)ethylcarbamate

Product 1

HCID 178502419HCID 178502419, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of methyl (R)-2-oxo-1-phenyl-2-((S)-2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)ethylcarbamate (261 mg, 0.39 mmol), (S)-tert-butyl 2-(4-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (125 mg, 0.39 mmol), and tetrakis(triphenylphosphine) palladium (0) (45 mg, 0.039 mmol), 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (29 mg, 0.039 mmol), potassium carbonate (109 mg, 0.78 mmol), dimethoxyethane (5 mL), and water (1 mL) was heated at 85° C. for 16 hours. The solvent was removed under reduced pressure and the residue was take up in dichloromethane (15 mL) and washed with water (5 mL) and brine (5 mL). The organic phase was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography with eluant of (10% methanol in ethyl acetate) and hexane. The product containing fractions were combined and the solvent was removed under reduced pressure to provide (S)-tert-Butyl 2-(4-(2-(4-(2-((S)-1-((R)-2-(methoxycarbonylamino)-2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)benzo[b]thiophen-6-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (88 mg, 0.011 mmol, 28%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. washwashed with water (5 mL) and brine (5 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. additionThe product containing fractions
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-d91e5d57f5e14c70a2f781697c4ee322
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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