Ethanol → HCID 58557468, compound

HRID 1969762Notes

Reaction equation

HRID 1969762 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:20]([C:23]5[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH2:30])[CH2:4]1)[CH3:2].CCO.CCN(C(C)C)C(C)C.Cl[C:44]1[S:45][C:46]([C:49]#[N:50])=[CH:47][N:48]=1>C(Cl)Cl>[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:20]([C:23]5[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:30][C:44]2[S:45][C:46]([C:49]#[N:50])=[CH:47][N:48]=2)[CH2:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 14852222-Chlorothiazole-5-carbonitrileHCID 58557840(1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

Product 1

HCID 58557468HCID 58557468, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (0.20 g, 0.47 mmol), EtOH (1.3 mL), DIEA (0.33 mL, 1.88 mmol), and 2-chlorothiazole-5-carbonitrile (0.082 g, 0.56 mmol, Ark Pharm) was heated in a CEM microwave at about 150° C. for about 30 min (250 psi maximum pressure, 5 min maximum ramp, 300 maximum watts). The reaction mixture was cooled to ambient temperature and concd under reduced pressure. The crude oil was dissolved in DCM (10 mL) and washed with water (2×10 mL). The organic layer was dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude mixture was purified by silica gel chromatography eluting with a gradient of 0-70% EtOAc in DCM to give 2-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)thiazole-5-carbonitrile (0.21 g, 84%): LC/MS (Table 1, Method c) Rt=1.53 min; MS m/z: 533 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washwashed with water (2×10 mL)
  3. dry with materialThe organic layer was dried over anhydrous MgSO4
  4. filtrationfiltered
  5. customThe crude mixture was purified by silica gel chromatography
  6. washeluting with a gradient of 0-70% EtOAc in DCM

Sources & evidence

ORD record
ord-45c875916e384ed8bc04f8fa746ebb93
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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