Sodium Carbonate → 3-(6-((1R*,2S*)-2'-oxospiro[cyclopropane-1,3'-indoline]-2-yl)-1H-indazol-3-yl)benzenesulfonamide

HRID 447559Notes

Reaction equation

HRID 447559 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12]3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[C:33]([S:37]([NH2:40])(=[O:39])=[O:38])[CH:34]=[CH:35][CH:36]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:22]=[C:14]1[C@@:13]2([CH2:12][C@H:11]2[C:7]2[CH:6]=[C:5]3[C:10]([C:2]([C:31]4[CH:32]=[C:33]([S:37]([NH2:40])(=[O:39])=[O:38])[CH:34]=[CH:35][CH:36]=4)=[N:3][NH:4]3)=[CH:9][CH:8]=2)[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[NH:15]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 164142303-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1-sulfonamideHCID 178517040(1R*,2S*)-2-(3-iodo-1H-indazol-6-yl)-spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 674484793-(6-((1R*,2S*)-2'-oxospiro[cyclopropane-1,3'-indoline]-2-yl)-1H-indazol-3-yl)benzenesulfonamideYield 8.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of (1R*,2S*)-2-(3-iodo-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one (80.2 mg, 0.2 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (68.2 mg, 0.24 mmol) in DME (4 mL) was added 1 M Na2CO3 (0.24 mL, 0.24 mmol), followed by Pd(PPh3)2Cl2 (14 mg, 0.02 mmol). The resulting mixture was purged with argon and microwaved 2 h at 120° C. It was diluted with H2O, extracted with EtOAc and dried (Na2SO4). Removal of solvents provided an oil which was triturated with EtOAc/hex then MeOH/CH2Cl2/hex to give the title compound as a white solid (7 mg, 8%). 1H NMR (400 MHz, DMSO-d6) δ 13.41 (s, 1H), 10.63 (s, 1H), 8.41 (s, 1H), 8.19 (d, J=6.8 Hz, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.20 (d, J=8.0 Hz, 1H), 7.69 (t, J=7.6 Hz, 1H), 7.54 (s, 1H), 7.47 (s, 2H, NH2), 7.08 (d, J=8.4 Hz, 1H), 7.00 (t, J=7.2 Hz, 1H), 6.85 (d, J=6.8 Hz, 1H), 6.54 (t, J=7.4 Hz, 1H), 6.05 (d, J=6.4 Hz, 1H), 3.22 (t, J=7.6 Hz, 1H), 2.38-2.30 (m, 1H), 2.05-1.98 (m, 1H); MS ESI 431.1 [M+H]+, calcd for [C23H18N4O3S+H]+ 431.1.

Workup

  1. customThe resulting mixture was purged with argon
  2. custommicrowaved 2 h at 120° C
  3. additionIt was diluted with H2O
  4. extractionextracted with EtOAc
  5. dry with materialdried (Na2SO4)
  6. customRemoval of solvents
  7. customprovided an oil which
  8. customwas triturated with EtOAc/hex

Sources & evidence

ORD record
ord-a2f909a737be4f72bbe237d9a00a4551
Source dataset
uspto-grants-2013_07
Patent number
US08481525B2

Reaction notes

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