Nitrogen → 1-Boc-indole

HRID 2078687Notes

Reaction equation

HRID 2078687 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14]S[C:11]=2[C:10](I)=N1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17](=O)([O-])[O-].[K+].[K+].N#N.O1CC[CH2:27][CH2:26]1>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[C:12]2[C:11](=[CH:10][CH:17]=[CH:14][CH:13]=2)[CH:27]=[CH:26]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 947NitrogenHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 576372991,1-Dimethylethyl 3-iodo-1H-thieno[3,2-c]pyrazole-1-carboxylate

Product 1

HCID 35329801-Boc-indoleYield 69%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
57.5 °C

Procedure

A mixture of 5-(tert-butyl-dimethyl-silanyloxymethyl)-1H-indole-2-boronic acid 1-carboxylic acid tert-butyl ester [3.82 g, 9.42 mmol, Intermediate (8), prepared as described in Example 1-4 of International Patent Application Publication No. WO 02/32861], 3-iodo-thieno[3,2-c]pyrazole-1-carboxylic acid tert-butyl ester [4.0 g, 11.42 mmol, Example 5B above], tetrakis(triphenylphosphine)palladium(0) (544 mg, 0.470 mmol), potassium carbonate (2M aqueous, 12 mL) in tetrahydrofuran (60 mL) is purged with N2 for 10 minutes then heated to 55-60° C. for 7.5 hours. The reaction is diluted with ethyl acetate (50 mL) and washed with water (20 mL). Water layer is back extracted with ethyl acetate (50 mL). The combined ethyl acetate phases are dried over sodium sulfate. The residue is chromatographed on 35 g silica gel cartridge (5-30% ethyl acetate gradient in heptane) to give 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-tert-butyl-dimethyl-silanyloxymethyl)-indole-1-carboxlic acid tert-butyl ester [3.8 g, 69%, Intermediate (9)]; 1H NMR [(CD3)2SO)]: δ 8.08 (2H, m), 7.64 (1H, s), 7.38 (2H, m), 7.14 (1H, s), 4.81 (2H, s, —OCH), 1.65 (9H, s), 1.32 (9H, s), 0.92 (9H, s, Si(CH3)3), 0.10 (6H, s, Si(CH2)); LC/MS: 584 (M+H).

Workup

  1. customprepared
  2. washwashed with water (20 mL)
  3. extractionWater layer is back extracted with ethyl acetate (50 mL)
  4. dry with materialThe combined ethyl acetate phases are dried over sodium sulfate
  5. customThe residue is chromatographed on 35 g silica gel cartridge (5-30% ethyl acetate gradient in heptane)

Sources & evidence

ORD record
ord-f3188e6a250b42d987308ab3300ed689
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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