Lithium Hydroxide → HCID 54670357, compound

HRID 1426975Notes

Reaction equation

HRID 1426975 reaction equation
C(OC([NH:8][C:9]([CH3:38])([CH3:37])[CH2:10][CH2:11][C:12]1[C:17]([C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:23]2[CH:28]=[CH:27][N:26]3[N:29]=[CH:30][C:31]([C:32]([O:34]C)=O)=[C:25]3[N:24]=2)=[CH:16][C:15]([F:36])=[CH:14][N:13]=1)=O)(C)(C)C.[OH-].[Li+].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.C(N(CC)CC)C>C1COCC1.CO.CN(C=O)C>[F:36][C:15]1[CH:16]=[C:17]2[C:12](=[N:13][CH:14]=1)[CH2:11][CH2:10][C:9]([CH3:37])([CH3:38])[NH:8][C:32](=[O:34])[C:31]1=[C:25]3[N:24]=[C:23]([CH:28]=[CH:27][N:26]3[N:29]=[CH:30]1)[N:19]1[C@@H:18]2[CH2:22][CH2:21][CH2:20]1

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67471116HCID 67471116, compound

Product 1

HCID 54670357HCID 54670357, compoundYield 48.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To (R)-methyl 5-(2-(2-(3-(tert-butoxycarbonylamino)-3-methylbutyl)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (166 mg, 0.315 mmol) in THF/MeOH (3 mL/1 mL) was added lithium hydroxide (946 μL, 1.89 mmol). The reaction vessel was sealed and heated to 70° C. for 3 hours. The reaction mixture was then dried under reduced pressure and HCl (4 mL, 4M in dioxane) was added. The reaction mixture was stirred for one hour, then the solvent was removed and the residue was dried under high vacuum for two hours. To the residue was then added DMF (8 mL), HOBT-H2O (96.5 mg, 0.630 mmol), EDCI (121 mg, 0.630 mmol) and triethylamine (159 mg, 1.58 mmol). The reaction mixture was stirred at 45° C. for 18 hours, then concentrated under vacuum The residue was purified by silica column chromatography eluting with 5% MeOH/DCM to afford the title compound (60.0 mg, 48.3% yield). MS (apci) m/z=395.1 (M+H).

Workup

  1. customThe reaction vessel was sealed
  2. dry with materialThe reaction mixture was then dried under reduced pressure and HCl (4 mL, 4M in dioxane)
  3. additionwas added
  4. customthe solvent was removed
  5. customthe residue was dried under high vacuum for two hours
  6. stirringThe reaction mixture was stirred at 45° C. for 18 hours
  7. concentrationconcentrated under vacuum The residue
  8. customwas purified by silica column chromatography
  9. washeluting with 5% MeOH/DCM

Sources & evidence

ORD record
ord-ad0f483e59c3478e8c88e8fcdd3ba497
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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