N-methylthiophen-3-amine → HCID 68108621, compound

HRID 1809722

Reaction equation

HRID 1809722 reaction equation
Br[C:2]1[CH:3]=[C:4]([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:6][CH:7]=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>O1CCOCC1.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]>[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:4]4[CH:5]=[CH:6][CH:7]=[C:2]([NH:42][CH2:41][C:36]5[CH:37]=[CH:38][S:34][CH:35]=5)[CH:3]=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 68109320HCID 68109320, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 68108621HCID 68108621, compound

Reagents, catalysts & solvents 2

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

Procedure

To a stirred solution of [3-(3-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine (from Example 40 supra) (250 mg, 0.47 mmol), thiophen-3-yl-methylamine (54 mg, 0.564 mmol), DavePhos (37 mg, 20% mol) and t-BuONa (54 mg, 0.564 mmol) in 1,4-dioxane (10 mL), Pd2(dba)3 (27 mg, 10% mol) was added in one portion under N2 atmosphere. The resultant mixture was stirred at 100° C. for 6 hours. The mixture was cooled and filtered; the filtrate was evaporated under reduced pressure to give the crude product. It was purified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH, 100:1, v/v) to give (2-morpholin-4-yl-ethyl)-[3-{3-[(thiophen-3-ylmethyl)-amino]-phenyl}-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-amine. (Yield 150 mg, 56%).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. customthe filtrate was evaporated under reduced pressure
  4. customto give the crude product
  5. customIt was purified by chromatography (silica gel, 200-300 mesh, dichloromethane

Sources & evidence

ORD record
ord-6df41e9b6d7f4933b3a1389869b6991f
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Linked notes

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