2-(1-((4-Morpholino-2-(tributylstannyl)pyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol → 2-(1-((2-(1H-indazol-3-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 2091885Notes

Reaction equation

HRID 2091885 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:29]=[C:28]([CH2:30][N:31]4[CH2:36][CH2:35][CH:34]([C:37]([OH:40])([CH3:39])[CH3:38])[CH2:33][CH2:32]4)[CH:27]=[CH:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:3][CH2:2]1.I[C:42]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[NH:44][N:43]=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:44]1[C:45]2[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:42]([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:29]=[C:28]([CH2:30][N:31]4[CH2:32][CH2:33][CH:34]([C:37]([OH:40])([CH3:38])[CH3:39])[CH2:35][CH2:36]4)[CH:27]=[CH:26][C:9]=3[N:10]=2)=[N:43]1

Participants

6

Reactant 2

HCID 584049802-(1-((4-Morpholino-2-(tributylstannyl)pyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-olHCID 178506566HCID 178506566, compound

Product 1

HCID 533786782-(1-((2-(1H-indazol-3-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol

Reagents, catalysts & solvents 3

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

Procedure

To a degassed solution of 2-(1-((4-morpholino-2-(tributylstannyl)pyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol from Example 136 (0.15 g) and 3-iodo-1H-indazole (1.4 eq) in 1,4-dioxane (1.4 mL) was added Copper(I) thiophene-2-carboxylate (1 eq) and Tetrakis(triphenylphosphine)palladium(0) (0.125 eq). The reaction was microwaved at 140° C. for 30 minutes and then loaded onto biotage isolute scx-2 catridge and eluted with 2M ammonia in Methanol. The crude material was purified by reverse phase HPLC to afford 23.4 mg of 138. MS (Q1) 488.3 (M)+

Workup

  1. customThe reaction was microwaved at 140° C. for 30 minutes
  2. washeluted with 2M ammonia in Methanol
  3. customThe crude material was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-22cfd4a3cc9747158287c87da8dc043a
Source dataset
uspto-grants-2013_05
Patent number
US08440651B2

Reaction notes

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