N-Methylbenzylamine → 3-{6-[6-(N-Benzyl-N-methyl-amino)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy}-isoxazole-5-carboxylic acid methyl ester

HRID 549778Notes

Reaction equation

HRID 549778 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:9][N:8]=[C:7]([O:10][CH2:11][CH:12]2[CH:19]3[CH:15]([O:16][C:17]([CH3:21])([CH3:20])[O:18]3)[CH:14]([N:22]3[CH:30]=[N:29][C:28]4[C:23]3=[N:24][CH:25]=[N:26][C:27]=4Cl)[O:13]2)[CH:6]=1)=[O:4].C(N(C(C)C)CC)(C)C.[CH3:41][NH:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[O:9][N:8]=[C:7]([O:10][CH2:11][CH:12]2[CH:19]3[CH:15]([O:16][C:17]([CH3:21])([CH3:20])[O:18]3)[CH:14]([N:22]3[CH:30]=[N:29][C:28]4[C:23]3=[N:24][CH:25]=[N:26][C:27]=4[N:42]([CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH3:41])[O:13]2)[CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 7669N-MethylbenzylamineHCID 81531Diisopropylethylamine2×HCID 865997133-[6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy]isoxazole-5-carboxylic acid methyl ester

Product 1

HCID 671505443-{6-[6-(N-Benzyl-N-methyl-amino)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy}-isoxazole-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy]-isoxazole-5-carboxylic acid methyl ester (0.106 g, 0.23 mmol) in tetrahydrofuran (1.2 mL) was added polymer-bound diisopropylethylamine (PS-DIEA; Argonaut Tech., 3.83 mmol/g, 0.190 g, 3 eq), followed by addition of 0.040 mL of N-methyl-N-benzylamine (1.2 eq). The resulting mixture was stirred at room temperature overnight. The PS-DIEA resin was washed three times with dichloromethane and the solution obtained from the washes was concentrated to yield 3-{6-[6-(N-Benzyl-N-methyl-amino)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy}-isoxazole-5-carboxylic acid methyl ester as yellow oil. This material (0.23 mmol) was dissolved in 1,4-dioxane (1.2 mL) and 0.250 mL of an aqueous 2M lithium hydroxide solution added. The mixture was stirred at room temperature for 4 h. The crude product, isolated after acid workup, was used without further purification in the following step. MW calculated for C25H26N6O7 (MH+): 523. found 523 by LCMS.

Workup

  1. washThe PS-DIEA resin was washed three times with dichloromethane
  2. customthe solution obtained from the washes
  3. concentrationwas concentrated

Sources & evidence

ORD record
ord-6473786a1bf94d14b4c83a31603b8d74
Source dataset
uspto-grants-2011_05
Patent number
US07943760B2

Reaction notes

Loading…