Sodium Hydroxide → (R)-4-amino-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

HRID 510358Notes

Reaction equation

HRID 510358 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[C:9](C#N)[N:8]([C@@H:26]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[OH-:38].[Na+].[CH2:40]([OH:43])CO.O>>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:15][CH:16]=3)=[C:9]([C:40]([OH:43])=[O:38])[N:8]([C@@H:26]3[CH2:30][CH2:29][NH:28][CH2:27]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 20437942Ethylene glycol waterHCID 86719398(R)-tert-butyl 3-(4-amino-6-cyano-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86719406(R)-4-amino-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acidYield 4%

Conditions

Temperature
150 °C

Procedure

To a mixture of (R)-tert-butyl 3-(4-amino-6-cyano-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (101) (2.0 g, 4.0 mmol) in ethylene glycol/H2O (20 mL/5 mL) was added and NaOH (1.0 g, 25 mmol). The reaction mixture was purged with N2 (2×) before heated at 150° C. overnight. After cooling to r.t., the reaction was diluted with ice-water, neutralized to pH 7 by slow addition of con. HCl. The aqueous layer was washed with DCM, concentrated under vacuum. Part of the residue was purified by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% HCOOH)) to give (R)-4-amino-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (127) (60 mg, 4%) as a white solid. LC-MS (ESI): m/z (M+1) 416.0.

Workup

  1. additionwas added
  2. customThe reaction mixture was purged with N2 (2×)
  3. temperatureAfter cooling to r.t.
  4. additionthe reaction was diluted with ice-water
  5. additionneutralized to pH 7 by slow addition of con
  6. washThe aqueous layer was washed with DCM
  7. concentrationconcentrated under vacuum
  8. customPart of the residue was purified by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% HCOOH))

Sources & evidence

ORD record
ord-0b312ae7ce034da29e14e1ebf0f12186
Source dataset
uspto-grants-2015_08
Patent number
US09096604B2

Reaction notes

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