Acetic Acid → HCID 178484167, compound

HRID 511670Notes

Reaction equation

HRID 511670 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:11][O:10][CH2:9]2)=[CH:4][C:3]=1[NH:12][C:13](=O)[CH2:14][CH2:15][CH:16]1[CH2:19][CH:18]([N:20]([CH2:22][C@@H:23]2[C@@H:30]3[C@@H:26]([O:27][C:28]([CH3:32])([CH3:31])[O:29]3)[C@H:25]([N:33]3[CH:41]=[N:40][C:39]4[C:34]3=[N:35][CH:36]=[N:37][C:38]=4[NH2:42])[O:24]2)[CH3:21])[CH2:17]1.C(O)(=O)C>C(Cl)Cl>[CH3:31][C:28]1([CH3:32])[O:29][C@@H:30]2[C@@H:23]([CH2:22][N:20]([CH3:21])[CH:18]3[CH2:17][CH:16]([CH2:15][CH2:14][C:13]4[NH:1][C:2]5[CH:7]=[CH:6][C:5]([CH:8]6[CH2:9][O:10][CH2:11]6)=[CH:4][C:3]=5[N:12]=4)[CH2:19]3)[O:24][C@@H:25]([N:33]3[CH:41]=[N:40][C:39]4[C:34]3=[N:35][CH:36]=[N:37][C:38]=4[NH2:42])[C@@H:26]2[O:27]1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 67775354N-(2-amino-5-(oxetan-3-yl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanamide

Product 1

HCID 178484167HCID 178484167, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

N-(2-amino-5-(oxetan-3-yl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanamide (0.446 g, 0.752 mmol) was taken up in acetic acid (7.7 mL, 140 mmol) and heated at 65° C. for 3.5 h; HPLC/LC MS indicated complete conversion. At 3.75 h the acetic acid was removed by distillation with minimal warming to afford an orange oil, which was taken up in CH2Cl2 (45 mL) and washed with saturated aqueous NaHCO3 (2×30 mL). The aqueous layer was treated with NaCl until saturated and extracted with CH2Cl2 (2×20 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo to afford a light orange oil. Purification by column chromatography (2×8 cm silica; 0-5% 7 N methanolic NH3/CH2Cl2) afforded the title compound (0.28 g, 65%) as a light orange foam: MS (ESI+) for C30H38N8O4 m/z 575.3 (M+H)+; MS (ESI−) for C30H38N8O4 m/z 573.3 (M−H)−; HPLC purity >95% (ret. time 2.142 min).

Workup

  1. customAt 3.75 h the acetic acid was removed by distillation
  2. temperaturewith minimal warming
  3. customto afford an orange oil, which
  4. washwashed with saturated aqueous NaHCO3 (2×30 mL)
  5. additionThe aqueous layer was treated with NaCl until saturated and
  6. extractionextracted with CH2Cl2 (2×20 mL)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto afford a light orange oil
  10. customPurification by column chromatography (2×8 cm silica; 0-5% 7 N methanolic NH3/CH2Cl2)

Sources & evidence

ORD record
ord-ccba1657dc2f42c99c6da69a5283a4da
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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