Thioglycolic Acid → [(6-Amino-9-benzyl-9H-purin-8-yl)thio]acetic acid

HRID 1422558Notes

Reaction equation

HRID 1422558 reaction equation
[C:1]([OH:5])(=[O:4])[CH2:2][SH:3].[H-].[Na+].Br[C:9]1[N:10]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:11]2[C:16]([N:17]=1)=[C:15]([NH2:18])[N:14]=[CH:13][N:12]=2>CN(C=O)C>[C:1]([CH2:2][S:3][C:9]1[N:10]([CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:11]2[C:16]([N:17]=1)=[C:15]([NH2:18])[N:14]=[CH:13][N:12]=2)([OH:5])=[O:4]

Participants

5

Reactant 3

HCID 1133Thioglycolic AcidHCID 24758Sodium hydrideHCID 99045519-Benzyl-8-bromoadenine

Product 1

HCID 2772491[(6-Amino-9-benzyl-9H-purin-8-yl)thio]acetic acidYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of thioglycolic acid (0.05 mL, 0.68 mmol) and NaH (0.05 g, 1.35 mmol, 60% in oil) in anhydrous DMF (3 mL) was stirred for 30 min at 0° C. under argon, then 23 (0.13 g, 0.45 mmol) in DMF (3 mL) was added. After stirring overnight at room temperature, the reaction mixture was concentrated to dryness, and the crude product was purified by reverse phase HPLC (5-50% ACN in TEAA over 20 min) to give 24 (0.07 g, 50%). Rt (0-10% A in B over 20 min.) 10.36 min.; 1H NMR (DMSO-d6) δ: 4.17 (s, 2H, SCH2), 5.31 (s, 2H, CH2), 7.10 (bs, 2H, NH2), 7.29 (m, 3H, H arom.), 7.35 (m, 2H, H arom.), 8.12 (s, 1H, H2); 13C NMR (DMSO-d6) δ: 34.91 (SCH2), 45.97 (CH2), 119.17 (C5), 127.77, 128.22 and 129.15 (CH), 136.63 (Cq), 147.77 (C8), 152.02 (C4), 152.51 (C2), 154.62 (C6); 169.85 (CO); HRMS (ESI-TOF) m/z calcd for [C14H13N5O2S+H]316.0868; found 316.0855.

Workup

  1. concentrationthe reaction mixture was concentrated to dryness
  2. customthe crude product was purified by reverse phase HPLC (5-50% ACN in TEAA over 20 min)

Sources & evidence

ORD record
ord-a199c3e77ebd4234be1bdac2b36105fb
Source dataset
uspto-grants-2015_01
Patent number
US08927520B2

Reaction notes

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