Hydrochloric Acid → (1S,4R)-4-(2-Amino-chloro-9-H-purin-9-yl)-2-cyclopentene-1-methanol Hydrochloride

HRID 985141Notes

Reaction equation

HRID 985141 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:13][C@H:12]([CH2:14][OH:15])[CH:11]=[CH:10]2)[C:5]([NH:16][CH:17]=O)=[C:4]([Cl:19])[N:3]=1.C(OC(OCC)OCC)C.[ClH:30]>CO.[OH-].[Na+]>[ClH:19].[NH2:1][C:2]1[N:7]=[C:6]2[C:5]([N:16]=[C:17]([Cl:30])[N:8]2[C@@H:9]2[CH2:13][C@H:12]([CH2:14][OH:15])[CH:11]=[CH:10]2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 31214Ethyl orthoformateHCID 9795791HCID 9795791, compound

Product 1

HCID 86586433(1S,4R)-4-(2-Amino-chloro-9-H-purin-9-yl)-2-cyclopentene-1-methanol HydrochlorideYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of (1S,4R)-4-[(2-amino-6-chloro-5-formamido-4-pyrimidinyl)amino]-2-cyclopentene-1-methanol (Example 7, 1.00 g, 3.50 mmol) and triethylorthoformate (Aldrich, Sure Seal, 18 mL) was stirred while concentrated hydrochloric acid (37%, 1.25 mL) was added in one portion. The resulting clear, colorless solution was stirred under nitrogen. A white precipitate began to form after 15 minutes. After 4 hours, TLC of a drop of the reaction mixture dissolved in methanol and neutralized with sodium hydroxide (silica gel plates developed in 10% methanol-chloroform, visualized in UV light) showed almost complete conversion of VIa to a higher-Rf material The precipitate was filtered, washed with t-butyl methyl ether (15 mL) and dried at 0.2 mm Hg/25° C. for 18 hours to give the title compound as a white powder (975 mg, 92%), m.p. >300° C. dec.; mass spectrum (CI/CH4): 266 (M+1); 1H-NMR (DMSO-d6)δ: 8.18 (s, 1, purine CH), 7.2-6.7 (br s, NH2, OH overlapped by water), 6.20 and 5.90 (both m, 1 each, CH═CH), 5.48 (m, 1, NCH), 3.47 (d, J=5.7 Hz, 2, CH2O), 2.90 (m, 1, CH), 2.75-2.55 and 1.75-1.60 (both m, 1 each, CH2).

Workup

  1. additionwas added in one portion
  2. customto form after 15 minutes
  3. filtrationwas filtered
  4. washwashed with t-butyl methyl ether (15 mL)
  5. customdried at 0.2 mm Hg/25° C. for 18 hours

Sources & evidence

ORD record
ord-205da97c3cda4c06917c33c4b0adee59
Source dataset
uspto-grants-2005_03
Patent number
US06870053B2

Reaction notes

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