Nitrogen → 3-(5-acetyl-1-tert-butoxycarbonyl-1H-indol-2-yl)-thieno[3,2-c]pyrazole-1,5-dicarboxylic acid 1-tert-butyl ester 5-methyl ester

HRID 2078698Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](=[O:19])[CH3:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH3:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][O:22][C:23]([C:25]1[S:32][C:31]2C(I)=[N:29][N:28]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:27]=2[CH:26]=1)=[O:24].ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+].C(OC(N1C2C(=CC(CO)=CC=2)C=C1C1C2SC=CC=2N(C(OC(C)(C)C)=O)N=1)=O)(C)(C)C.N#N.S([O-])([O-])(=O)=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH3:21][O:22][C:23]([C:25]1[S:32][C:31]2[C:20]([C:9]3[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:16]4[C:11]([CH:10]=3)=[CH:12][C:13]([C:17](=[O:19])[CH3:18])=[CH:14][CH:15]=4)=[N:29][N:28]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:27]=2[CH:26]=1)=[O:24]

Participants

Conditions

Temperature: 90 °C

Procedure

In a Smith process vial (10-20 mL capacity) is placed 5-acetyl-2-methyl-indole-1-carboxylic acid tert-butyl ester (436 mg, 1.44 mmol, Intermediate (20)], 3-iodo-thieno[3,2-c]pyrazole-1,5-dicarboxylic acid 1-tert-butyl ester 5-methyl ester [392 mg, 0.960 mmol, Intermediate (21)], [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium with dichloromethane adduct (78 mg, 0.0955 mmol), cesium carbonate (938 mg, 2.88 mmol) and a mixture of 1,4-dioxane/water (10:2 mL). The reaction tube is filled with N2 and sealed using capping device. The reaction mixture is heated at 90° C. via microwave (Personal chemistry optimizer) for 10 minutes. Water is pipetted out and added solid sodium sulfate. The organic phase is directly loaded onto 10 g silica gel cartridge and chromatographed on 35 g silica gel cartridge (20-30% ethyl acetate gradient in heptane) to afford 3-(5-acetyl-1-tert-butoxycarbonyl-1H-indol-2-yl)-thieno[3,2-c]pyrazole-1,5-dicarboxylic acid 1-tert-butyl ester 5-methyl ester (230 mg, Example 35) as white solid; 1H NMR [(CD3)2SO)]: δ 8.388 (1H, s), 8.199 (1H), 8.055 (1H), 7.901 (1H, s), 7.339 (1H, s), 3.914 (3H, s), 2.662 (3H, s), 1.671 (9H, s), 1.365 (9H, s); LC/MS: 540 (M+H).

Workup

customsealed
customchromatographed on 35 g silica gel cartridge (20-30% ethyl acetate gradient in heptane)

Sources & evidence

ORD record: ord-82bcfaaf2d924999986dae4c5adeab40
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07928231B2

Reaction notes

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