Tetrahydrofuran → HCID 118061901, compound

HRID 920809Notes

Reaction equation

HRID 920809 reaction equation
[F:1][C:2]1([F:10])[CH2:6][CH2:5][CH:4](C(O)=O)[CH2:3]1.C1C=CC(P([N:25]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:28][C:29]1[CH:30]=[C:31]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][NH:41][CH2:42][CH2:43][N:38]3[N:37]=2)[CH:32]=[CH:33][C:34]=1[F:35].C1[CH2:52][O:51]CC1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:28][C:29]1[CH:30]=[C:31]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][N:41]([C:52]([NH:25][CH:4]4[CH2:5][CH2:6][C:2]([F:1])([F:10])[CH2:3]4)=[O:51])[CH2:42][CH2:43][N:38]3[N:37]=2)[CH:32]=[CH:33][C:34]=1[F:35]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 534038373,3-Difluorocyclopentane-1-carboxylic acidHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

Product 1

HCID 118061901HCID 118061901, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A stirred solution of Intermediate 332C (32.6 mg, 0.217 mmol) in toluene (1 mL) at RT under nitrogen was added with TEA (0.045 mL, 0.325 mmol) and DPPA (0.050 mL, 0.217 mmol) and heated to 70° C. for 2 h. The reaction mass was cooled to RT and to it was added a solution of Intermediate 185B (30 mg, 0.108 mmol) in THF (1 mL) and stirred at RT for 16 h. The reaction mass was diluted with ethyl acetate (25 mL), washed with water and brine, dried over anhydrous Na2SO4, filtered, and the filtrate concentrated under reduced pressure. The individual isomers were separated by preparative chiral SFC (Column: WHELK-O® 1 (R,R) (250×4.6 mm), 5μ column, 5 Co-Solvent: 0.2% DEA, Column Temperature: 24.4, Total Flow: 3 mL, CO2 Flow Rate: 2.1, Co-Solvent Flow Rate: 0.9, Co-Solvent %: 30%, Back Pressure: 101 bar.

Workup

  1. temperatureThe reaction mass was cooled to RT and to it
  2. washwashed with water and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe individual isomers were separated by preparative chiral SFC (Column

Sources & evidence

ORD record
ord-14f80af829e246b6a911eefc35597fd8
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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