Trifluoroacetic acid → HCID 67951397, compound

HRID 1054556Notes

Reaction equation

HRID 1054556 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C@H:18]1[C@@H:22]2[O:23]C(C)(C)[O:25][C@@H:21]2[C@@H:20]([CH2:28][N:29]([CH3:47])[CH2:30][CH2:31][CH2:32][NH:33][C:34]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]([CH3:46])([CH3:45])[CH3:44])=[CH:39][CH:38]=2)=[O:35])[CH2:19]1>O>[NH2:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C@@H:18]1[CH2:19][C@H:20]([CH2:28][N:29]([CH3:47])[CH2:30][CH2:31][CH2:32][NH:33][C:34]([NH:36][C:37]2[CH:38]=[CH:39][C:40]([C:43]([CH3:45])([CH3:46])[CH3:44])=[CH:41][CH:42]=2)=[O:35])[C@@H:21]([OH:25])[C@H:22]1[OH:23]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67818076HCID 67818076, compound

Product 1

HCID 67951397HCID 67951397, compoundYield 103.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A cooled (ice bath) solution of trifluoroacetic acid (5.2 mL, 67 mmol) in water (0.60 mL) was added to the precooled (ice bath) flask of 1-(3-((((3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea (0.10 g, 0.18 mmol). The reaction mixture was stirred for 30 min, the cold bath was removed, and the clear, pale yellow reaction mixture was stirred at rt for 1 h; HPLC indicated complete consumption of starting material. The reaction mixture was concentrated in vacuo and diluted with MeOH and concentrated (2×10 mL). The resultant residue was taken up in 10% MeOH/CH2Cl2 (60 mL) and washed with 10% aqueous NH4OH (1×18 mL). The separated aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×18 mL) and the cloudy combined organics (pH>7) were diluted with MeOH (5 mL) to afford a clear solution, which was dried (Na2SO4) and concentrated in vacuo to afford the title compound (95 mg, quant) as a slightly off-white gum/foam: MS (ESI+) for C26H38N8O3 m/z 511.4 [M+H]+; MS (ESI−) for C26H38N8O3 m/z 509.3 [M−H]−, 555.3 [M+CO2H]−; HPLC purity>95% (ret. time, 2.701 min); 1H NMR (400 MHz, d4-MeOH) δ 8.17 (s, 1H), 8.16 (s, 1H), 7.27-7.20 (m, 4H), 4.78 (dt, J=10.7, 8.14 Hz, 1H), 4.52 (dd, J=8.5, 6.01 Hz, 1H), 4.01 (dd, J=5.8, 4.15 Hz, 1H), 3.31-3.23 (m, 2H), 2.78-2.70 (m, 1H), 2.67-2.55 (m, 3H), 2.48-2.31 (m, 2H), 2.39 (bs, 3H), 1.95-1.87 (m, 1H), 1.81-1.74 (m, 2H), 1.28 (s, 9H).

Workup

  1. customthe cold bath was removed
  2. stirringthe clear, pale yellow reaction mixture was stirred at rt for 1 h
  3. customconsumption of starting material
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. additiondiluted with MeOH
  6. concentrationconcentrated (2×10 mL)
  7. washwashed with 10% aqueous NH4OH (1×18 mL)
  8. extractionThe separated aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×18 mL)
  9. additionwere diluted with MeOH (5 mL)
  10. customto afford a clear solution, which
  11. dry with materialwas dried (Na2SO4)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-47fbfd26f13e45db89f89423c42fd30a
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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