2-Amino-5-bromo-N,N-dimethylbenzamide → 2,2-Dimethyl-propionic acid 5-(4-amino-3-dimethylcarbamoyl-phenyl)-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

HRID 1865700Notes

Reaction equation

HRID 1865700 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](C3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[N:10]=1.[NH2:35][C:36]1[CH:46]=[CH:45][C:44](Br)=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39]>C1COCC1.C(#N)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[NH2:35][C:36]1[CH:46]=[CH:45][C:44]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:10][N:11]([CH2:27][O:28][C:29](=[O:34])[C:30]([CH3:31])([CH3:33])[CH3:32])[C:12]3=[N:13][CH:14]=2)=[CH:43][C:37]=1[C:38](=[O:39])[N:40]([CH3:41])[CH3:42]

Participants

5

Reactant 2

HCID 509995122-Amino-5-bromo-N,N-dimethylbenzamideHCID 579757482,2-Dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3]dioxolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

Product 1

HCID 579758402,2-Dimethyl-propionic acid 5-(4-amino-3-dimethylcarbamoyl-phenyl)-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl esterYield 52.7%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 22177404Acetonitrile tetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,2-dimethyl-propionic acid 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3]dioxolan-2-yl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (6.5 g, 14 mmol), 2-amino-5-bromo-N,N-dimethyl-benzamide (3.4 g, 14 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]-palladium(II) dichloromethane adduct (511 mg, 0.7 mmol) in THF/Acetonitrile/saturated NaHCO3 (25 ml/25 ml/30 ml) was stirred at 100° C. for 4 hours. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 2,2-dimethyl-propionic acid 5-(4-amino-3-dimethylcarbamoyl-phenyl)-3-(2-methoxy-phenyl)-pyrazolo[3,4-b]pyridin-1-ylmethyl ester (3.7 g, 52% yield).

Workup

  1. temperatureto cool down to room temperature
  2. extractionextracted with ethyl acetate (3×)
  3. extractionThe combined organic layers were extracted with brine
  4. dry with materialdried with Na2SO4
  5. customdecanted
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-3ce60f191be5467e8bb4d5a9dedab8ff
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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