Phthalic Anhydride → HCID 56962925, compound

HRID 1037556Notes

Reaction equation

HRID 1037556 reaction equation
[CH:1]1([C:4]2[C:12]([N:13]([CH2:18][CH2:19][OH:20])[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:11][C:10]3[C:6](=[C:7]([C:28]([NH:30][CH3:31])=[O:29])[N:8]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1.[C:32]1(=[O:42])[O:37][C:35](=[O:36])[C:34]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:33]12>N1C=CC=CC=1>[CH:1]1([C:4]2[C:12]([N:13]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:18][CH2:19][O:20][C:32]([C:33]3[CH:41]=[CH:40][CH:39]=[CH:38][C:34]=3[C:35]([OH:37])=[O:36])=[O:42])=[CH:11][C:10]3[C:6](=[C:7]([C:28](=[O:29])[NH:30][CH3:31])[N:8]([C:21]4[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=4)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6811Phthalic Anhydride3×HCID 56962849HCID 56962849, compound

Product 1

HCID 56962925HCID 56962925, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide (14) (5.00 mg, 0.0112 mmol) in pyridine (0.200 mL) at RT was added phthalic anhydride (8.29 mg, 0.560 mmol). The reaction mixture was heated under microwave irradiation at 100° C. for 15 min. A further portion of phthalic anhydride (8.29 mg, 0.560 mmol) was added and the reaction mixture reheated at 100° C. for 30 min and 110° C. for 30 min. A further portion of phthalic anhydride (16.6 mg, 1.12 mmol) was added and the reaction mixture was heated at 120° C. for 15 min. The reaction mixture was concentrated in vacuo, the residue redissolved in MeOH (1 mL) and purified by preparative LCMS (40-80% ACN in 0.1% aqueous formic acid). 2-[(2-{[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-2H-indazol-6-yl](methylsulfonyl)amino}ethoxy)carbonyl]benzoic acid (15) was isolated as a white solid (4.29 mg, 64%). ESI-MS rniz calculated for [M+H]+: 595.16; found: 594.98; 1H NMR (400 MHz, d4-MeOH) δ 7.85 (s, 1H), 7.75 (brd, J=7.4 Hz, 2H), 7.63-7.58 (m, 2H), 7.53 (ddd, J=19.3, 15.5, 6.6 Hz, 1H), 7.48-7.42 (m, 2H), 7.34 (brs, 1H), 7.33-7.26 (m, 1H), 4.51-4.37 (m, 2H), 4.32-4.23 (m, 1H), 4.11-4.02 (m, 1H), 3.10 (s, 3H), 2.92 (s, 3H), 2.39-2.30 (m, 1H), 1.06-0.94 (m, 3H), 0.66-0.59 (m, 1H).

Workup

  1. temperaturethe reaction mixture was heated at 120° C. for 15 min
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue redissolved in MeOH (1 mL)
  4. custompurified by preparative LCMS (40-80% ACN in 0.1% aqueous formic acid)

Sources & evidence

ORD record
ord-3dbead96b25644bab899c35c4bc7ec16
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

Loading…