HCID 59605558, compound → HCID 59606157, compound

HRID 1945752Notes

Reaction equation

HRID 1945752 reaction equation
C1(S([N:10]2[C:14]3=[CH:15][N:16]=[CH:17][C:18]([C:19]4[N:27]=[C:26]5[C:22]([N:23]=[C:24]([CH2:29][N:30]6[CH2:35][CH2:34][CH:33]([C:36]([OH:39])([CH3:38])[CH3:37])[CH2:32][CH2:31]6)[N:25]5[CH3:28])=[C:21]([N:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)[N:20]=4)=[C:13]3[CH:12]=[C:11]2[CH3:46])(=O)=O)C=CC=CC=1>O1CCOCC1.[OH-].[Na+]>[CH3:28][N:25]1[C:24]([CH2:29][N:30]2[CH2:31][CH2:32][CH:33]([C:36]([OH:39])([CH3:38])[CH3:37])[CH2:34][CH2:35]2)=[N:23][C:22]2[C:26]1=[N:27][C:19]([C:18]1[CH:17]=[N:16][CH:15]=[C:14]3[NH:10][C:11]([CH3:46])=[CH:12][C:13]=13)=[N:20][C:21]=2[N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1

Participants

4

Reactant 1

HCID 59605558HCID 59605558, compound

Product 1

HCID 59606157HCID 59606157, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A 50 mL round-bottomed flask, under nitrogen, fitted with a condenser/inert gas bubbler (via a Claisen head), was charged with a solution of 2-{1-[2-(1-benzenesulfonyl-2-methyl-1H-pyrrolo[2,3-c]pyridin-4-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-ol (0.41 g, 0.64 mmol) in dioxane (8 mL), IMS (8 mL) and NaOH 12.5M (0.8 mL). The resulting mixture was stirred at room temperature for 2 h. The solution was concentrated in vacuo, the residue was dissolved in DCM and a fine solid was removed by filtration through a Celite pad. The solution was purified by flash chromatography (Si—PCC; 25 g SiO2 column, 0% to 20% MeOH in DCM). The residue was then purified further by preparative HPLC [(C18 column) gradient: (acetonitrile/20 mM triethylamine) 30% to 98% in (water/20 mM triethylamine) over 20 min (flow rate 18 ml/min)]. The product was freeze-dried overnight yielding 165 as a white powder (0.136 g, 43%). LCMS (method E): RT=4.89 min, [M+H]+ 505.24. 1H NMR (CDCl3, 400 MHz) δ 9.28 (s, 1 H), 8.70 (s, 1 H), 8.30 (s, 1 H), 4.40 (m, 4 H), 3.96 (s, 3 H), 3.89 (m, 4 H), 3.74 (s, 2 H), 2.96 (m, 2 H), 2.58 (s, 3 H), 2.10 (m, 2 H), 1.75 (m, 2 H), 1.40-1.28 (m, 3 H), 1.18 (s, 6 H)

Workup

  1. customA 50 mL round-bottomed flask, under nitrogen, fitted with a condenser/inert gas bubbler (via a Claisen head),
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionthe residue was dissolved in DCM
  4. customa fine solid was removed by filtration through a Celite pad
  5. customThe solution was purified by flash chromatography (Si—PCC; 25 g SiO2 column, 0% to 20% MeOH in DCM)
  6. customThe residue was then purified further by preparative HPLC [(C18 column) gradient: (acetonitrile/20 mM triethylamine) 30% to 98% in (water/20 mM triethylamine) over 20 min (flow rate 18 ml/min)]
  7. customThe product was freeze-dried overnight

Sources & evidence

ORD record
ord-5577bf0b22c345ff987ad53630ce1673
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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