Sodium Carbonate → HCID 178454215, compound

HRID 1424185Notes

Reaction equation

HRID 1424185 reaction equation
Br[C:2]1[CH:42]=[CH:41][C:5]2[NH:6][C:7]([C@@H:9]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:10][C:11](=[O:32])[NH:12][C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:8][C:4]=2[CH:3]=1.[Cl:43][C:44]1[CH:49]=[C:48]([C:50]#[N:51])[CH:47]=[CH:46][C:45]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.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>[Cl:43][C:44]1[CH:49]=[C:48]([C:50]#[N:51])[CH:47]=[CH:46][C:45]=1[C:2]1[CH:42]=[CH:41][C:5]2[NH:6][C:7]([C@@H:9]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:10][C:11](=[O:32])[NH:12][C:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[N:8][C:4]=2[CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 22052059(2-Chloro-4-cyanophenyl)boronic acidHCID 178454214(S)-tert-butyl (1-(5-bromo-1H-benzo[d]imidazol-2-yl)-3-oxo-3-(tritylamino)propyl)carbamate

Product 1

HCID 178454215HCID 178454215, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-tert-butyl (1-(5-bromo-1H-benzo[d]imidazol-2-yl)-3-oxo-3-(tritylamino)propyl)carbamate (Preparation 14, 87 mg, 0.14 mmol), 2-chloro-4-cyanophenylboronic acid (34 mg, 0.19 mmol) and aqueous sodium carbonate solution (2M, 150 μL, 0.30 mmol) in 1,2-dimethoxyethane (0.95 mL) was sparged with argon three times, then tetrakis(triphenylphosphine)palladium(0) (8 mg, 0.007 mmol) was added. The reaction mixture was heated under microwave irradiation at 120° C. for 60 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulphate, and concentrated in vacuo to give the crude product. The residue was purified using silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (45 mg, 48%) as a pale tan solid.

Workup

  1. customwas sparged with argon three times
  2. washwashed with water and brine
  3. dry with materialdried over anhydrous sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThe residue was purified
  7. washeluting with a 0-100% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-04b53b3cde574477bf2da9c85e319ffb
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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