1-Methylimidazole → 3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1H-indazol-6-yl)benzamide

HRID 1410027Notes

Reaction equation

HRID 1410027 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]([OH:23])=O)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH:30]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([NH2:39])[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:36]3[CH:37]=[C:38]4[C:33]([CH:32]=[N:31][NH:30]4)=[CH:34][CH:35]=3)=[O:23])[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 814231H-Indazol-6-amineHCID 665513433-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

Product 1

HCID 665519373-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1H-indazol-6-yl)benzamideYield 28.6%

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-6-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-6-yl)benzamide (30 mg, 28%) as white solid. 1H NMR (300 MHz, DMSO): δ 12.96 (s, 1H), 10.57 (s, 1H), 10.15 (s, 1H), 9.42 (s, 1H), 8.99 (s, 1H), 8.63 (d, 1H, J=8.1 Hz), 8.33 (s, 1H), 8.12 (d, 1H, J=7.8 Hz), 8.03 (s, 1H), 7.87 (s, 1H), 7.76-7.70 (m, 2H), 7.57 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 7.45 (dd, 1H, J1=8.7 Hz, J2=1.5 Hz), 7.01 (d, 1H, J=9.0 Hz), 3.84 (s, 3H), 3.74 (s, 3H). LC-MS: 524 [M+H]+, tR=1.52 min. HPLC: 97.61% at 214 nm, 97.19% at 254 nm, tR=4.75 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-9608bcdd256143bc99279cb292f92a9b
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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