Sodium Hydroxide → {3-oxo-1-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile

HRID 1426333Notes

Reaction equation

HRID 1426333 reaction equation
[OH:1][CH:2]1[CH2:5][C:4]([CH2:28][C:29]#[N:30])([N:6]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]4[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[CH:19][C:12]=34)[CH:8]=[N:7]2)[CH2:3]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[OH-].[Na+]>C(Cl)Cl>[O:1]=[C:2]1[CH2:3][C:4]([CH2:28][C:29]#[N:30])([N:6]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]4[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:27])[CH3:26])[CH:18]=[CH:19][C:12]=34)[CH:8]=[N:7]2)[CH2:5]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 159087TriacetoxyperiodinaneHCID 67968346{3-hydroxy-1-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile

Product 1

HCID 69675438{3-oxo-1-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {3-hydroxy-1-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile (1.3 g, 3.1 mmol, a mixture of diastereomers from Step B) in methylene chloride (40 mL) was added Dess-Martin periodinane (1.63 g, 3.84 mmol). After stirring for 1 hour and 15 minutes, the reaction mixture was poured into 1N NaOH and extracted with three portions of DCM. The combined extracts were washed with 1N NaOH, then brine, dried over sodium sulfate, decanted and solvent was removed in vacuo. Flash chromatography on silica gel, eluting with an initial gradient from 0-30% EtOAc/Hexanes, then a rapid gradient up to 100% EtOAc afforded product (1.1 g, 85%). 1H NMR (300 MHz, CDCl3) δ 8.34 (d, J=5.0 Hz, 1H), 8.14 (s, 1H), 8.11 (s, 1H), 7.42 (d, J=3.7 Hz, 1H), 7.18 (d, J=5.0 Hz, 1H), 6.71 (d, J=3.7 Hz, 1H), 5.71 (s, 2H), 4.10-3.97 (m, 2H), 3.74-3.61 (m, 2H), 3.61-3.47 (m, 2H), 3.28 (s, 2H), 0.98-0.86 (m, 2H), −0.07 (s, 9H); LCMS (M+H)+: 422.2.

Workup

  1. extractionextracted with three portions of DCM
  2. washThe combined extracts were washed with 1N NaOH
  3. dry with materialbrine, dried over sodium sulfate
  4. customdecanted
  5. customsolvent was removed in vacuo
  6. washFlash chromatography on silica gel, eluting with an initial gradient from 0-30% EtOAc/Hexanes

Sources & evidence

ORD record
ord-9fd8d98a55044587aefcfad26d65125e
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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