Carbon Tetrachloride → (S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

HRID 539007Notes

Reaction equation

HRID 539007 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5]([NH:7][NH:8][C:9](=O)[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[N:18][N:19]3[CH:24]=[CH:23][C:22]([N:25]4[C@@H:29]([CH:30]([CH3:32])[CH3:31])[CH2:28][O:27][C:26]4=[O:33])=[N:21][C:20]=23)=[CH:12][CH:11]=1)=[O:6].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C.C(Cl)(Cl)(Cl)Cl>ClCCl.CC#N.CCOC(C)=O>[OH:1][CH2:2][CH2:3][NH:4][C:5]1[O:6][C:9]([C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][C:22]([N:25]5[C@@H:29]([CH:30]([CH3:32])[CH3:31])[CH2:28][O:27][C:26]5=[O:33])=[N:21][C:20]=34)=[CH:14][CH:15]=2)=[N:8][N:7]=1

Participants

8

Reactant 4

HCID 5943Carbon TetrachlorideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67033962(S)-N-(2-hydroxyethyl)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarboxamide

Product 1

HCID 68088822(S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneYield 35.9%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of (S)—N-(2-hydroxyethyl)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarboxamide (14.4 mg, 0.031 mmol) in dichloromethane (1 mL) and MeCN (1 mL) was added PS-triphenylphosphine resin (0.054 g, 2.28 mmol/g, 0.123 mmol), triethylamine (44 μL, 0.308 mmol), and CCl4 (12 μL, 0.123 mmol), and the reaction mixture was heated to 50° C. for 4 hours. After the mixture was cooled at ambient temperature, the reaction mixture was treated with EtOAc, washed with water, dried over MgSO4, and concentrated under reduced pressure. The crude was then purified by preparative plate silica gel chromatography (10% MeOH in dichloromethane) to afford 5 mg (35%) of (S)-3-(3-(4-(5-(2-hydroxyethylamino)-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one. 1H NMR (400 MHz, CDCl3) δ 8.60 (d, 1H), 8.43 (s, 1H), 8.08 (m, 3H), 7.92 (d, 2H), 4.96 (m, 1H), 4.44 (m, 2H), 3.94 (t, 2H), 3.65 (m, 2H), 2.88 (m, 1H), 1.09 (d, 3H), 0.95 (d, 3H); LCMS (APCI+) m/z 450.6 [M+H]+.

Workup

  1. temperatureAfter the mixture was cooled at ambient temperature
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was then purified by preparative plate silica gel chromatography (10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-e50f7a0467164d5bb4fb69c7ad7c2e79
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

Loading…