Hydrochloric Acid → (3R)-1-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-3-pyrrolidinol

HRID 79171Notes

Reaction equation

HRID 79171 reaction equation
[Si]([O:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:21]3[N:22]=[CH:23][C:24]4[C:29]5[CH:30]=[CH:31][N:32]=[C:33]([F:34])[C:28]=5[N:27]([CH:35]5[CH2:39][CH2:38][CH2:37][CH2:36]5)[C:25]=4[N:26]=3)=[N:18][CH:19]=2)[CH2:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl.C(OCC)C>C1COCC1.CO.C(O)C>[CH:35]1([N:27]2[C:25]3[N:26]=[C:21]([NH:20][C:17]4[N:18]=[CH:19][C:14]([N:11]5[CH2:12][CH2:13][C@@H:9]([OH:8])[CH2:10]5)=[CH:15][CH:16]=4)[N:22]=[CH:23][C:24]=3[C:29]3[CH:30]=[CH:31][N:32]=[C:33]([F:34])[C:28]2=3)[CH2:36][CH2:37][CH2:38][CH2:39]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 2724141Tetrabutylammonium FluorideHCID 58299699N-(5-((3R)-3-((tert-butyl(dimethyl)silyl)oxy)-1-pyrrolidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 58299703(3R)-1-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-3-pyrrolidinolYield 50.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Compound 278 (58 mg, 106 μmol) was dissolved in THF (2 mL). Tetrabutylammonium fluoride, 1.0M in THF (0.5 mL, 0.500 mmol) was added and the reaction stirred at room temperature for 4 hours. The solvent was removed to give an orange oil. Silica gel chromatography (gradient elution ethyl acetate+2.5% TEA/0-5% methanol) afforded a yellow solid. This residue was taken up in methanol (2 mL) and HCl in ethanol (1.0M, 0.5 mL) was added. Diethyl ether (20 mL) was added to precipitate the product, which was filtered and dried in vacuo to give compound 277 as a yellow solid (23 mg, 50%). 1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1 H) 9.25-9.35 (m, 1 H) 7.94-8.11 (m, 4 H) 7.62-7.77 (m, 2 H) 7.05 (dd, J=8.93, 2.81 Hz, 1 H) 5.37-5.54 (m, 1 H) 4.99 (d, J=3.91 Hz, 1 H) 4.44 (br. s., 1 H) 3.46 (dd, J=10.03, 4.89 Hz, 2 H) 3.05-3.16 (m, 1 H) 2.26-2.42 (m, 3 H) 1.96-2.20 (m, 8 H) 1.85-1.96 (m, 2 H) 1.66-1.83 (m, 3 H) ppm.

Workup

  1. customThe solvent was removed
  2. customto give an orange oil
  3. washSilica gel chromatography (gradient elution ethyl acetate+2.5% TEA/0-5% methanol)
  4. customafforded a yellow solid
  5. customto precipitate the product, which
  6. filtrationwas filtered
  7. customdried in vacuo

Sources & evidence

ORD record
ord-d51c0bd118764eb387771a87ff736ac8
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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