Triethylamine → HCID 71516176, compound

HRID 574652Notes

Reaction equation

HRID 574652 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][C@@H:5]([OH:29])[C@@H:6]2[N:12]1[C:20]2[CH2:19][CH2:18][NH:17][CH2:16][C:15]=2[C:14]([C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=2)[C:24]#[N:25])=[N:13]1.[CH3:30][S:31](Cl)(=[O:33])=[O:32].C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][C@@H:5]([OH:29])[C@@H:6]2[N:12]1[C:20]2[CH2:19][CH2:18][N:17]([S:31]([CH3:30])(=[O:33])=[O:32])[CH2:16][C:15]=2[C:14]([C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=2)[C:24]#[N:25])=[N:13]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 89444385HCID 89444385, compound

Product 1

HCID 71516176HCID 71516176, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

To a solution of 3-[1-((1R,2R)-4,6-Dichloro-2-hydroxy-indan-1-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (13e) (0.02 g, 0.047 mmol) in dry tetrahydrofuran at −70° C. was added slowly and portionwise 100 μl of a solution of methanesulfonyl chloride (100 μl in 10 ml dry tetrahydrofuran) and after 5 min triethylamine (21 mg, 0.208 mmol). The mixture was stirred at −70° C. for 15 min and then a second portion of the methanesulfonyl/tetrahydrofuran solution above was added (100 μl). The mixture was stirred at −70° C. for 15 min and then a third portion of the methanesulfonyl/tetrahydrofuran solution above was added (50 μl). The mixture was stirred at −70° C. for 3 min, quenched with aqueous NaHCO3 and extracted 3 times with CH2Cl2. The combined organic layers were evaporated to dryness and the residue was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid) to give 15 mg of 3-[1-((1R,2R)-4,6-Dichloro-2-hydroxy-indan-1-yl)-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (23a).

Workup

  1. stirringThe mixture was stirred at −70° C. for 15 min
  2. stirringThe mixture was stirred at −70° C. for 3 min
  3. customquenched with aqueous NaHCO3
  4. extractionextracted 3 times with CH2Cl2
  5. customThe combined organic layers were evaporated to dryness
  6. customthe residue was purified by reverse phase HPLC (CH3CN/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-dfb8b68345014df197e016be34bba075
Source dataset
uspto-grants-2015_05
Patent number
US09034897B2

Reaction notes

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