2-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide → 2-(4-((2-(Imidazo[1,5-a]pyridin-8-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide

HRID 1922962Notes

Reaction equation

HRID 1922962 reaction equation
[N:1]1([C:7]2[C:8]3[S: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)=[CH: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.Br[C:43]1[C:44]2[N:45]([CH:49]=[N:50][CH:51]=2)[CH:46]=[CH:47][CH:48]=1>O1CCOCC1.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.S1C=CC=C1C([O-])=O.[Cu+]>[CH:51]1[N:50]=[CH:49][N:45]2[CH:46]=[CH:47][CH:48]=[C:43]([C:11]3[N:12]=[C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[C:8]4[S:28][C:27]([CH2:29][N:30]5[CH2:35][CH2:34][N:33]([C:36]([CH3:40])([CH3:41])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]5)=[CH:26][C:9]=4[N:10]=3)[C:44]=12

Participants

6

Reactant 2

HCID 575067302-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramideHCID 594686818-Bromoimidazo[1,5-a]pyridine

Product 1

HCID 498347592-(4-((2-(Imidazo[1,5-a]pyridin-8-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamideYield 73%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
150 °C

Procedure

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide (132 mg, 0.19 mmol), 8-bromoimidazo[1,5-a]pyridine (45 mg, 0.23 mmol), Pd(PPh3)4 (22 mg, 0.02 mmol) and copper(I) thiophene-2-carboxylate (7 mg, 0.04 mmol) in dioxane (2 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give 202 as a yellow solid (72 mg, 73%). LCMS (Method G): RT 5.12 min; [M+H]+ 521. 1H NMR (400 MHz, CHCl3-d): δ 8.33 (s, 1 H); 8.21 (s, 1 H); 8.04 (d, J=6.9 Hz, 1 H); 7.93 (d, J=6.9 Hz, 1 H); 7.36 (s, 1 H); 7.07 (m, 1 H); 6.74-6.69 (m, 1 H); 5.19 (s, 1 H); 4.07 (t, J=4.7 Hz, 4 H); 3.96-3.86 (m, 4 H); 3.88-3.83 (m, 2 H); 2.61 (s, 8 H); 1.25 (s, 6 H)

Workup

  1. customwas purged with argon gas
  2. washThe cartridge was washed with MeOH
  3. washthe desired product eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-609806445f954c4da79798e9d1c65c4b
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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