Triethylamine → (R)-N-(1-(2-(tert-butyldiphenylsilyloxy)ethyl)-1H-pyrazol-5-yl)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1426977Notes

Reaction equation

HRID 1426977 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24]([OH:26])=O)=[C:17]3[N:16]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.C(N(CC)CC)C.[Si:46]([O:63][CH2:64][CH2:65][N:66]1[C:70]([NH2:71])=[CH:69][CH:68]=[N:67]1)([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CN(C=O)C>[Si:46]([O:63][CH2:64][CH2:65][N:66]1[C:70]([NH:71][C:24]([C:23]2[CH:22]=[N:21][N:18]3[CH:19]=[CH:20][C:15]([N:11]4[CH2:12][CH2:13][CH2:14][C@@H:10]4[C:4]4[C:5]([O:8][CH3:9])=[N:6][CH:7]=[C:2]([F:1])[CH:3]=4)=[N:16][C:17]=23)=[O:26])=[CH:69][CH:68]=[N:67]1)([C:59]([CH3:60])([CH3:61])[CH3:62])([C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 66847769HCID 66847769, compoundHCID 674711071-(2-(tert-butyldiphenylsilyloxy)ethyl)-1H-pyrazol-5-amine

Product 1

HCID 67471089(R)-N-(1-(2-(tert-butyldiphenylsilyloxy)ethyl)-1H-pyrazol-5-yl)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 46.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of (R)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (220 mg, 0.616 mmol) in DMF (5 mL) was added dropwise 2,4,6-trichlorobenzoyl chloride (106 μL, 0.677 mmol) and triethylamine (81.0 mg, 0.800 mmol). The reaction was stirred for 2 hours, and 1-(2-(tert-butyldiphenylsilyloxy)ethyl)-1H-pyrazol-5-amine (338 mg, 0.923 mmol) was added to the reaction mixture. The reaction was heated to 60° C. for 3 hours and then cooled to ambient temperature. The solvent was removed under reduced pressure and the residue was purified by silica column chromatography to afford the desired product (201 mg, 46.3% yield). MS (apci) m/z=705.1 (M+H).

Workup

  1. temperaturecooled to ambient temperature
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was purified by silica column chromatography

Sources & evidence

ORD record
ord-5dd5a1f7b0014e48ab1efd0c41dcf84c
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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