Sodium Hydroxide → HCID 25181609, compound

HRID 500743Notes

Reaction equation

HRID 500743 reaction equation
C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([C:19]4[C:23]([C:24]5[CH:29]=[CH:28][N:27]=[C:26]([NH:30][CH2:31][C@@H:32]([OH:34])[CH3:33])[N:25]=5)=[CH:22][N:21]([CH2:35][C:36]#[N:37])[N:20]=4)[CH:18]=[C:13]3[CH:12]=[CH:11]2)(=O)=O)C=CC=CC=1.[OH-].[Na+]>C1COCC1.CO>[OH:34][C@@H:32]([CH3:33])[CH2:31][NH:30][C:26]1[N:25]=[C:24]([C:23]2[C:19]([C:17]3[CH:18]=[C:13]4[CH:12]=[CH:11][NH:10][C:14]4=[N:15][CH:16]=3)=[N:20][N:21]([CH2:35][C:36]#[N:37])[CH:22]=2)[CH:29]=[CH:28][N:27]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 57856352HCID 57856352, compound

Product 1

HCID 25181609HCID 25181609, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To solution of the {3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-[2-((S)-2-hydroxy-propylamino)-pyrimidin-4-yl]-pyrazol-1-yl}-acetonitrile (C-1-6) (145 mg, 0.28 mmol) in THF (5 mL) at −40° C. was added sodium hydroxide (1.1 mL of a 10 mg/mL solution in MeOH, 0.28 mmol). The mixture was allowed to slowly warm to 0° C. After 2 hr the mixture was diluted with 10 mL THF and stirring continued at 0° C. for 2 hr. Mixture was partitioned between pH 7 phosphate buffer and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organics were washed with saturated aqueous NaCl, dried over MgSO4 and reduced to minimum volume. The residue was purified by HPLC to give the [4-[2-((S)-2-Hydroxy-propylamino)-pyrimidin-4-yl]-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-pyrazol-1-yl]-acetonitrile (C-1) in 23% yield. 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 9.78 (br. s., 1H), 8.42 (d, J=2.02 Hz, 1H), 8.22 (s, 1H), 8.05-8.14 (m, 2H), 7.38-7.45 (m, 1H), 6.42-6.56 (m, 2H), 5.74 (br. s., 1H), 5.25 (s, 2H), 3.72 (br. s., 1H), 3.19 (br. s., 1H), 3.04 (br. s., 1H), 0.95 (br. s., 3H).

Workup

  1. customMixture was partitioned between pH 7 phosphate buffer and ethyl acetate
  2. extractionThe aqueous layer was extracted twice with ethyl acetate
  3. washThe combined organics were washed with saturated aqueous NaCl
  4. dry with materialdried over MgSO4
  5. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-6f3a6b16c7c4489a9060558d507866c7
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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