Sodium Hydroxide → HCID 49787177, compound

HRID 1692882Notes

Reaction equation

HRID 1692882 reaction equation
[OH-].[Na+].C1(S([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([C:21]3[N:22]=[C:23]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[C:24]4[N:29]=[C:28]([CH2:30][N:31]5[CH2:34][CH:33]([N:35]6[CH2:40][CH2:39][O:38][CH2:37][CH2:36]6)[CH2:32]5)[S:27][C:25]=4[N:26]=3)=[CH:13]2)(=O)=O)C=CC=CC=1>O1CCOCC1>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([C:21]2[N:22]=[C:23]([N:41]3[CH2:42][CH2:43][O:44][CH2:45][CH2:46]3)[C:24]3[N:29]=[C:28]([CH2:30][N:31]4[CH2:32][CH:33]([N:35]5[CH2:36][CH2:37][O:38][CH2:39][CH2:40]5)[CH2:34]4)[S:27][C:25]=3[N:26]=2)=[CH:13]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67279553HCID 67279553, compound

Product 1

HCID 49787177HCID 49787177, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A degassed solution of 5-chloro-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)thiazolo[5,4-c]pyrimidine (210 mg, 0.51 mmol), 1-(phenylsulfonyl)-3-indoleboronic acid (231 mg, 0.77 mmol), Pd(PPh3)4 (60 mg, 0.052 mmol) and Cs2CO3 (332 mg, 1.03 mmol) in a mixture of 1,4-dioxane (8 mL) and water (4 mL) was subjected to microwave irradiation at 150° C. for 30 min. 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 eluent was collected and concentrated to give 5-(1-benzenesulfonyl-1H-indol-3-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[5,4-c]pyrimidine as a crude oil. Aqueous NaOH (12.5 M, 0.6 mL) was added to a solution 5-(1-benzenesulfonyl-1H-indol-3-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)thiazolo[5,4-d]pyrimidine in 1,4-dioxane (6 mL) and IMS (6 mL). The reaction mixture was stirred at ambient temperature for 1 h, then concentrated in vacuo. The resultant 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 eluent was collected and concentrated to afford a sticky solid. The solid was purified by flash chromatography (Si-PPC, DCM: MeOH, 100:0 to 98:2 to 95:5) followed by trituration from hot MeOH to afford 117 as a tan solid (117 mg, 47%). LCMS (Method E): RT=7.47 min, [M+H]+ 492.2. 1H NMR (CDCl3, 400 MHz): δ 8.65-8.60 (m, 1H); 8.44 (s, 1H); 8.13 (d, J=2.8 Hz, 1H); 7.44-7.39 (m, 1H); 7.31-7.25 (m, 2H); 4.43 (t, J=4.6 Hz, 4H); 3.99 (s, 2H); 3.91 (t, J=4.7 Hz, 4H); 3.73 (t, J=4.5 Hz, 4H); 3.66 (t, J=5.8 Hz, 2H); 3.18-3.07 (m, 3H); 2.40-2.31 (m, 4H)

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in MeOH
  3. washThe cartridge was then washed with MeOH
  4. washthe desired product was subsequently eluted
  5. customThe eluent was collected
  6. concentrationconcentrated
  7. customto afford a sticky solid
  8. customThe solid was purified by flash chromatography (Si-PPC, DCM: MeOH, 100:0 to 98:2 to 95:5)

Sources & evidence

ORD record
ord-73d8be4304e042f18128f6c107857b22
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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