Phosphoric Acid → HCID 67076828, compound

HRID 1675693Notes

Reaction equation

HRID 1675693 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:44][CH3:45])=[C:10]([CH2:19][NH:20][C:21](=[O:43])[C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:42])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]([CH2:39][CH2:40][OH:41])[CH3:38])=[CH:24][CH:23]=3)[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[P:46](=[O:50])([OH:49])([OH:48])[OH:47]>C(O)(C)C.O>[P:46]([OH:50])([OH:49])([OH:48])=[O:47].[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:44][CH3:45])=[C:10]([CH2:19][NH:20][C:21](=[O:43])[C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:42])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]([CH2:39][CH2:40][OH:41])[CH3:38])=[CH:24][CH:23]=3)[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 1004Phosphoric Acid2×HCID 23729488HCID 23729488, compound

Product 1

HCID 67076828HCID 67076828, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-4-({8-[(2-hydroxyethyl)(methyl)amino]octanoyl}amino)benzamide [the “free base”, 100 mg, about 0.161 mmol, as a substantially amorphous form thereof, as prepared in Example 1B (alternative preparation no. 2)] was dissolved in isopropanol (1 ml) at room temperature. Phosphoric acid (H3PO4, 85 wt % solution in water (commercially available e.g. from Aldrich), 3.95 microliters, 0.5 equivalents) was added. A gum formed, which dissolved on heating to 60° C. No precipitation occurred after cooling to ambient temperature and about 30 minutes at ambient temperature. Phosphoric acid (H3PO4, 85 wt % solution in water (commercially available e.g. from Aldrich), 3.95 microliters, 0.5 equivalents) was added. A gum formed, which did not dissolve on heating to 60° C. The reaction mixture was left to temperature cycle between 0° C. and 40° C. for about 2 days. A suspension had formed, and from this the resulting solid was isolated by filtration, washed with isopropanol (0.5 ml) and dried at 40° C. under vacuum overnight. 68.3 mg of dried solid was obtained.

Workup

  1. customA gum formed
  2. dissolutionwhich dissolved
  3. customNo precipitation
  4. temperatureafter cooling to ambient temperature and about 30 minutes at ambient temperature
  5. additionPhosphoric acid (H3PO4, 85 wt % solution in water (commercially available e.g. from Aldrich), 3.95 microliters, 0.5 equivalents) was added
  6. customA gum formed
  7. dissolutionwhich did not dissolve
  8. temperatureon heating to 60° C
  9. customA suspension had formed
  10. customfrom this the resulting solid was isolated by filtration
  11. washwashed with isopropanol (0.5 ml)
  12. customdried at 40° C. under vacuum overnight

Sources & evidence

ORD record
ord-d4f6a74064d74c1696b1108eed9818b8
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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