Dimethylformamide → HCID 67497264, compound

HRID 1628277Notes

Reaction equation

HRID 1628277 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:25])[C@@H:10]([NH:18][CH2:19][C:20]2[N:21]=[CH:22][S:23][CH:24]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:26][C:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[CH:29][N:28]=1.CN(C=O)C.C([O-])([O-])=O.[K+].[K+]>CO.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>[CH3:26][C:27]1[CH:32]=[C:31]([C:2]2[CH:3]=[C:4]([NH:8][C:9](=[O:25])[C@@H:10]([NH:18][CH2:19][C:20]3[N:21]=[CH:22][S:23][CH:24]=3)[CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:5]=[CH:6][CH:7]=2)[CH:30]=[CH:29][N:28]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 41926642-Methylpyridine-4-boronic acidHCID 67496463HCID 67496463, compound

Product 1

HCID 67497264HCID 67497264, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a 5 mL flask was added (S)—N-(3-bromophenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide 39.B (50 mg, 0.12 mmol), 2-methylpyridin-4-yl boronic acid (21 mg, 0.16 mmol, available from Combi-Phos), tetrakis(triphenylphosphine)palladium(0) (28 mg, 0.024 mmol), DMF (0.5 mL) and saturated aqueous K2CO3 (0.5 mL). The reaction mixture was stirred at 100° C. for 2 hours. The mixture was diluted with methanol (3 mL), filtered and purified directly on reverse phase preparative HPLC to afford (2S)—N-(3-(2-methylpyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide 39 (27.2 mg, 53% yield) as a white solid. LCMS ESI (pos.) m/e: 429.1. (M+1). 1H NMR (500 MHz, MeOH-D4) δ ppm 9.12 (d, J=1.96 Hz, 1H), 8.74 (d, J=6.36 Hz, 1H), 8.19 (s, 1H), 8.12 (dd, J=6.36, 1.96 Hz, 1H), 8.11 (t, J=1.71 Hz, 1H), 7.82 (d, J=1.96 Hz, 1H), 7.68-7.75 (m, 1H), 7.58 (t, J=7.83 Hz, 1H), 7.52-7.56 (m, 1H), 7.23-7.37 (m, 5H), 4.53 (d, J=4.65 Hz, 2H), 4.35 (dd, J=9.29, 5.87 Hz, 1H), 3.46 (dd, J=13.45, 5.87 Hz, 1H), 3.28 (dd, J=13.45, 9.29 Hz, 1H), 2.88 (s, 3H).

Workup

  1. filtrationfiltered
  2. custompurified directly on reverse phase preparative HPLC

Sources & evidence

ORD record
ord-f290fd3fb2004076906158182d2eea4f
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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