2-(propan-2-yl)-1H-1,3-benzodiazole → (4-(2-hydroxypropan-2-yl)piperidin-1-yl)(2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methanone

HRID 2091858Notes

Reaction equation

HRID 2091858 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[N:11]=[C:10]([C:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20]([OH:23])([CH3:22])[CH3:21])[CH2:16][CH2:15]3)=[O:13])[CH:9]=[CH:8][C:6]=2[N:7]=1.[CH:30]([C:33]1[NH:37][C:36]2[CH:38]=[CH:39][CH:40]=[CH:41][C:35]=2[N:34]=1)([CH3:32])[CH3:31].CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[OH:23][C:20]([CH:17]1[CH2:18][CH2:19][N:14]([C:12]([C:10]2[CH:9]=[CH:8][C:6]3[N:7]=[C:2]([N:34]4[C:35]5[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=5[N:37]=[C:33]4[CH:30]([CH3:32])[CH3:31])[N:3]=[C:4]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[C:5]=3[N:11]=2)=[O:13])[CH2:15][CH2:16]1)([CH3:22])[CH3:21]

Participants

6

Reactant 3

HCID 221212-(propan-2-yl)-1H-1,3-benzodiazoleHCID 23676156Sodium t-butoxideHCID 58404959(2-Chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone

Product 1

HCID 53378372(4-(2-hydroxypropan-2-yl)piperidin-1-yl)(2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methanone

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 178418851HCID 178418851, compoundCatalyst

Procedure

(2-Chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone from Example 118 (80 mg) was reacted with 2-isopropyl-1H-benzo[d]imidazole (1.05 eq), sodium tert-butoxide (2 eq), palladium acetate (0.1 eq) and bis(tri-t-butylphosphine)palladium (0.1 eq). The tube was flushed with nitrogen for 10 minutes before adding Toluene (2 mL). The reaction was microwaved at 145° C. for 20 minutes. The crude was loaded onto a Biotage isolute scx-2 cartridge, eluted with 2M ammonia in MeOH then purified by flash column chromatography to afford 6.6 mg of 119.

Workup

  1. customThe tube was flushed with nitrogen for 10 minutes
  2. additionbefore adding Toluene (2 mL)
  3. customThe reaction was microwaved at 145° C. for 20 minutes
  4. washeluted with 2M ammonia in MeOH
  5. customthen purified by flash column chromatography

Sources & evidence

ORD record
ord-6b0652c4ca194142883e8cdedfbb9f0e
Source dataset
uspto-grants-2013_05
Patent number
US08440651B2

Reaction notes

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