Tetrahydrofuran → HCID 10196386, compound

HRID 855509Notes

Reaction equation

HRID 855509 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[N:15]=[CH:16][S:17][C:11]=2[N:10]=[C:9]1[CH:18]([NH:21][CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1.C([BH3-])#N.[Na+].O1CCCC1>CO.C(O)(=O)C>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[N:15]=[CH:16][S:17][C:11]=2[N:10]=[C:9]1[CH:18]([N:21]([CH2:32][C:31]1[CH:34]=[CH:35][C:28]([Br:27])=[CH:29][CH:30]=1)[CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 707414-Bromobenzaldehyde2×HCID 5003444Sodium cyanoborohydride2×HCID 58935445HCID 58935445, compound

Product 1

HCID 10196386HCID 10196386, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 6-benzyl-5-(1-{[2-(dimethylamino)ethyl]amino}-propyl)[1,3]thiazolo[5,4-d]pyrimidin-7(6H)-one (14, 1 equiv) and 4-bromobenzaldehyde (2 equiv) in methanol is treated with a solution of sodium cyanoborohydride in tetrahydrofuran (1M, 2 equiv). Acetic acid is added to obtain a pH of 6-7 and the reaction is warmed at 60° C. for 18 h. An additional 2 equivalents of 4-bromobenzaldehyde and sodium cyanoborohydride are added after 18, 42 and 66 hours while maintaining the pH at 6-7 with acetic acid. After warming 90 h at 60° C., the reaction is concentrated and the residue is partitioned between EtOAc and aqueous saturated NaHCO3 solution. The organic layer is washed with brine, dried (MgSO4) and concentrated. The residue is purified by flash chromatography. Elution with EtOAc to 5% NH3-EtOH/EtOAC gives 6-benzyl-5-(1-{(4-bromobenzyl)[2-(dimethylamino)ethyl]amino}propyl)[1,3]thiazolo[5,4-d]pyrirnidin-7(6H)-one (2-1).

Workup

  1. customto obtain a pH of 6-7
  2. temperatureAfter warming 90 h at 60° C.
  3. concentrationthe reaction is concentrated
  4. customthe residue is partitioned between EtOAc and aqueous saturated NaHCO3 solution
  5. washThe organic layer is washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue is purified by flash chromatography
  9. washElution with EtOAc to 5% NH3-EtOH/EtOAC

Sources & evidence

ORD record
ord-90cd668e43794a57bd6e7b58fd955641
Source dataset
uspto-grants-2007_08
Patent number
US07262187B2

Reaction notes

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