Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][CH2:11][CH2:12][N:13]([CH2:21][C@H:22]([O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[C:23]2[CH:32]=[CH:31][C:30]([OH:33])=[C:29]3[C:24]=2[CH:25]=[CH:26][C:27](=[O:34])[NH:28]3)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:4][CH:3]=1.[CH2:43]([N:45]1[C:49]2=[N:50][C:51]([CH2:72][CH3:73])=[C:52]([CH2:61][NH:62][C:63]3[C:64](=O)[C:65](=[O:70])[C:66]=3[O:67]CC)[C:53]([NH:54][CH:55]3[CH2:60][CH2:59][O:58][CH2:57][CH2:56]3)=[C:48]2[CH:47]=[N:46]1)[CH3:44]>C(O)C>[Si:36]([O:35][C@H:22]([C:23]1[CH:32]=[CH:31][C:30]([OH:33])=[C:29]2[C:24]=1[CH:25]=[CH:26][C:27](=[O:34])[NH:28]2)[CH2:21][N:13]([CH2:12][CH2:11][CH2:10][C:9]#[C:8][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:64]2[C:65](=[O:70])[C:66](=[O:67])[C:63]=2[NH:62][CH2:61][C:52]2[C:53]([NH:54][CH:55]3[CH2:60][CH2:59][O:58][CH2:57][CH2:56]3)=[C:48]3[CH:47]=[N:46][N:45]([CH2:43][CH3:44])[C:49]3=[N:50][C:51]=2[CH2:72][CH3:73])=[CH:7][CH:6]=1)[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:37])[CH3:38]
Reactant: CCOc1c(NCc2c(CC)nc3c(cnn3CC)c2NC2CCOCC2)c(=O)c1=O
Reactant: CC(C)(C)OC(=O)N(CCCC#Cc1ccc(N)cc1)C[C@H](O[Si](C)(C)C(C)(C)C)c1ccc(O)c2[nH]c(=O)ccc12
Solvent: CCO
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNc1c(Nc2ccc(C#CCCCN(C[C@H](O[Si](C)(C)C(C)(C)C)c3ccc(O)c4[nH]c(=O)ccc34)C(=O)OC(C)(C)C)cc2)c(=O)c1=O
Temperature: 70 °C

Procedure:
A mixture of Intermediate 38 (0.11 g, 0.19 mmol) and Intermediate 28 (0.15 g, 0.36 mmol) in ethanol (2 mL) was heated for 3 days in a 70° C. oil bath. The mixture was concentrated under reduced pressure and was then purified by automated flash silica gel chromatography, using a 12 g Silicycle SiliSep flash column (dichloromethane/methanol) to give the impure intermediate, (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl(5-(4-(2-((1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methylamino)-3,4-dioxocyclobut-1-enylamino)phenyl)pent-4-ynyl)carbamate. This material was then subjected to reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1 TFA) to provide, after concentration, the intermediate (R)-tert-butyl 5-(4-(2-((1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methylamino)-3,4-dioxocyclobut-1-enylamino)phenyl)pent-4-ynyl(2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)carbamate. This intermediate was dissolved in methanol (5 mL) and treated with palladium on carbon (10% w/w, wet Degussa-type, catalytic amount). The suspension was stirred under a balloon of hydrogen gas until LC/MS analysis indicated the complete reduction of the triple bond. The mixture was then filtered through a pad of Celite diatomaceous earth, and the filtrate was concentrated to dryness under reduced pressure. The residue was taken up in dichloromethane/methanol (1:1, 5 mL) and treated with a solution of hydrogen chloride in dioxane (4 N, 2 mL). Once LC/MS analysis showed the complete removal of the Boc-protecting group, the mixture was concentrated to dryness. The residue was purified by reverse-phase high performance liquid chromatography (RP-HPLC, acetonitrile/water/0.1% TFA) to provide, after concentration, the trifluoroacetic acid salt of the title compound as a pale yellow powder (28 mg).