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 1043585Notes

Reaction equation

HRID 1043585 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. MS (Q1) 544.3 (M)+

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-9d15f05f2d924414a1bf08154eed7669
Source dataset
uspto-grants-2013_10
Patent number
US08563540B2

Reaction notes

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