Benzenesulfonamide → tert-butyl 3-(3-(5-fluoro-1-methylindolin-6-yl)-4-(phenylsulfonamido)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate

HRID 331016Notes

Reaction equation

HRID 331016 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:22]3[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]3)[CH:9]=[C:10]([C:11]3[CH:19]=[C:18]4[C:14]([CH2:15][CH2:16][N:17]4[CH3:20])=[CH:13][C:12]=3[F:21])[C:3]=12.[C:33]1([S:39]([NH2:42])(=[O:41])=[O:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=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+]>O1CCOCC1.C(O[Pd]OC(=O)C)(=O)C.O>[F:21][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][C:11]=1[C:10]1[C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[NH:42][S:39]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)(=[O:41])=[O:40])[N:8]([CH:22]3[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[CH2:23]3)[CH:9]=1)[N:17]([CH3:20])[CH2:16][CH2:15]2

Participants

8

Reactant 4

HCID 7370BenzenesulfonamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 71090156tert-butyl 3-(4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate

Product 1

HCID 86720287tert-butyl 3-(3-(5-fluoro-1-methylindolin-6-yl)-4-(phenylsulfonamido)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylateYield 85.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl 3-(4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate (D32) (420 mg, 0.838 mmol), benzene sulfonamide (158 mg, 1.005 mmol), xantphos (97 mg, 0.168 mmol), diacetoxypalladium (18.81 mg, 0.084 mmol), cesium carbonate (819 mg, 2.51 mmol) in 1,4-dioxane (7 mL) was refluxed at 120° C. for 3 hours. The mixture was cooled. Water (50 mL) was added and extracted with ethyl acetate (3×50 mL). The combined organics were dried over magnesium sulfate, filtered and concentrated to give a residue which was purified on normal phase silica, eluting with ethyl acetate in cyclohexane (0-50%) to give the title compound (413 mg). LCMS (A): m/z (M+H)+ 578, C30H32FN5O4S requires 577 (acidic).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue which
  7. customwas purified on normal phase silica
  8. washeluting with ethyl acetate in cyclohexane (0-50%)

Sources & evidence

ORD record
ord-d9d84ae2130148f489b0069644ef98d7
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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