HCID 135499784, compound → HCID 136016230, compound

HRID 2111175Notes

Reaction equation

HRID 2111175 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][S:8][C:4]=2[C:3]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[CH:15][C:14]([C:18](=[O:21])[CH2:19][CH3:20])=[CH:13][CH:12]=3)=[N:2]1.[N:22]1([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[Mg]Br)[CH2:26][CH2:25][CH2:24][CH2:23]1>O1CCCC1>[N:22]1([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:18]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[NH:10][C:9]([C:3]2[C:4]4[S:8][CH:7]=[CH:6][C:5]=4[NH:1][N:2]=2)=[CH:17]3)([OH:21])[CH2:19][CH3:20])[CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

4

Reactant 2

HCID 135499784HCID 135499784, compoundHCID 178419623HCID 178419623, compound

Product 1

HCID 136016230HCID 136016230, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To cooled (−40° C.) solution of 1-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl)-propan-1-one (110 mg, 0.372 mmol, Example 28) in anhydrous tetrahydrofuran (2 mL) is added (2-(1-pyrrolidinylmethyl)phenyl)magnesium bromide (0.25 M in tetrahydrofuran) under nitrogen. After 1 h, the cooling bath is removed and the reaction temperature brought to room temperature. After overnight it is quenched by the addition of saturated ammonium chloride (2 mL). The resulting precipitate is dissolved with water and extracted three times with ethyl acetate (2 mL). The combined extracts are washed with brine and dried over sodium sulfate. Purification by chromatography (10 silica gel cartridge, 1:1 ethyl acetate/heptane) afforded 1-(2-pyrrolidin-1-ylmethyl-phenyl)-1-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-propan-1-ol (50 mg, Example 34) as white powder; 1H NMR [(CD3)2SO)]: δ 13.22 (1H, s), 11.48 (1H, s), 8.73 (1H, s), 7.74 (2H, m), 7.45 (1H, s), 7.41 (1H, t), 7.39-7.25 (4H, m), 6.93 (1H, d), 6.59 (1H, s), 2.68 (1H, d), 2.45 (2H), 2.25 (4H), 2.08 (1H), 1.74 (4H, m), 0.75 (3H, t); LC/MS: 457 (M+H).

Workup

  1. customthe cooling bath is removed
  2. custombrought to room temperature
  3. customAfter overnight it is quenched by the addition of saturated ammonium chloride (2 mL)
  4. dissolutionThe resulting precipitate is dissolved with water
  5. extractionextracted three times with ethyl acetate (2 mL)
  6. washThe combined extracts are washed with brine
  7. dry with materialdried over sodium sulfate
  8. customPurification by chromatography (10 silica gel cartridge, 1:1 ethyl acetate/heptane)

Sources & evidence

ORD record
ord-97653532502e4d4688b11c6d7b35a991
Source dataset
uspto-grants-2009_04
Patent number
US07518000B2

Reaction notes

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