Acetyl chloride → 2-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-propane-1,3-diol

HRID 533201Notes

Reaction equation

HRID 533201 reaction equation
C(Cl)(=O)C.[NH2:5][CH:6]([CH2:9][OH:10])[CH2:7][OH:8].[CH2:11]([O:18][CH2:19][N:20]1[C:28]2[C:27]([O:29][CH3:30])=[N:26][CH:25]=[N:24][C:23]=2[C:22]([CH:31]=O)=[CH:21]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([BH3-])#N.[Na+]>CO>[CH2:11]([O:18][CH2:19][N:20]1[C:28]2[C:27]([O:29][CH3:30])=[N:26][CH:25]=[N:24][C:23]=2[C:22]([CH2:31][NH:5][CH:6]([CH2:9][OH:10])[CH2:7][OH:8])=[CH:21]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 68294SerinolHCID 5003444Sodium cyanoborohydrideHCID 577250835-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde

Product 1

HCID 252231892-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-propane-1,3-diolYield 77%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetyl chloride (0.117 ml, 1.65 mmol) was added to a stirred solution of 2-aminopropane-1,3-diol (0.3 g, 3.29 mmol) and 5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde (0.196 g, 0.659 mmol, prepared as in G. B. Evans, R. H. Furneaux, A, Lewandowicz, V. L. Schramm and P. C. Tyler, J. Med. Chem., 2003, 46, 3412) in MeOH (5 ml). Sodium cyanoborohydride (0.062 g, 0.988 mmol) was added and the mixture was stirred at rt overnight. The solvent was evaporated and the residue chromatographed on silica gel (CH2Cl2-MeOH-28% NH4OH, 95:5:0.5 then 9:1:0.05) to give 2-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-propane-1,3-diol (0.188 g, 77%) as a colourless solid. 1H NMR (CD3OD) δ 8.42, (s, 1H), 7.65 (s, 1H), 7.25-7.16 (m, 5H), 5.75 (s, 2H), 4.50 (s, 2H), 4.10 (s, 3H), 4.03 (s, 2H), 3.68 (dd, J=11.2, 5.9 Hz, 2H), 3.58 (dd, J=11.2, 5.9 Hz, 2H), 2.81 (pentet, J=5.6 Hz, 1H). 13C NMR (CD3OD, 75.5 MHz, referenced to centre line of CD3OD at δ 49.0) δ 157.9, 150.8, 150.6, 138.7, 134.1, 129.3, 128.8, 128.6, 117.0, 116.2, 78.5, 71.5, 62.5 (CH2X2), 61.3, 54.3, 41.4. +ESMS Found 373.1865 (M+H)+ C19H25N4O4 requires 373.1876.

Workup

  1. custom0.196 g, 0.659 mmol, prepared as in G
  2. customThe solvent was evaporated
  3. customthe residue chromatographed on silica gel (CH2Cl2-MeOH-28% NH4OH, 95:5:0.5

Sources & evidence

ORD record
ord-119f2aba548e49fb8f56bc40c5ba70d2
Source dataset
uspto-grants-2014_10
Patent number
US08853224B2

Reaction notes

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