Tetrahydrofuran → 3-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-pentan-3-ol

HRID 2078749Notes

Reaction equation

HRID 2078749 reaction equation
CO[C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[C:10]([C:21]3[C:22]4[S:35][CH:34]=[CH:33][C:23]=4[N:24](C(OC(C)(C)C)=O)[N:25]=3)[N:11]2C(OC(C)(C)C)=O)=[CH:7][CH:6]=1)=[O:4].[CH2:36]([Mg]Br)[CH3:37].O1CC[CH2:42][CH2:41]1>>[NH:24]1[C:23]2[CH:33]=[CH:34][S:35][C:22]=2[C:21]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[CH:7][CH:6]=[C:5]([C:3]([OH:4])([CH2:36][CH3:37])[CH2:41][CH3:42])[CH:13]=3)=[N:25]1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 576373892-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 1-tert-butyl ester 6-methyl ester2×HCID 178418443HCID 178418443, compound2×

Product 1

HCID 1360162413-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-pentan-3-olYield 92%

Procedure

To 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 1-tert-butyl ester 6-methyl ester [250 mg, 0.5 mmol, Intermediate (36)] in tetrahydrofuran (5 mL) was added a 1.0M solution of ethyl magnesium bromide in tetrahydrofuran (2.5 mL, 2.5 mmol) at −45° C. under nitrogen. The mixture was allowed to warm up and stirred at room temperature for 3 hours. An additional 2 mL of 1.0M ethyl magnesium bromide solution was added. The resulting solution was stirred at room temperature overnight. It was then quenched with a mixture of brine and saturated ammonium chloride and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The residue was chromatographed through silica gel (n-heptane/ethyl acetate, 50/50 as eluant) to produce 3-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-pentan-3-ol [137 mg, 92%, Example 70] as a white powder. LC/MS: 326.2 (M+H), RT=3.07 minutes; 1H NMR [300 Mhz, (CD3)2SO]: δ 13.18 (s, 1H), 11.43 (s, 1H), 7.73 (d, J=5.2 Hz, 1H), 7.50 (s, 1H), 7.44 (d, J=8.2 Hz, 1H), 7.18 (d, J=5.2 Hz, 1H), 6.94 (dd, J1=1.1 Hz, J2=8.4 Hz, 1H), 6.56 (d, J=1.5 Hz, 1H), 4.41 (s, 1H), 1.76 (m, 4H), 0.66 (t, j=6.2 Hz, 6H).

Workup

  1. temperatureto warm up
  2. stirringThe resulting solution was stirred at room temperature overnight
  3. customIt was then quenched with a mixture of brine and saturated ammonium chloride
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was chromatographed through silica gel (n-heptane/ethyl acetate, 50/50 as eluant)

Sources & evidence

ORD record
ord-0b7b61f989a54800bb0fb52d01729419
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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