Ethyl Acetate → HCID 178502402, compound

HRID 716536Notes

Reaction equation

HRID 716536 reaction equation
Br[C:2]1[C:3]2[S:9][CH:8]=[C:7]([Br:10])[C:4]=2[S:5][CH:6]=1.[CH3:11][O:12][C:13](=[O:46])[NH:14][C@H:15]([C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@H:22]1[C:26]1[NH:27][C:28]([C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)=[CH:29][N:30]=1)=[O:20])[CH:16]([CH3:18])[CH3:17].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>CN(C=O)C.O.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>[CH3:11][O:12][C:13](=[O:46])[NH:14][C@H:15]([C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@H:22]1[C:26]1[NH:30][CH:29]=[C:28]([C:31]2[CH:32]=[CH:33][C:34]([C:2]3[C:3]4[S:9][CH:8]=[C:7]([Br:10])[C:4]=4[S:5][CH:6]=3)=[CH:35][CH:36]=2)[N:27]=1)=[O:20])[CH:16]([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 106139793,6-Dibromothieno(3,2-b)thiopheneHCID 57462153Methyl ((S)-3-methyl-1-oxo-1-((S)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-yl)carbamate

Product 1

HCID 178502402HCID 178502402, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed mixture of 3,6-dibromo-thieno[3,2-b]thiophene (0.335 mmol), compound 8 (0.335 mmol), and sodium carbonate (1.34 mmol) in a mixture of DMF and water (10 mL/1 mL) was added Pd(PPh3)4 (0.335 mmol). The reaction mixture was heated for 1 hr at 80° C. Ethyl acetate and water were then added and the mixture was vigorously stirred for 10 min. The layers were partitioned into a phase separator. The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: DCM to DCM/MeOH 9/1) to give compound A155 as a green gum in 74% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 0.85 (d, J=6.61 Hz, 3H), 0.90 (d, J=6.61 Hz, 3H), 1.92-2.19 (m, 5H), 3.53 (s, 3H), 3.77-3.84 (m, 2H), 4.06 (t, J=8.34 Hz, 1H), 5.07-5.09 (m, 1H), 7.28 (d, J=8.32 Hz, 1H), 7.54 (d, J=1.97 Hz, 1H), 7.70-7.76 (m, 2H), 7.84-7.93 (m, 3H), 8.08-8.14 (m, 1H), 11.81 (s, 1H); MS (ESI, EI+) m/z=587-589 (MH+).

Workup

  1. customThe layers were partitioned into a phase separator
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (eluent: DCM to DCM/MeOH 9/1)
  7. customto give compound A155 as a green gum in 74% yield

Sources & evidence

ORD record
ord-2f822fcd767443d28e1d76119390064d
Source dataset
uspto-grants-2015_11
Patent number
US09187496B2

Reaction notes

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