1-Methylimidazole → 3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1H-indazol-5-yl)benzamide

HRID 1410026Notes

Reaction equation

HRID 1410026 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21](O)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH:30]1[C:38]2[C:33](=[CH:34][C:35]([NH2:39])=[CH:36][CH:37]=2)[CH:32]=[N:31]1.CCN=C=NCCCN(C)C.CN1C=CN=C1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21]([NH:39][C:35]3[CH:34]=[C:33]4[C:38](=[CH:37][CH:36]=3)[NH:30][N:31]=[CH:32]4)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 880121H-Indazol-5-amineHCID 665513433-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

Product 1

HCID 665519363-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1H-indazol-5-yl)benzamideYield 19.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (82 mg, 0.2 mmol) and 1H-indazol-5-amine (27 mg, 0.2 mmol) in 5 mL of DCM was added EDCI (80 mg, 0.6 mmol) followed by N-methylimidazole (50 mg, 0.6 mmol). The mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with EtOAc to give 3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1H-indazol-5-yl)benzamide (20 mg, 19%) as white solid. 1H NMR (300 MHz, DMSO): δ 13.01 (s, 1H), 10.46 (s, 1H), 10.14 (s, 1H), 9.42 (s, 1H), 8.99 (s, 1H), 8.62 (d, 1H, J=7.8 Hz), 8.29 (s, 1H), 8.13-8.10 (m, 2H), 7.88 (s, 1H), 7.74-7.69 (m, 2H), 7.58-7.55 (m, 2H), 7.01 (d, 1H, J=8.7 Hz), 3.84 (s, 3H), 3.75 (s, 3H). LC-MS: 524 [M+H]+, tR=1.50 min. HPLC: 95.85% at 214 nm, 95.63% at 254 nm, tR=4.60 min.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was purified by column chromatography on silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-13dfd39298e647129dc2cfe1f2c8fbd4
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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