Sodium Hydroxide → 5-[3-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)-propyl]-thiophene-2-carboxylic acid

HRID 889075Notes

Reaction equation

HRID 889075 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([CH2:10][CH2:11][CH2:12][C:13]2[NH:23][C:16]3[N:17]=[C:18]([NH2:22])[NH:19][C:20](=[O:21])[C:15]=3[CH:14]=2)=[CH:8][CH:9]=1)=[O:4].[OH-].[Na+].CO.C(Cl)(Cl)Cl>CO>[NH2:22][C:18]1[NH:19][C:20](=[O:21])[C:15]2[CH:14]=[C:13]([CH2:12][CH2:11][CH2:10][C:7]3[S:6][C:5]([C:3]([OH:4])=[O:2])=[CH:9][CH:8]=3)[NH:23][C:16]=2[N:17]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21584188Chloroform methanolHCID 1363814275-[3-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)-propyl]-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 1360441775-[3-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)-propyl]-thiophene-2-carboxylic acidYield 88.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 8 (300 mg, 0.9 mmol) in MeOH (10 mL) was added 1 N NaOH (10 mL) and the mixture was stirred under N2 at room temperature for 16 h. TLC showed the disappearance of the starting material (Rf=0.56) and one major spot at the origin (MeOH/CHCl3 1:5). The reaction mixture was evaporated to dryness under reduced pressure. The residue was dissolved in water (10 mL), the resulting solution was cooled in an ice bath, and the pH was adjusted to 3-4 with dropwise addition of 1 N HCl. The resulting suspension was frozen in a dry ice-acetone bath, thawed to 4-5° C. in the refrigerator, and filtered. The residue was washed with a small amount of cold water and dried in vacuum using P2O5 to afford 254 mg of 9 as white powder. 1H NMR (DMSO-d6): δ 1.89-1.96 (m, 2H), 2.49-2.55 (t, J=7.2 Hz, 2H), 2.80-2.84 (t, J=7.2 Hz, 2H), 5.88 (s, 1H), 5.98 (s, 2H), 6.92-6.93 (d, J=3.6 Hz, 1H), 7.55-7.56 (d, J=3.6 Hz, 1H), 10.14 (s, 1H), 10.83 (s, 1H) 12.86 (br, 1H).

Workup

  1. customThe reaction mixture was evaporated to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in water (10 mL)
  3. temperaturethe resulting solution was cooled in an ice bath
  4. additionthe pH was adjusted to 3-4 with dropwise addition of 1 N HCl
  5. temperatureThe resulting suspension was frozen in a dry ice-acetone bath
  6. customthawed to 4-5° C. in the refrigerator
  7. filtrationfiltered
  8. washThe residue was washed with a small amount of cold water
  9. customdried in vacuum

Sources & evidence

ORD record
ord-89a984af91d5446a902b2bc3e3a7c4bc
Source dataset
uspto-grants-2012_08
Patent number
US08252804B2

Reaction notes

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