2-(1-((7-Morpholino-5-(tributylstannyl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol → 2-(1-((5-(1H-indazol-3-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1945787Notes

Reaction equation

HRID 1945787 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:35][CH2:34][CH:33]([C:36]([OH:39])([CH3:38])[CH3:37])[CH2:32][CH2:31]4)[S:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:3][CH2:2]1.I[C:41]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[NH:43][N:42]=1>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:43]1[C:44]2[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:41]([C:11]2[N:12]=[C:7]([N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:35][CH2:34][CH:33]([C:36]([OH:39])([CH3:38])[CH3:37])[CH2:32][CH2:31]4)[S:26][C:9]=3[N:10]=2)=[N:42]1

Participants

6

Reactant 2

HCID 596055632-(1-((7-Morpholino-5-(tributylstannyl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-olHCID 178506566HCID 178506566, compound

Product 1

HCID 498322742-(1-((5-(1H-indazol-3-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-olYield 28%

Reagents, catalysts & solvents 3

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-(1-((7-morpholino-5-(tributylstannyl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol (0.211 g, 0.32 mmol), 3-iodo-1H-indazole (0.116 g, 0.48 mmol), copper(I) 2-thiophene carboxylate (0.012 g, 0.064 mmol) and Pd(PPh3)4 (0.037 g, 0.032 mmol) in dioxane (3 mL)was subjected to microwave irradiation at 150° C. for 90 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The eluent was concentrated in vacuo and the resultant residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give 209 as a yellow solid (0.043 g, 28%). LCMS (Method G): RT=7.71 min, [M+H]+ 494.3. 1H NMR (400 MHz, DMSO-d6): δ 13.45 (s, 1 H); 8.48 (d, J=8.3 Hz, 1 H); 7.61 (d, J=8.3 Hz, 1 H); 7.41 (t, J=7.6 Hz, 1 H); 7.26 (t, J=7.6 Hz, 1 H); 4.37 (m, 4 H); 3.88 (s, 2 H); 3.82 (t, J=4.6 Hz, 4 H); 3.02 (d, J=11.0 Hz, 2 H); 2.12 (t, J=11.0 Hz, 2 H); 1.74-1.69 (m, 2 H); 1.36-1.28 (m, 2 H); 1.26-1.23 (m, 2 H); 1.06 (s, 6 H)

Workup

  1. customirradiation at 150° C. for 90 min
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted
  4. concentrationThe eluent was concentrated in vacuo
  5. customthe resultant residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-db1eecbcca7149ec8620750d9129cedf
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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