1,1'-Carbonyldiimidazole → 2-(3-(Trifluoromethyl)-4,5-dihydroindazole-1-yl)acetamido-4,5,6,7-tetrahydrothieno[2,3-c]pyran-3-carboxamide

HRID 1162746

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

2-amino-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxamide (40 mg, 0.20 mmol) and 2-(3-(trifluoromethyl)-4,5,6,7-tetrahydroindazole-1-yl)acetic acid (50 mg, 0.20 mmol) were dissolved in DCM/DMF (3 mL/50 μL) and polymer supported carbonyldiimidazole (330 mg, 1.2 mmol/g, 0.396 mmol) added. The reaction mixture was heated at 120° C. for 10 min in the microwave. The reaction mixture was filtered washing with MeOH (10 mL), EtOAc (10 mL), and MeCN (10 mL). The filtrate was concentrated in vacuo to give a yellow gum. Purification by preparative reverse phase HPLC gave desired product as a white solid (7.6 mg, 0.018 mmol, 9%).

Workup

additionadded
filtrationThe reaction mixture was filtered
washwashing with MeOH (10 mL), EtOAc (10 mL), and MeCN (10 mL)
concentrationThe filtrate was concentrated in vacuo
customto give a yellow gum
customPurification by preparative reverse phase HPLC

Sources & evidence

ORD record: ord-d35ec981d3be486f8f9b94200c0124db
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820707B2

Linked notes

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