Ethyl orthoformate → HCID 18651641, compound

HRID 420885Notes

Reaction equation

HRID 420885 reaction equation
Cl[C:2]1[C:7]([NH:8][CH:9]=O)=[C:6]([NH:11][C@@H:12]2[CH2:16][C@H:15]([CH2:17][OH:18])[CH:14]=[CH:13]2)[N:5]=[C:4]([NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[N:3]=1.C(O)(C)C.Cl.C(OCC)(OCC)OCC.C([O-])(O)=O.[Na+].[CH:45]1([NH2:48])[CH2:47][CH2:46]1>>[CH:45]1([NH:48][C:2]2[N:3]=[C:4]([NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[N:5]=[C:6]3[C:7]=2[N:8]=[CH:9][N:11]3[C@@H:12]2[CH2:16][C@H:15]([CH2:17][OH:18])[CH:14]=[CH:13]2)[CH2:47][CH2:46]1

Participants

6

Reactant 5

HCID 31214Ethyl orthoformateHCID 69828CyclopropylamineHCID 516892Sodium Bicarbonate2×HCID 21912024Isopropanol hydrochlorideHCID 22842363HCID 22842363, compound

Product 1

HCID 18651641HCID 18651641, compoundYield 73%

Conditions

Temperature
41 °C

Procedure

Under nitrogen atmosphere, N-{4-chloro-5-formamido-6-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enylamino]pyrimidin-2-yl}isobutyramide (15 mg, 42.4 mmol) was dissolved in an anhydrous solution of isopropanol/HCl 1 N (254 ml, 254.4 mmol) and heated to 40-42° C. for 3.5 h. The solution was cooled to 5/10° C. and triethyl orthoformate (21 ml, 127.2 mmol) was added. The resulting mixture was stirred for 2 h at 5-10° C. NaHCO3 (21.37 g, 254.4 mmol) was added slowly, stirred 30 min and the salts were filtered off. To the resulting clear solution, NaHCO3 (3.56 g, 42.4 mmol) and cyclopropylamine (14.7 ml, 212 mmol) were added, the mixture was refluxed for 1 h and the salts were filtered off. The solution was evaporated and the syrup was dissolved in hot isopropanol (120 ml). This mixture was cooled to 0-2° C. and the resulting slurry filtered off. The solid was dried under vacuum at 30° C. There was obtained 10.97 g (73%) of (−)-N-{6-(cyclopropylamino)-9-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enyl]-9H-purin-2-yl}isobutyramide as a white powder. HPLC analysis: 95.0%+3.8% Abacavir.

Workup

  1. additionwas added
  2. stirringstirred 30 min
  3. filtrationthe salts were filtered off
  4. temperaturethe mixture was refluxed for 1 h
  5. filtrationthe salts were filtered off
  6. customThe solution was evaporated
  7. dissolutionthe syrup was dissolved in hot isopropanol (120 ml)
  8. temperatureThis mixture was cooled to 0-2° C.
  9. filtrationthe resulting slurry filtered off
  10. customThe solid was dried under vacuum at 30° C

Sources & evidence

ORD record
ord-ccc08073bb60411099df22085f6e2546
Source dataset
uspto-grants-2012_01
Patent number
US08097723B2

Reaction notes

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