Water → 2-(4-(6-((9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-1-piperazinyl)ethanol

HRID 875983Notes

Reaction equation

HRID 875983 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][O:30][Si](C(C)(C)C)(C)C)[CH2:24][CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:38]=[CH:39][N:40]=[C:41]([F:42])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O.[OH-].[Na+]>C1COCC1>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:17]=[CH:18][C:19]([N:22]5[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][OH:30])[CH2:24][CH2:23]5)=[CH:20][CH:21]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:38]=[CH:39][N:40]=[C:41]([F:42])[C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 2724141Tetrabutylammonium FluorideHCID 582997739-Cyclopentyl-N-(5-(4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 583001122-(4-(6-((9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-1-piperazinyl)ethanolYield 77.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To compound 248 (0.115 g, 0.19 mmol) in THF (1.0 mL) was added tetrabutylammonium fluoride, 1.0 M in THF (0.49 mL, 0.49 mmol). The reaction was stirred at room temperature. After 1 h, the reaction contents were poured into water. The aqueous layer was brought to pH 12 with 5 N NaOH and extracted with 10% methanol in dichloromethane (3×25 mL). The combined organics were dried with Na2SO4 and concentrated in vacuo. Silica gel chromatography (gradient elution 3 to 7.5% 2M methanolic NH3 in DCM) afforded compound 242 (0.070 g, 75% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.68-1.80 (m, 2 H) 1.92-2.05 (m, 2 H) 2.05-2.17 (m, 2 H) 2.25-2.40 (m, 2 H) 2.45 (t, J=6.11 Hz, 2 H) 2.54-2.62 (m, 4 H) 3.00-3.27 (m, 4 H) 3.54 (q, J=5.95 Hz, 2 H) 4.43 (t, J=5.26 Hz, 1 H) 5.45 (quin, J=9.05 Hz, 1 H) 7.47 (dd, J=9.17, 2.81 Hz, 1 H) 7.93-8.07 (m, 3 H) 8.11 (d, J=9.05 Hz, 1 H) 9.32 (s, 1 H) 9.89 (s, 1 H) ppm.

Workup

  1. customthe reaction contents
  2. extractionextracted with 10% methanol in dichloromethane (3×25 mL)
  3. dry with materialThe combined organics were dried with Na2SO4
  4. concentrationconcentrated in vacuo
  5. washSilica gel chromatography (gradient elution 3 to 7.5% 2M methanolic NH3 in DCM)

Sources & evidence

ORD record
ord-41996886d84d41489363a737f4972982
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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