Sodium Hydroxide → HCID 59605353, compound

HRID 1922911Notes

Reaction equation

HRID 1922911 reaction equation
[OH-].[Na+].C1(S([N:12]2[C:20]3[CH:19]=[CH:18][N:17]=[C:16]([C:21]4[N:22]=[C:23]([N:41]5[CH2:46][CH2:45][O:44][CH2:43][CH2:42]5)[C:24]5[N:29]=[C:28]([CH2:30][N:31]6[CH2:34][CH:33]([N:35]7[CH2:40][CH2:39][O:38][CH2:37][CH2:36]7)[CH2:32]6)[S:27][C:25]=5[N:26]=4)[C:15]=3[CH:14]=[CH:13]2)(=O)=O)C=CC=CC=1>O1CCOCC1>[O:44]1[CH2:45][CH2:46][N:41]([C:23]2[C:24]3[N:29]=[C:28]([CH2:30][N:31]4[CH2:34][CH:33]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)[CH2:32]4)[S:27][C:25]=3[N:26]=[C:21]([C:16]3[C:15]4[CH:14]=[CH:13][NH:12][C:20]=4[CH:19]=[CH:18][N:17]=3)[N:22]=2)[CH2:42][CH2:43]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 674921475-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[5,4-d]pyrimidine

Product 1

HCID 59605353HCID 59605353, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A degassed solution of 7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine (200 mg, 0.30 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (132 mg, 0.39 mmol), PdCl2{PtBu2(Ph-p-Nme2)}2 (22 mg, 0.03 mmol) and copper(I) thiophene-2-carboxylate (12 mg, 0.06 mmol) in 1,4-dioxane (4 mL) was subjected to microwave irradiation at 140° C. for 20 minutes. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated to give 5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)thioazolo[5,4-d]pyrimidine as a crude oil. Aqueous NaOH (12.5 M, 0.5 mL) was added to a solution of 5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[5,4-d]pyrimidine in 1,4-dioxane (4 mL) and IMS (4 mL). The reaction mixture was stirred at ambient temperature for 45 min, then concentrated in vacuo. The residue was dissolved in MeOH then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated to afford a solid. The solid was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 96:4) to afford 152 as a yellow solid (56 mg, 38%). LCMS (Method E): RT=4.34 min, M+H +=493.2. 1H NMR (CDCl3, 400 MHz) δ 8.72 (bs, 1 H), 8.56 (d, J=5.7 Hz, 1 H), 7.41 (m, 2 H), 7.36 (d, J=3.2 Hz, 1 H), 4.49-4.44 (m, 4 H), 4.02 (s, 2 H), 3.90 (t, J=4.7 Hz, 4 H), 3.74-3.65 (m, 6 H), 3.16-3.07 (m, 3 H), 2.35 (m, 4 H)

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in MeOH
  3. washThe cartridge was then washed with MeOH
  4. washthe desired product was subsequently eluted
  5. customThe product was collected
  6. concentrationconcentrated
  7. customto afford a solid
  8. customThe solid was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 96:4)

Sources & evidence

ORD record
ord-b8274656ecae4647b74c5396a3d17edb
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…