Diisopropylethylamine → HCID 136009379, compound

HRID 1969641Notes

Reaction equation

HRID 1969641 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17](S(C5C=CC(C)=CC=5)(=O)=O)[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:30][S:31]([CH:34]=[CH2:35])(=[O:33])=[O:32])[CH2:4]1)[CH3:2].CCN(C(C)C)C(C)C.[NH:45]1[CH:49]=[C:48]([C:50]#[N:51])[CH:47]=[N:46]1>C(O)CC.C(Cl)Cl>[C:50]([C:48]1[CH:49]=[N:45][N:46]([CH2:35][CH2:34][S:31]([NH:30][C@@H:5]2[CH2:6][C@H:7]([C:8]3[N:12]4[C:13]5[CH:19]=[CH:18][NH:17][C:14]=5[N:15]=[CH:16][C:11]4=[N:10][N:9]=3)[C@H:3]([CH2:1][CH3:2])[CH2:4]2)(=[O:32])=[O:33])[CH:47]=1)#[N:51]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5644491H-Pyrazole-4-carbonitrileHCID 58557463HCID 58557463, compound

Product 1

HCID 136009379HCID 136009379, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)ethenesulfonamide (0.065 g, 0.13 mmol, prepared using K.1 from Example #8 Step M and 2-chloroethanesulfonyl chloride with TEA), DIEA (0.30 mL, 1.7 mmol) and 1H-pyrazole-4-carbonitrile (0.047 g, 0.51 mmol, American Custom Chemicals Corp) in n-PrOH (2.0 mL) was stirred for about 2 h at about 60° C. then at about 80° C. for about 18 h. The reaction mixture was cooled to ambient temperature and concd under reduced pressure. The crude residue was dissolved in DCM (10 mL), washed with saturated NaHCO3 (5 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to give 2-(4-cyano-1H-pyrazol-1-yl)-N-((1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)ethanesulfonamide (0.024 g, 42%): LC/MS (Table 1, Method b) Rt=1.63 min; MS m/z: 454 (M+H)+.

Workup

  1. waitat about 80° C. for about 18 h
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. washwashed with saturated NaHCO3 (5 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customThe crude material was purified by silica gel chromatography
  7. washeluting with a gradient of 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-c36a19a7de63401bbad95f7678831f50
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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