HCID 59605344, compound → HCID 59605437, compound

HRID 1945732Notes

Reaction equation

HRID 1945732 reaction equation
C1(S([N:10]2[C:14]3=[CH:15][N:16]=[CH:17][C:18]([C:19]4[N:20]=[C:21]([N:41]5[CH2:46][CH2:45][O:44][CH2:43][CH2:42]5)[C:22]5[S:27][C:26]([CH2:28][N:29]6[CH2:34][CH2:33][N:32]([C:35]([CH3:40])([CH3:39])[C:36]([NH2:38])=[O:37])[CH2:31][CH2:30]6)=[CH:25][C:23]=5[N:24]=4)=[C:13]3[CH:12]=[C:11]2[CH3:47])(=O)=O)C=CC=CC=1>O1CCOCC1.[OH-].[Na+]>[CH3:40][C:35]([N:32]1[CH2:31][CH2:30][N:29]([CH2:28][C:26]2[S:27][C:22]3[C:21]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)=[N:20][C:19]([C:18]4[CH:17]=[N:16][CH:15]=[C:14]5[NH:10][C:11]([CH3:47])=[CH:12][C:13]=45)=[N:24][C:23]=3[CH:25]=2)[CH2:34][CH2:33]1)([CH3:39])[C:36]([NH2:38])=[O:37]

Participants

4

Reactant 1

HCID 59605344HCID 59605344, compound

Product 1

HCID 59605437HCID 59605437, compoundYield 35.2%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A 25 mL round-bottomed flask, under nitrogen, fitted with a condenser/inert gas bubbler (via a Claisen head), was charged with a solution of 2-{4-[2-(1-benzenesulfonyl-2-methyl-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]piperazine-1-yl}isobutyramide (0.17 g, 0.25 mmol) in dioxane (4 mL), IMS (4 mL) and NaOH 12.5M (0.4 mL). The resulting mixture was stirred at room temperature for 2.5 h. The solution was concentrated in vacuo, the residue diluted with MeOH and loaded onto a Isolute® SCX-2 cartridge treated with MeOH. The cartridge was washed with MeOH (100 mL) and the product was recovered eluting with 2N NH3 in MeOH, the eluent concentrated, suspended in dioxane/water and freeze-dried overnight. The resultant solid was dissolved in DMSO and purified by preparative HPLC (C18 column) gradient: (acetonitrile/20 mM triethylamine) 10% to 98% in (water/20 mM triethylamine) over 20 min (flow rate 18 ml/min). The product was freeze-dried overnight yielding 142 as a white powder (0.047 g, 35%). LCMS (Method E): RT=5.27 min, [M+H]+ 535.2. 1H NMR (DMSO, 400 MHz): δ 11.43 (s, 1 H); 8.22 (d, J=5.4 Hz, 1 H); 7.43 (s, 1 H); 7.33 (dd, J=6.3, 0.9 Hz, 1 H); 7.07 (d, J=3.5 Hz, 1 H); 6.95 (d, J=3.45 Hz, 1 H); 6.87 (s, 1 H); 3.98 (t, J=4.6 Hz, 4 H); 3.87 (s, 2 H); 3.81 (t, J=4.6 Hz, 4 H); 3.57 (s, 3 H); 2.61-2.53 (m, 2 H); 2.49-2.45 (m, 2 H); 2.44 (s, 4 H); 1.08 (s, 6 H)

Workup

  1. customA 25 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. additionthe residue diluted with MeOH
  4. additiontreated with MeOH
  5. washThe cartridge was washed with MeOH (100 mL)
  6. customthe product was recovered
  7. washeluting with 2N NH3 in MeOH
  8. concentrationthe eluent concentrated
  9. customfreeze-dried overnight
  10. dissolutionThe resultant solid was dissolved in DMSO
  11. custompurified by preparative HPLC (C18 column) gradient
  12. wait(acetonitrile/20 mM triethylamine) 10% to 98% in (water/20 mM triethylamine) over 20 min (flow rate 18 ml/min)
  13. customThe product was freeze-dried overnight

Sources & evidence

ORD record
ord-9fd1f74830194450addbee2124821b94
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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