HCID 57506731, compound → HCID 67492555, compound

HRID 1922930Notes

Reaction equation

HRID 1922930 reaction equation
[N:1]1([C:7]2[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:35][CH2:34][N:33]([C:36]([CH3:41])([CH3:40])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]4)[S:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:42]1([S:48]([N:51]2[C:59]3[CH:58]=[CH:57][N:56]=[C:55](Br)[C:54]=3[CH:53]=[CH:52]2)(=[O:50])=[O:49])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+]>[C:42]1([S:48]([N:51]2[C:59]3[CH:58]=[CH:57][N:56]=[C:55]([C:11]4[N:12]=[C:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[C:8]5[N:28]=[C:27]([CH2:29][N:30]6[CH2:35][CH2:34][N:33]([C:36]([CH3:40])([CH3:41])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]6)[S:26][C:9]=5[N:10]=4)[C:54]=3[CH:53]=[CH:52]2)(=[O:50])=[O:49])[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

5

Reactant 2

HCID 57506731HCID 57506731, compoundHCID 596034392-[4-(7-Morpholin-4-yl-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide

Product 1

HCID 67492555HCID 67492555, compound

Reagents, catalysts & solvents 2

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A degassed solution of 2-[4-(7-morpholin-4-yl-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide (250 mg, 0.36 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (130 mg, 0.39 mmol), PdCl2{PtBu2(Ph-p-Nme2)}2 (26 mg, 0.036 mmol) and copper(I) thiophene-2-carboxylate (14 mg, 0.07 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 2-{4-[5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl]piperazin-1-yl}isobutyramide as a crude oil. Aqueous NaOH (12.5 M, 0 4 mL) was added to a solution of 2-{4-[5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidin-2-ylmethyl]-piperazin-1-yl}isobutyramide 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) followed by reversed phase HPLC (Phenomenex Luna C-18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 95:5 to 2:98) to afford 169 as a yellow solid (43 mg, 23%). LCMS (method E): RT=5.03 min, [M+H]+=522.2. 1H NMR (CDCl3, 400 MHz) δ 8.55 (d, J=5.6 Hz, 1 H), 7.45-7.40 (m, 2 H), 7.38 (d, J=3.3 Hz, 1 H), 7.11 (d, J=5.3 Hz, 1 H), 5.25 (d, J=5.3 Hz, 1 H), 4.53-4.42 (m, 4 H), 3.90 (m, 6 H), 2.68 (m, 4 H), 2.62 (m, 4 H), 1.25 (s, 6 H)

Workup

  1. customirradiation at 140° C. for 20 minutes
  2. washThe cartridge was then washed with MeOH
  3. washthe desired product was subsequently eluted
  4. customThe product was collected
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-fcb7f731b3eb41799bfef142e9494f1d
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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