Cesium carbonate → HCID 69676416, compound

HRID 919637Notes

Reaction equation

HRID 919637 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[C:4]2[N:12]([S:15]([C:18]3[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=3)(=[O:17])=[O:16])[CH:13]=[CH:14][C:3]=12.[NH2:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:43])[CH2:33][NH:34][C:35]2[CH:40]=[C:39]([Cl:41])[CH:38]=[C:37]([Cl:42])[CH:36]=2)[CH2:27]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:42][C:37]1[CH:36]=[C:35]([NH:34][CH2:33][C:32]([N:28]2[CH2:29][CH2:30][CH2:31][C@@H:26]([NH:25][C:2]3[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[C:4]4[N:12]([S:15]([C:18]5[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=5)(=[O:16])=[O:17])[CH:13]=[CH:14][C:3]=34)[CH2:27]2)=[O:43])[CH:40]=[C:39]([Cl:41])[CH:38]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67517666HCID 67517666, compoundHCID 69676385HCID 69676385, compound

Product 1

HCID 69676416HCID 69676416, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (1.35 g, 3.70 mmol, 1.0 eq), (R)-1-(3-aminopiperidin-1-yl)-2-((3,5-dichlorophenyl)amino)ethanone (1.34 g, 4.44 mmol, 1.2 eq) in PhCH3 (10 mL) was added Pd(OAc)2 (83 mg, 0.370 mmol, 0.1 eq), xantphos (250 mg, 0.43 mmol, 0.15 eq) and Cs2CO3 (2.82 g, 8.64 mmol, 3.0 eq) and the mixture was heated at 100° C. for 16 h. The reaction was cooled to rt, filtered through Celite, and concentrated in vacuo to afford a residue which was purified by silica gel column chromatography (PE/EA=10:1) to give brown solid (451 mg, yield: 21%). 1H NMR (400 MHz, CDCl3) δ: 8.90 (d, 1H), 8.74˜8.73 (m, 1H), 8.01˜7.94 (m, 2H), 7.54˜7.48 (m, 1H), 7.21˜7.19 (m, 2H), 6.75 (d, 1H), 6.69˜6.68 (m, 1H), 6.42˜6.32 (m, 2H), 5.11˜5.10 (m, 1H), 4.42˜4.38 (m, 1H), 3.92˜3.75 (m, 5H), 3.56˜3.52 (m, 2H), 3.23˜3.20 (m, 1H), 3.09˜3.03 (m, 1H), 2.30 (m, 3H), 2.14˜2.10 (m, 1H), 1.86˜1.72 (m, 1H), 1.69˜1.57 (m, 2H). ESI-MS: 630.0 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to rt
  2. filtrationfiltered through Celite
  3. concentrationconcentrated in vacuo
  4. customto afford a residue which
  5. customwas purified by silica gel column chromatography (PE/EA=10:1)

Sources & evidence

ORD record
ord-4cdb5c0762a24177a0af5a4772987869
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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