HCID 86691754, compound → HCID 178522348, compound

HRID 1426978Notes

Reaction equation

HRID 1426978 reaction equation
[Si]([O:18][CH2:19][CH2:20][N:21]1[C:25]([NH:26][C:27]([C:29]2[C:37]3[N:36]=[C:35]([N:38]4[CH2:42][CH2:41][CH2:40][C@@H:39]4[C:43]4[C:44]([O:50]C)=[N:45][CH:46]=[C:47]([F:49])[CH:48]=4)N=CC=3NN=2)=[O:28])=[CH:24][CH:23]=[N:22]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>Cl.O1CCOCC1>[F:49][C:47]1[CH:48]=[C:43]([C@H:39]2[CH2:40][CH2:41][CH2:42][N:38]2[C:35]2[CH:19]=[CH:20][N:21]3[N:22]=[CH:23][C:29]([C:27]([NH:26][C:25]4[N:21]([CH2:20][CH2:19][OH:18])[N:22]=[CH:23][CH:24]=4)=[O:28])=[C:37]3[N:36]=2)[C:44]([OH:50])=[N:45][CH:46]=1

Participants

4

Reactant 1

HCID 86691754HCID 86691754, compound

Product 1

HCID 178522348HCID 178522348, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of (R)-N-(1-(2-(tert-butyldiphenylsilyloxy)ethyl)-1H-pyrazol-5-yl)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo pyrimidine-3-carboxamide (201 mg, 0.285 mmol) in 4M HCl in dioxane (6 mL) was sealed and heated to 100° C. for fours hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was diluted with DCM (20 mL) and washed with saturated NaHCO3 (5 mL), water (5 mL) and brine (5 mL). The organic layer was concentrated to give crude (R)-5-(2-(5-fluoro-2-hydroxypyridin-3-yl)pyrrolidin-1-yl)-N-(1-(2-hydroxyethyl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide, to which was added THF (20 mL), DEAD (53.9 μL, 0.342 mmol) and triphenylphosphine (89.8 mg, 0.342 mmol). The reaction mixture was stirred for 18 hours, then concentrated under vacuum. The residue was purified by silica column chromatography, eluting with 10% MeOH/DCM to afford the title compound (1.8 mg, 1.5% yield). MS (apci) m/z=435.3 (M+H).

Workup

  1. customwas sealed
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with DCM (20 mL)
  5. washwashed with saturated NaHCO3 (5 mL), water (5 mL) and brine (5 mL)
  6. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-30bd24a869c749609b700d66ef971abd
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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