HCID 135499784, compound → HCID 136016230, compound

HRID 2078695Notes

Reaction equation

HRID 2078695 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-e578183db7514cd1a4d45353f5fb22c2
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

Loading…