Potassium Carbonate → 5-{[tert-Butyl(dimethyl)silyl]ethynyl}-2-{[6-(morpholin-4-ylmethyl)pyridin-2-yl]amino}thiophene-3-carboxamide

HRID 386140Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([CH2:8][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[CH:4][CH:3]=1.[NH2:15][C:16]1[S:17][C:18]([C:24]#[C:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])=[CH:19][C:20]=1[C:21]([NH2:23])=[O:22].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[K+].[K+]>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]>[Si:26]([C:25]#[C:24][C:18]1[S:17][C:16]([NH:15][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([CH2:8][N:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)[N:7]=2)=[C:20]([C:21]([NH2:23])=[O:22])[CH:19]=1)([C:29]([CH3:31])([CH3:32])[CH3:30])([CH3:28])[CH3:27]

Participants

Conditions

Temperature: 100 °C

Procedure

4-[(6-Bromopyridin-2-yl)methyl]morpholine (Example 45, Step 1) (340 mg, 1.32 mmol), 2-amino-5-{[tert-butyl(dimethyl)silyl]ethynyl}thiophene-3-carboxamide (445 mg, 1.59 mmol), Pd2dba3 (121 mg, 0.13 mmol), X-Phos (315 mg, 0.66 mmol), and K2CO3 (201 mg, 1.46 mmol) were combined in a vial, sealed, and evacuated/backfilled with nitrogen. Degassed t-amyl alcohol (3.3 ml), and the reaction was vigorously stirred at 100° C. overnight. The reaction mixture was then diluted with MeOH, combined with silica, and evaporated. Flash chromatography (dry load, 0-10% MeOH/EtOAc) afforded the title compound as a yellow solid.

Workup

customsealed
customevacuated/backfilled with nitrogen
additionThe reaction mixture was then diluted with MeOH
customevaporated
dry with materialFlash chromatography (dry load, 0-10% MeOH/EtOAc)

Sources & evidence

ORD record: ord-c13545f2cc474191a87ad7a0a154d458
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367706B2

Reaction notes

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