Tetrahydrofuran → HCID 136016229, compound

HRID 2078750Notes

Reaction equation

HRID 2078750 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][C:34]([CH2:36][O:37][CH2:38][C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)=[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].[CH2:45]([Mg]Br)[CH3:46].O1CC[CH2:51][CH2:50]1>>[CH2:38]([O:37][CH2:36][C:34]1[S:35][C:22]2[C:21]([C:10]3[NH:11][C:12]4[C:8]([CH:9]=3)=[CH:7][CH:6]=[C:5]([C:3]([OH:4])([CH2:45][CH3:46])[CH2:50][CH3:51])[CH:13]=4)=[N:25][NH:24][C:23]=2[CH:33]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 57637358HCID 57637358, compound2×HCID 178418443HCID 178418443, compound2×

Product 1

HCID 136016229HCID 136016229, compoundYield 61%

Conditions

Temperature
-78 °C

Procedure

To 2-(5-benzyloxymethyl-1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 1-tert-butyl ester 6-methyl ester [0.35 g, 0.68 mmol, Intermediate (95)] in tetrahydrofuran (5 mL) at −78° C. under nitrogen was added a 1.0M solution of ethylmagnesium bromide in tetrahydrofuran (1.7 mL, 1.7 mmol). The mixture was stirred at −78° C. for 1 hour. An additional 1.7 mL of 1.0M ethyl magnesium bromide solution was added. The temperature was raised to −45° C. and the mixture was stirred for 1 hour. It was then allowed to warm up to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The residue was chromatographed through silica gel (dichloromethane/ethyl acetate, 50/50 as eluant) to produce 3-[2-(5-benzyloxymethyl-1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-pentan-3-ol [95 mg, 61%, Example 71] as a beige powder. LC/MS: 446.3 (M+H), RT=3.19 minutes. 1H NMR [300 Mhz, (CD3)2SO]: δ 13.18 (s, 1H), 11.44 (s, 1H), 7.50 (s, 1H), 7.45 (s, 1H), 7.43 (d, J=8.3 Hz, 1H), 7.36 (m, 5H), 7.21 (s, 1H), 6.93 (m, 1H), 6.55 (d, J=1.2 Hz, 1H), 4.78 (s, 2H), 4.59 (s, 2H), 4.43 (s, 1H), 1.75 (m, 4H), 0.66 (m, 6H).

Workup

  1. temperatureThe temperature was raised to −45° C.
  2. stirringthe mixture was stirred for 1 hour
  3. temperatureto warm up to room temperature overnight
  4. customThe reaction mixture was quenched with saturated aqueous ammonium chloride
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was chromatographed through silica gel (dichloromethane/ethyl acetate, 50/50 as eluant)

Sources & evidence

ORD record
ord-deac61d39b4d46ca933b725369dc281b
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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