2-Dimethylaminopyridine → Methyl 5-chloro-1-((4-((dimethylamino)methyl)thiazol-2-yl)carbamoyl)spiro[indoline-3,3'-pyrrolidine]-1'-carboxylate

HRID 1411255Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:14][CH2:13][N:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:11]3)[CH2:9][NH:8][C:5]2=[CH:6][CH:7]=1.[CH3:19][N:20]([CH2:22][C:23]1[N:24]=[C:25]([NH2:28])[S:26][CH:27]=1)[CH3:21].[C:29](N1C=CN=C1)(N1C=CN=C1)=[O:30].CN(C1C=CC=CN=1)C>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:14][CH2:13][N:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:11]3)[CH2:9][N:8]([C:29](=[O:30])[NH:28][C:25]3[S:26][CH:27]=[C:23]([CH2:22][N:20]([CH3:21])[CH3:19])[N:24]=3)[C:5]2=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 45 °C

Procedure

The methyl 5-chlorospiro[indoline-3,3′-pyrrolidine]-1′-carboxylate (20 mg, 0.076 mmol) obtained in Step 1 of Example 89 was dissolved in tetrahydrofuran (1.0 mL). Thereafter, the 4-((dimethylamino)methyl)thiazole-2-amine (12 mg, 0.076 mmol) synthesized by a method described in the known methods (International Publication WO2008/086047 etc.) or a method similar thereto, carbonyldiimidazole (24 mg, 0.152 mmol), and dimethylaminopyridine (1.0 mg, 0.008 mmol) were added to the above obtained solution, and the thus obtained mixture was then stirred at 45° C. for 12 hours. Thereafter, the reaction solution was concentrated in vacuo, and the obtained residue was then purified by silica gel column chromatography (chloroform:methanol=10:1) to obtain the captioned compound (12 mg, 34%) in the form of a white solid.

Workup

concentrationThereafter, the reaction solution was concentrated in vacuo
customthe obtained residue was then purified by silica gel column chromatography (chloroform:methanol=10:1)

Sources & evidence

ORD record: ord-986309b8482c457dabb3eccf3f790fae
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921576B2

Reaction notes

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