Sodium Bicarbonate → 2-(6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole

HRID 520608

Reaction equation

HRID 520608 reaction equation
C(=O)(O)[O-].[Na+].Cl[C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[N:12][N:13]2[S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:18])=[O:17])=[C:9]([C:25]2[O:26][C:27]([CH2:30][N:31]3[CH2:36][CH2:35][N:34]([CH:37]([CH3:39])[CH3:38])[CH2:33][CH2:32]3)=[CH:28][N:29]=2)[CH:8]=1.CC1(C)C(C)(C)OB([C:48]2[CH:56]=[CH:55][CH:54]=[C:53]3[C:49]=2[CH:50]=[CH:51][NH:52]3)O1>O.C(O)(C)C>[NH:52]1[C:53]2[C:49](=[C:48]([C:7]3[CH:15]=[C:14]4[C:10]([CH:11]=[N:12][N:13]4[S:16]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)(=[O:17])=[O:18])=[C:9]([C:25]4[O:26][C:27]([CH2:30][N:31]5[CH2:36][CH2:35][N:34]([CH:37]([CH3:38])[CH3:39])[CH2:33][CH2:32]5)=[CH:28][N:29]=4)[CH:8]=3)[CH:56]=[CH:55][CH:54]=2)[CH:50]=[CH:51]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 595647082-[1-(Benzenesulfonyl)-6-chloroindazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

Product 1

HCID 666957552-(6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazoleYield 96.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

A solution of sodium bicarbonate (228.0 g) in water (2.7 L) was added to a suspension of 6-Chloro-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (271.2 g) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (263.2 g, available from Apollo Scientific Limited) in isopropanol (2.7 L) stirred under nitrogen at ambient temperature. After degassing, via evacuation and flushing with nitrogen, 2′-(dimethylamino)-2-biphenylyl-palladium(II) chloride dinorbornylphosphine complex (29.83 g) was added. The mixture was degassed again and was then heated to 90±3° C. and held at this temperature for 2 hours. The mixture was cooled to 20±5° C. over 25 minutes and aged at this temperature overnight. The resultant suspension was filtered, washed with water (1.35 L) and then slurried with toluene (4×1.35 L). The solid was dried under vacuum at 50° C. to give the title compound as grey solid (302.7 g).

Workup

  1. customAfter degassing, via evacuation
  2. customflushing with nitrogen, 2′-(dimethylamino)-2-biphenylyl-palladium(II) chloride dinorbornylphosphine complex (29.83 g)
  3. additionwas added
  4. customThe mixture was degassed again
  5. temperaturewas then heated to 90±3° C.
  6. temperatureThe mixture was cooled to 20±5° C. over 25 minutes
  7. customaged at this temperature overnight
  8. filtrationThe resultant suspension was filtered
  9. washwashed with water (1.35 L)
  10. customThe solid was dried under vacuum at 50° C.

Sources & evidence

ORD record
ord-9d34cb598a6f4d57ae4a7587a97c519a
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Linked notes

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