Water → HCID 178421992, compound

HRID 2053016Notes

Reaction equation

HRID 2053016 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:8][C@H:7]([N:9]2[C:13]3[N:14]=[CH:15][N:16]=[C:17]([NH2:18])[C:12]=3[C:11]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:20]=3)=[C:10]2[CH3:33])[CH2:6]1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[NH2:18][C:17]1[C:12]2[C:11]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:20]=3)=[C:10]([CH3:33])[N:9]([C@H:7]3[CH2:8][C@H:5]([CH2:3][OH:2])[CH2:6]3)[C:13]=2[N:14]=[CH:15][N:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 178501317HCID 178501317, compound

Product 1

HCID 178421992HCID 178421992, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2.94 g (6.64 mmol) trans-3-[4-amino-5-(3-benzyloxy-phenyl)-6-methyl-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutanecarboxylic acid methyl ester of Example 104 in 35 ml dry THF are added during 45 min to an ice-cold solution of 0.281 g (7.17 mmol) lithium aluminiumhydride in 30 ml dry THF. The reaction mixture is stirred at 0° C. for additional 20 h. Water is added slowly to the mixture (0.914 ml in 20 min; T≦4° C.), followed by 0.11 ml 4N NaOH. The precipitate is filtered off, the residue on the filter washed with ethyl acetate and water. The filtrate is extracted with ethyl acetate. After drying the organic phase with sodium sulfate, the solvent is evaporated and the residue purified by chromatography (solvent: ethyl acetate-MeOH 95:5). The title compound is obtained as a foam. Analytical HPLC: tR=3.06 min (shorty); ES-MS: m/eo=415; NMR (DMSO-d6): 8.10/s (1H), 7.25-7.5/several m's (6H), 7.25/“d” (1H); 6.95/s (1H); 6.90/1“d” (1H); 5.5-6.0/b (NH2); 5.13/s (2H); 5.04/m (1H); 4.69/t (OH); 3.57/t (2H); 3.15-3.25/m (2H); 2.4-2.5/m (1H); 2.23/s (3H); 2.15-2.25/m (2H).

Workup

  1. filtrationThe precipitate is filtered off
  2. washthe residue on the filter washed with ethyl acetate and water
  3. extractionThe filtrate is extracted with ethyl acetate
  4. dry with materialAfter drying the organic phase with sodium sulfate
  5. customthe solvent is evaporated
  6. customthe residue purified by chromatography (solvent: ethyl acetate-MeOH 95:5)

Sources & evidence

ORD record
ord-4c4aada7caef46228dbead6c7fa277a5
Source dataset
uspto-grants-2008_02
Patent number
US07326699B2

Reaction notes

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