2-Bromoethanol → 5-cyclopropyl-2-[4-(4-fluorophenoxy)phenyl]-6-[(2-hydroxyethyl)-(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide

HRID 1037536Notes

Reaction equation

HRID 1037536 reaction equation
[CH:1]1([C:4]2[C:12]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:11][C:10]3[C:6](=[C:7]([C:32]([NH:34][CH3:35])=[O:33])[N:8]([C:18]4[CH:23]=[CH:22][C:21]([O:24][C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)=[CH:20][CH:19]=4)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:43][CH2:44][OH:45]>C(#N)C.CCOC(C)=O>[CH:1]1([C:4]2[C:12]([N:13]([CH2:43][CH2:44][OH:45])[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:11][C:10]3[C:6](=[C:7]([C:32]([NH:34][CH3:35])=[O:33])[N:8]([C:18]4[CH:19]=[CH:20][C:21]([O:24][C:25]5[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=5)=[CH:22][CH:23]=4)[N:9]=3)[CH:5]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 569626885-cyclopropyl-2-[4-(4-fluorophenoxy)phenyl]-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide

Product 1

HCID 569627685-cyclopropyl-2-[4-(4-fluorophenoxy)phenyl]-6-[(2-hydroxyethyl)-(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamideYield 34.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Compound (2) (13 mg, 26 μmol) in ACN (1 mL) was added potassium carbonate (7.3 mg, 52 μmol) followed by 2-bromoethanol (5.6 μL, 79 μmol). The mixture was then stirred at 80° C. for 16 h (monitored by LCMS). The mixture was cooled to RT, diluted with EtOAc (3 mL), washed with water (1 mL) and brine (2 mL). The organic phase was dried (MgSO4) and the solvent was removed in vacuo. The crude mixture was purified by preparative HPLC to give Compound (3) (4.86 mg, 34%) as a white powder. ESI-MS m/z calculated for [M+H]+: 539.18; found: 539.12; 1H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H), 7.52 (brd, J=9.0 Hz, 2H), 7.47 (s, 1H), 7.12-7.02 (m, 6H), 5.79 (brd, J=4.3 Hz, 1H), 4.21-4.00 (m, 1H), 3.85-3.62 (m, 3H), 3.18 (s, 3H), 2.99 (d, J=4.9 Hz, 3H), 2.51-2.27 (m, 1H), 1.06 (ddd, J=11.3, 6.9, 3.1 Hz, 3H), 0.62-0.44 (m, 1H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. washwashed with water (1 mL) and brine (2 mL)
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customthe solvent was removed in vacuo
  5. customThe crude mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-2f8c2be025a14fd8b45a493297dacde3
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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