Lithium aluminum hydride → 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentane-1,5-diol

HRID 1501447

Reaction equation

HRID 1501447 reaction equation
[CH3:1][Si:2]([CH3:35])([CH3:34])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([C:16]3[CH:17]=[N:18][N:19]([CH:21]([CH2:28][C:29](OCC)=[O:30])[CH2:22][C:23](OCC)=[O:24])[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1.[AlH4-].[Li+]>C1COCC1>[CH3:35][Si:2]([CH3:1])([CH3:34])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([C:16]3[CH:17]=[N:18][N:19]([CH:21]([CH2:22][CH2:23][OH:24])[CH2:28][CH2:29][OH:30])[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1

Participants

4

Reactant 2

HCID 28112Lithium aluminum hydrideHCID 57477879Diethyl 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedioate

Product 1

HCID 574778783-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentane-1,5-diolYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Diethyl 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedioate, prepared substantially as described in Example 407 (0.80 g, 0.0016 mol), was dissolved in THF (40 mL, 0.49 mol) and cooled in an ice bath under a nitrogen atmosphere. To this mixture, 1.0 M lithium tetrahydroaluminate in THF (3.2 mL) was added slowly. The reaction was stirred for 1 h, quenched with ice and partitioned between ethyl acetate and 1 N HCl. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to give an amber oil. The product was purified by FCC on silica gel eluting with an ethyl acetate: methanol gradient to give 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentane-1,5-diol as a clear viscous oil (0.51 gm, 76%), LC/MS (M+H)+: 418, 1H NMR (DMSO-d6) 6, 8.85 (s, 1H), 8.41 (s, 1H), 8.37 (s, 1H), 7.45 (d, 1H), 6.83 (d, 1H), 5.73 (s, 2H), 4.91 (m, 1H), 3.75 (m, 2H), 3.59 (m, 2H), 3.45 (m, 2H), 2.18 (m, 4H), 0.95 (m, 2H), 0.1 (s, 9H).

Workup

  1. temperaturecooled in an ice bath under a nitrogen atmosphere
  2. customquenched with ice
  3. custompartitioned between ethyl acetate and 1 N HCl
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give an amber oil
  8. customThe product was purified by FCC on silica gel eluting with an ethyl acetate

Sources & evidence

ORD record
ord-4947f2debd3f4419b2692b14c83093fc
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Linked notes

Loading…