N-methylthiophen-3-amine → HCID 68108327, compound

HRID 1809737

Reaction equation

HRID 1809737 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][C:13]([NH:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[N:14][CH:15]=3)[N:10]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[S:34]1[CH:38]=[CH:37][C:36](NC)=[CH:35]1.[CH3:41][N:42](C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C(O[Na])(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[N:20]1([CH2:19][CH2:18][NH:17][C:13]2[N:12]=[C:11]3[N:10]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:9]=[C:8]([C:6]4[CH:5]=[CH:4][CH:3]=[C:2]([NH:42][CH2:41][C:36]5[CH:37]=[CH:38][S:34][CH:35]=5)[N:7]=4)[C:16]3=[CH:15][N:14]=2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 642344N-methylthiophen-3-amineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86667960[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amineHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 68108327HCID 68108327, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A sealed tube was charged with [3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine (from Example 32 supra) (320 mg, 0.60 mmol), thiophen-3-yl-methylamine (81 mg, 0.72 mmol), Pd2(dba)3 (34 mg), DavePhos (47 mg), t-BuONa (69 mg, 0.72 mmol) and dioxane (12 mL). The mixture was stirred at 105° C. under an atmosphere of N2 for 8 hours. After cooling to room temperature, the mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 16 g, 100-200 mesh, eluting with MeOH:dichloromethane, 1:100 to 1:80) to give crude (2-morpholin-4-yl-ethyl)-[3-{6-[(thiophen-3-ylmethyl)-amino]-pyridin-2-yl}-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-amine as a yellow oil. (Yield 149 mg).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (silica gel, 16 g, 100-200 mesh, eluting with MeOH:dichloromethane, 1:100 to 1:80)

Sources & evidence

ORD record
ord-4a051e2fb0b14a8393547a84528e151e
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Linked notes

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