Methanol → Carbonic acid 6-amino-9-benzyl-2-(2-methoxy-ethoxy)-9H-purin-8-yl ester ethyl ester

HRID 1662962Notes

Reaction equation

HRID 1662962 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([OH:23])[N:6]2[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C.Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35].CO>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:37]([O:36][C:34](=[O:35])[O:23][C:5]1[N:6]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:7]2[C:3]([N:4]=1)=[C:2]([NH2:1])[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=2)[CH3:38]

Participants

7

Reactant 4

HCID 887MethanolHCID 10928Ethyl chloroformate2×HCID 81531DiisopropylethylamineHCID 178496186HCID 178496186, compound

Product 1

HCID 11280653Carbonic acid 6-amino-9-benzyl-2-(2-methoxy-ethoxy)-9H-purin-8-yl ester ethyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

6-Amino-9-benzyl-2-(2-methoxy-ethoxy)-9H-purin-8-ol, 29 (11.75 mg, 0.027 mmol, prepared according to the procedure described by Kurimota, et al., Bioorg. Med. Chem., 12, 1091-109 (2004) was suspended in CH2Cl2 (0.6 mL) and cooled to 0° C. DIEA (11.96 μL, 0.068 mmol) and ethyl chloroformate (3.86 mg, 0.036 mmol, added as a 10% by volume solution in dichloromethane) were then added to the suspension. The reaction mixture was stirred at 0° C. for 10 minutes then allowed to warm to room temperature for 15 minutes. TLC of the reaction mixture shows that starting material remained. The reaction mixture was heated to 35° C., DMAP (cat.), methanol (60 μL portions) was added to dissolve 29, and additional aliquots of ethyl chloroformate (3.86 mg, 0.036 mmol, added as a 10% by volume solution in dichloromethane) were added until the reactions was complete. The crude mixture was purified by flash chromatography using a 0 to 100% gradient of ethyl acetate in hexane. The desired peaks were collected and concentrated in-vacuo to yield 8.5 mg (80%) of compound 51 as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J=Hz, 2H), 7.27 (m, 3H), 4.98 (s, 2H), 4.46 (m, 4H), 3.74 (m, 2H), 3.42 (s, 2H), 1.46 (t, 3H); MS [M+H]+ m/z 388.3.

Workup

  1. additionwere then added to the suspension
  2. temperatureto warm to room temperature for 15 minutes
  3. temperatureThe reaction mixture was heated to 35° C.
  4. additionwere added until the reactions
  5. customThe crude mixture was purified by flash chromatography
  6. customThe desired peaks were collected
  7. concentrationconcentrated in-vacuo

Sources & evidence

ORD record
ord-d88fe7a086694fad830ed7ad06583e0a
Source dataset
uspto-grants-2011_10
Patent number
US08034802B2

Reaction notes

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