Cesium carbonate → tert-butyl 4-(N-(3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfamoyl)piperidine-1-carboxylate

HRID 331022Notes

Reaction equation

HRID 331022 reaction equation
[S:1]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)(=[O:4])(=[O:3])[NH2:2].Br[C:19]1[CH:24]=[CH:23][N:22]=[C:21]2[N:25]([CH:39]([CH3:41])[CH3:40])[CH:26]=[C:27]([C:28]3[CH:36]=[C:35]4[C:31]([CH2:32][CH2:33][N:34]4[CH3:37])=[CH:30][C:29]=3[F:38])[C:20]=12.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+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:38][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][C:28]=1[C:27]1[C:20]3[C:21](=[N:22][CH:23]=[CH:24][C:19]=3[NH:2][S:1]([CH:5]3[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10]3)(=[O:4])=[O:3])[N:25]([CH:39]([CH3:40])[CH3:41])[CH:26]=1)[N:34]([CH3:37])[CH2:33][CH2:32]2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 66589106Tert-butyl 4-sulfamoylpiperidine-1-carboxylateHCID 710902434-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 71092026tert-butyl 4-(N-(3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfamoyl)piperidine-1-carboxylateYield 94.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A microwave vial was charged with tert-butyl 4-sulfamoylpiperidine-1-carboxylate (331 mg, 1.252 mmol), 4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridine (D37) (324 mg, 0.834 mmol), Pd2(dba)3 (76 mg, 0.083 mmol), xantphos (97 mg, 0.167 mmol) and cesium carbonate (816 mg, 2.503 mmol). This was suspended in 1,4-dioxane (7 mL) and degassed under nitrogen atmosphere for 10 mins before subjected to microwave heating at 130° C. for 30 mins. The reaction mixture was filtered through celite (washing with ethyl acetate). The filtrate was removed in vacuo to give a residue which was purified using chromatography on silica (eluted with 0-20% ethyl acetate/DCM) to afford the title compound (450 mg). LCMS (A): m/z (M+H)+ 572, C29H38FN5O4S requires 571 (acidic).

Workup

  1. customdegassed under nitrogen atmosphere for 10 mins
  2. filtrationThe reaction mixture was filtered through celite (washing with ethyl acetate)
  3. customThe filtrate was removed in vacuo
  4. customto give a residue which
  5. customwas purified

Sources & evidence

ORD record
ord-3229035352284c2481221cc91194e41e
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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