Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[N:11]([Si:15]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[CH:16]([CH3:18])[CH3:17])[C:10]1[CH2:9][CH2:8][CH:7]([N:25]([CH3:27])[CH3:26])[CH2:6][C:5]2=1.C([Li])(C)(C)C.CN(OC)[C:35](=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[OH-].[Na+]>O1CCCC1>[C:35]([C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[N:11]([Si:15]([CH:19]([CH3:20])[CH3:21])([CH:16]([CH3:18])[CH3:17])[CH:22]([CH3:24])[CH3:23])[C:10]1[CH2:9][CH2:8][CH:7]([N:25]([CH3:26])[CH3:27])[CH2:6][C:5]2=1)(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1c2c(c3cc(Br)ccc31)CC(N(C)C)CC2
Reactant: CON(C)C(=O)c1ccccc1
Agent: [Li]C(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)[Si](C(C)C)(C(C)C)n1c2c(c3cc(C(=O)c4ccccc4)ccc31)CC(N(C)C)CC2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 91.1 %

Procedure:
To a solution of 0.50 gm (1.11 mMol) 6-bromo-3-(dimethyl)amino-9-triisopropylsilyl-1,2,3,4-tetrahydro-9H-carbazole in 50 mL tetrahydrofuran at -78° C. were added 1.96 mL (3.33 mMol) t-butyllithium (1.7M in pentane) and the resulting dark solution was allowed to stir for 30 minutes. To this mixture were then added 0.20 gm (1.22 mMol) N-methyl-N-methoxybenzamide and the reaction mixture was allowed to warm to room temperature over 1 hour. The reaction mixture was then treated with 0.1N sodium hydroxide and then extracted well with chloroform. The organic phases were combined, dried over potassium carbonate and concentrated under reduced pressure to give 0.48 gm (91%) of the desired compound as a red-orange oil.
Reaction SMILES: [Li]CCCC.Br[C:7]1[S:11][CH:10]=[N:9][C:8]=1[O:12][CH2:13][CH:14]1[CH2:16][O:15]1.[CH3:17][CH:18]([Si:20](Cl)([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])[CH3:19]>C1COCC1>[CH:18]([Si:20]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[C:10]1[S:11][C:7]2[CH:14]([CH2:16][OH:15])[CH2:13][O:12][C:8]=2[N:9]=1)([CH3:19])[CH3:17]
Reactant: Brc1scnc1OCC1CO1
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)[Si](c1nc2c(s1)C(CO)CO2)(C(C)C)C(C)C
Temperature: -78 °C
Reaction time: 2 h

Procedure:
At −78° C., a soln. of n-BuLi in hexanes (2.18 M, 16.7 mL, 36.4 mmol) was added over 30 min to a soln. of 5-bromo-4-(oxiran-2-ylmethoxy)thiazole (7.17 g, 30.4 mmol) in THF (564 mL). The mixture was stirred at −78° C. for 2 h, then, TIPSCl (6.63 mL, 31.0 mmol) was added, the mixture was allowed to warm to RT and stirred at RT for 30 min. Subsequently, the mixture was cooled to −78° C. and treated with a soln. of n-BuLi in hexanes (2.18 M, 13.9 mL, 30.4 mmol). The mixture was stirred at 0° C. for 2 h, then, it was quenched with aq. sat. NaHCO3 and extracted with EtOAc. The comb. org. layers were washed with brine, dried over MgSO4, and conc. in vacuo. The residue was purified by means of CC (5-50% EtOAc/Hept) to provide a yellow oil.
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][CH3:13])(=[O:11])=[O:10])=[CH:5][C:4]=1[NH:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N+:25]([O-])=O)[CH:23]=2)[N:18]=[CH:17][N:16]=1>CO.[Pd]>[NH2:25][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[N:18]=[CH:17][N:16]=[C:15]2[NH:14][C:4]1[CH:5]=[C:6]([S:9]([NH:12][CH3:13])(=[O:11])=[O:10])[CH:7]=[CH:8][C:3]=1[N:2]([CH3:28])[CH3:1]
Reactant: CNS(=O)(=O)c1ccc(N(C)C)c(Nc2ncnc3ccc([N+](=O)[O-])cc23)c1
Agent: [Pd]
Solvent: CO
Product: CNS(=O)(=O)c1ccc(N(C)C)c(Nc2ncnc3ccc(N)cc23)c1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 65.3 %

Procedure:
A mixture of 4-(dimethylamino)-N-methyl-3-((6-nitroquinazolin-4-yl)amino)benzene-sulfonamide (715 mg, 1.78 mmol) in MeOH (50 mL) was treated with 10% Pd/C (189 mg, 0.178 mmol) and stirred under H2 (balloon) at 25° C. for 2.5 hours before being filtered through celite and concentrated. The residue was dissolved in CH2Cl2/MeOH, washed with saturated aqueous NaHCO3, dried (Na2SO4), and concentrated to give 3-((6-aminoquinazolin-4-yl)amino)-4-(dimethylamino)-N-methylbenzenesulfonamide (433 mg, 59%) as a yellow solid.
Reaction SMILES: [NH:1]([C:13]([O:15]CC1C=CC=CC=1)=O)[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH:23]1[CH:27]=[N:26][N:25]=[N:24]1.[NH:28]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C@H:29](C(O)=O)[CH2:30][NH2:31].CCOC(OC(OCC)=O)=O.CCN(C(C)C)C(C)C>C(O)C.[Pd]>[NH:28]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C@H:29]([C:13]([NH:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)=[O:15])[CH2:30][NH2:31].[NH:23]1[CH:27]=[N:26][N:25]=[N:24]1
Reactant: CC(C)(C)OC(=O)N[C@@H](CN)C(=O)O
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)O)OCc1ccccc1
Agent: [Pd]
Agent: CCOC(=O)OC(=O)OCC
Agent: c1nnn[nH]1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@@H](CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reaction time: 2 h
Yield: 26.7 %

Procedure:
Cbz-Phe-Tetrazole (2.25 g, 6.25 mmole) was then dissolved in ethanol (100 ml) and treated with Pd/C 10% (500 mg, 0.3125 mmole) and stirred under hydrogen for 2 hr. The reaction mixture was filtered through a celite pad and concentrated to dryness. This material was reconstituted in dichloromethane (80 ml) and treated with Boc-Dap (1.88 g, 6.54 mmole), DEPC (1.42 ml, 9.38 mmole) and DIEA (3.8 ml, 21.88 mmole). After 16 hr volatiles were removed to afford crude Boc-Dap-Phe-Tetrazole which was purified by preparative HPLC to give 704 mg (20%) of 1001 as a white powder. Reverse-phase HPLC analysis: 99% at 6.3 min; LCMS (ESI): m/z 458.905 (MH)+, 480.874 (M+Na)+, eluted at 12.95 min.
Reaction SMILES: [CH3:1][C:2]1(C)[C:6](C)(C)OB(C(C)=C)O1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:20]1[C:21]([N:42]2[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:43]2)=[C:22]2[C:28]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])=[CH:27][N:26](C(OC(C)(C)C)=O)[C:23]2=[N:24][CH:25]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:32]1([C:30]([NH:29][C:28]2[C:22]3[C:23](=[N:24][CH:25]=[C:20]([C:2]([CH3:6])=[CH2:1])[C:21]=3[N:42]3[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48][C:49](=[O:50])[O:51][C:52]([CH3:53])([CH3:55])[CH3:54])[CH2:43]3)[NH:26][CH:27]=2)=[O:31])[CH2:34][CH2:33]1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCN(c2c(Br)cnc3c2c(NC(=O)C2CC2)cn3C(=O)OC(C)(C)C)C1
Reactant: C=C(C)B1OC(C)(C)C(C)(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: C=C(C)c1cnc2[nH]cc(NC(=O)C3CC3)c2c1N1CCC[C@@H](NC(=O)OC(C)(C)C)C1
Temperature: 120 °C
Yield: 62.1 %

Procedure:
4,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (436 mg, 2.59 mmol), PS-tetrakis(triphenylphosphine)palladium (786 mg, 0.0864 mmol, 0.10 mmol/1 g) and 2N sodium carbonate (1296 μL, 2.59 mmol) were added to (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (500 mg, 0.864 mmol; Example 107, Step A) in degassed dioxane (1 mL). The reaction was heated to 120° C. for an hour under microwave irradiation. The reaction was then heated to 150° C. for 30 minutes. The reaction was filtered and extracted with DCM. The organic layer was concentrated, and the resulting residue was purified by reverse phase chromatography (Gilson, C-18, 5-95% CH3CN/water) to yield (R)-tert-butyl 1-(3-(cyclopropanecarboxamido)-5-(prop-1-en-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (236 mg, 62% yield).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]([CH3:28])[CH2:13][CH2:14][C:15]1[N:19]([CH2:20][CH2:21][C:22]#[N:23])[C:18]2[CH:24]=[CH:25][CH:26]=[CH:27][C:17]=2[N:16]=1.C(N(CC)CC)C>C(Cl)Cl.O>[O:11]=[C:12]([CH3:28])[CH2:13][CH2:14][C:15]1[N:19]([CH2:20][CH2:21][C:22]#[N:23])[C:18]2[CH:24]=[CH:25][CH:26]=[CH:27][C:17]=2[N:16]=1
Reactant: CC(O)CCc1nc2ccccc2n1CCC#N
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: CC(=O)CCc1nc2ccccc2n1CCC#N
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 105.6 %

Procedure:
To a stirred solution of 1.0 mL of oxalyl chloride in 30 mL of methylene chloride cooled to −78° C. was added 2 mL of anhydrous DMSO. After 10 min, a solution of 2.1 g of 3-[2-(3-hydroxy-butyl)-benzimidazol-1-yl]-propionitrile in 150 mL of dichloromethane was added keeping the temperature below −50° C. After 10 min, 10 mL of triethyl amine was added and the mixture allowed to warm to room temperature. After 15 min, the mixture was diluted with 250 mL of water, shaken and separated. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. Drying under vacuum gave 2.2 g of 3-[2-(3-oxo-butyl)-benzimidazol-1-yl]-propionitrile as an amber resin.
Reaction SMILES: [ClH:1].[NH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][C@@H:4]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1C1ON=C(C)N=1.N[C@H]1CCC[C@@H]1NC(=O)OC(C)(C)C.[N:37]1[N:38](C2C=CC=CC=2C(O)=O)[N:39]=[CH:40][CH:41]=1>>[ClH:1].[NH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][C@@H:4]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:38]1[N:39]=[CH:40][CH:41]=[N:37]1
Reactant: Cc1noc(-c2ccccc2C(=O)N[C@H]2CCC[C@@H]2N)n1
Reactant: O=C(O)c1ccccc1-n1nccn1
Agent: CC(C)(C)OC(=O)N[C@H]1CCC[C@@H]1N
Agent: Cl
Product: N[C@H]1CCC[C@@H]1NC(=O)c1ccccc1-n1nccn1

Procedure:
Prepared according to the procedure for N-[(1S,2S)-2-aminocyclopentyl]-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzamide hydrochloride (Intermediate 2) from tert-butyl N-[(1S,2S)-2-aminocyclopentyl]carbamate (CAS number 586961-34-4; 1.58 g, 7.94 mmol) and 2-(2H-1,2,3-triazol-2-yl)benzoic acid (CAS number 1001401-62-2; 1.64 g, 8.68 mmol) to afford the title compound.
Reaction SMILES: [CH3:1][C@H:2]1[NH:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[CH:10]=[CH:11][C:12]([O:16][CH3:17])=[C:13]([CH:15]=2)[NH2:14])[CH2:3]1.CN1CCOCC1.[Br:25][C:26]1[S:30][C:29]([S:31](Cl)(=[O:33])=[O:32])=[CH:28][CH:27]=1>ClCCl>[Br:25][C:26]1[S:30][C:29]([S:31]([NH:14][C:13]2[CH:15]=[C:9]([N:4]3[CH2:3][C@H:2]([CH3:1])[NH:7][C@H:6]([CH3:8])[CH2:5]3)[CH:10]=[CH:11][C:12]=2[O:16][CH3:17])(=[O:33])=[O:32])=[CH:28][CH:27]=1
Reactant: O=S(=O)(Cl)c1ccc(Br)s1
Reactant: COc1ccc(N2C[C@@H](C)N[C@@H](C)C2)cc1N
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: COc1ccc(N2C[C@@H](C)N[C@@H](C)C2)cc1NS(=O)(=O)c1ccc(Br)s1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)aniline (D4) (1.00 g, 4.25 mmol) in dichloromethane (50 ml) was treated with morpholinomethyl-polystyrene HL resin (2.10 g, 4.0 mmol/g loading, 8.50 mmol) followed by 5-bromo-2-thiophenesulfonyl chloride (1.33 g, 5.09 mmol). The resulting solution was stirred at room temperature overnight and was then filtered and the solvent evaporated. The residue was then chromatographed over silica gel (Flashmaster (II)) eluting with 0 to 10% methanol in dichloromethane 90% for 5 mins, 0-10% 20 mins and 10% 10 mins). The compound was then purified by mass directed autoprep HPLC and the residue further purified by SCX, eluting with methanol first and then NH4OH/methanol. (E122). MS (ES+) m/e 460/462 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH:13]([CH3:17])[CH2:14][O:15][CH3:16])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].I[C:33]1[CH:38]=[CH:37][C:36]([C:39]2[O:40][C:41]([CH3:44])=[N:42][N:43]=2)=[CH:35][CH:34]=1>O1CCOCC1.[Cu](I)I>[CH3:16][O:15][CH2:14][CH:13]([O:12][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([O:1][C:33]2[CH:34]=[CH:35][C:36]([C:39]3[O:40][C:41]([CH3:44])=[N:42][N:43]=3)=[CH:37][CH:38]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])[CH3:17]
Reactant: COCC(C)Oc1cc(O)cc(C(=O)OC)c1
Reactant: Cc1nnc(-c2ccc(I)cc2)o1
Agent: I[Cu]I
Agent: CN(C)CC(=O)O
Agent: Cl
Solvent: C1COCCO1
Product: COCC(C)Oc1cc(Oc2ccc(-c3nnc(C)o3)cc2)cc(C(=O)OC)c1
Temperature: 100 °C
Yield: 67.6 %

Procedure:
To a stirred suspension of Methyl 3-hydroxy-5-(1-methoxypropan-2-yloxy)benzoate (Intermediate 3) (7.88 g, 32.84 mmol, 1.3 equiv.), N,N-dimethylglycine hydrochloride (1 g, 7.69 mmol. 30 mole %), Cesium carbonate (16.5 g, 50.52 mmol, 2 equiv.), copper (II) iodide (0.488 g, 2.56 mmol, 0.1 mole %) in dry dioxane was added 2-(4-iodophenyl)-5-methyl-1,3,4-oxadiazole (7.2 g, 25.26 mmol, 1 equiv.) under nitrogen. The reaction mixture was heated up to reflux at 100° C. for 24 h. The reaction mixture was cooled, quenched with water and extracted with DCM. Combined organic washings were washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo to get the crude product. The crude product was purified by column chromatography using silica gel as stationary phase and EtOAc: petroleum ether as mobile phase to furnish the product (6.8 g) as thick liquid.
Reaction SMILES: CS[C:3]([S:9][CH3:10])=[C:4]([C:7]#[N:8])[C:5]#[N:6].[CH2:11]([O:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1)[CH3:12].C(O)C>C(OCC)C>[C:5]([C:4](=[C:3]([NH:18][C:17]1[CH:19]=[CH:20][C:14]([O:13][CH2:11][CH3:12])=[CH:15][CH:16]=1)[S:9][CH3:10])[C:7]#[N:8])#[N:6]
Reactant: CSC(SC)=C(C#N)C#N
Reactant: CCOc1ccc(N)cc1
Solvent: CCOCC
Solvent: CCO
Product: CCOc1ccc(NC(SC)=C(C#N)C#N)cc1
Temperature: 0 °C

Procedure:
A mixture of 17.03 g (0.1 mol) of 3,3-bis-methylmercapto-2-cyano-acrylonitrile, 12.94 ml (0.1 mol) of 4-ethoxy-aniline and 60 ml of ethanol is heated under reflux for 2 hours. Then, with stirring, 120 ml of diethyl ether are added dropwise to the reaction mixture, which is at approx. 30° C. The reaction mixture is then cooled to 0° C. The title compound precipitates in the form of colorless crystals and is filtered off, washed with diethyl ether and dried under a HV; m.p. 141-142° C.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].[CH3:7][C@:8]12[CH2:25][CH2:24][C@H:23]3[C@@H:13]([CH2:14][CH2:15][C:16]4[C@:21]3([CH3:22])[CH:20]=[CH:19][C:18](=[O:26])[CH:17]=4)[C@@H:12]1[CH2:11][CH2:10][C:9]2=[O:27].C[Si](Cl)(C)C>C(Cl)Cl.CCOCC>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:20]1[C@@:21]2([CH3:22])[C:16]([CH2:15][CH2:14][C@@H:13]3[C@@H:23]2[CH2:24][CH2:25][C@@:8]2([CH3:7])[C@H:12]3[CH2:11][CH2:10][C:9]2=[O:27])=[CH:17][C:18](=[O:26])[CH2:19]1
Reactant: C[C@]12C=CC(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: C=CCCCBr
Agent: C[Si](C)(C)Cl
Solvent: ClCCl
Solvent: CCOCC
Product: C[C@@]12C(=CC(=O)C[C@@H]1CCCCCBr)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reaction time: 0.25 h
Yield: 8 %

Procedure:
Cp2ZrHCl (206 mg, 0.80 mmol, 2.0 eq.) was added to a stirred, room temperature, solution of 5-bromo-1-pentene (0.12 mL, 1.0 mmol, 2.5 eq.) in CH2Cl2 (0.40 mL) under an argon atmosphere. After stirring for about 15 min, the resulting clear yellow solution was transferred via syringe over about 1 min to a clear colourless stirred solution of CuOTf-ligand complex (30.0 mg, 0.040 mmol, 0.10 eq.) in Et2O (2.0 mL) under an argon atmosphere. The resulting dark mixture was allowed to stir for an additional 10 min before 1,4-androstadiene-3,17-dione (114.0 mg, 0.40 mmol, 1.0 eq.) and TMSCl (0.26 mL, 2.00 mmol, 5.0 eq.) were added sequentially dropwise via syringe. Stirring at room temperature was continued arbitrarily for 15 h before the reaction was quenched by the addition of Et2O (ca 3 mL) and NH4Cl (1 M aq., ca 1.5 mL). The mixture was partitioned between the aqueous and Et2O layers and the former phase was extracted with Et2O (3×10 mL). The combined organic phase was washed with NaHCO3 (sat. aq., ca 10 mL), dried (Na2SO4), filtered and concentrated in vacuo to give an oil. Flash column chromatography of the yellow residue (10:30:60 EtOAc/DCM/petrol; SiO2) gave major diastereomer (3) (+)-1α-(5-Bromopentyl)-4-androstene-3,17-dione (107 mg, 0.24 mmol, 60%) and minor diastereomer (3a) (+)-1α-(5-Bromopentyl)-4-androstene-3,17-dione (14 mg, 0.032 mmol, 8%). Diastereomeric ratio (4.8:1) was determined by integration of 1H NMR spectra.
Reaction SMILES: [F:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH2:10]([N:18]=[C:19]=[O:20])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]>CC(N(C)C)=O>[CH2:10]([NH:18][C:19]([N:6]1[CH:7]=[C:2]([F:1])[C:3](=[O:9])[NH:4][C:5]1=[O:8])=[O:20])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: O=c1[nH]cc(F)c(=O)[nH]1
Reactant: CCCCCCCCN=C=O
Solvent: CC(=O)N(C)C
Product: CCCCCCCCNC(=O)n1cc(F)c(=O)[nH]c1=O
Reaction time: 8 h
Yield: 43.2 %

Procedure:
40 ml of dimethyl acetamide was added to 10.01 g of 5-fluorouracil and 11.95g of n-octyl isocyanate. After the reaction was carried out at 60° C for an hour, the reaction mixture was allowed to stand overnight at room temperature. The solvent was distilled off and to the residue were added 200 ml of chloroform and 300 ml of water to effect extraction. The chloroform layer was dried over anhydrous sodium sulfate. After evaporating off the chloroform, the precipitated crystals were recrystallized from ethanol to obtain 9.49 g of 1-(N-n-octylcarbamoyl)-5-fluorouracil melting at 98°-100° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([F:20])=[C:16]([OH:19])[N:17]=2)[C:12](=[O:21])[C:11]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:10]1.C(N(CC)CC)C.[N+:34]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[S:43](Cl)(=[O:45])=[O:44])([O-:36])=[O:35].C(OCC)(=O)C>C(Cl)Cl.C(OCC)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([F:20])=[C:16]([O:19][S:43]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=3[N+:34]([O-:36])=[O:35])(=[O:44])=[O:45])[N:17]=2)[C:12](=[O:21])[C:11]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:10]1
Reactant: CCOC(=O)c1cn(-c2ccc(F)cc2F)c2nc(O)c(F)cc2c1=O
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)c1cn(-c2ccc(F)cc2F)c2nc(OS(=O)(=O)c3ccccc3[N+](=O)[O-])c(F)cc2c1=O
Reaction time: 6 h
Yield: 97.2 %

Procedure:
In 30 ml of methylene chloride was suspended 3.00 g of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-7-hydroxy-4-oxo-1,8-naphthyridine-3-carboxylate, and 1.02 g of triethylamine and 2.20 g of ortho-nitrobenzenesulfonyl chloride were added thereto with ice-cooling, after which the resulting mixture was subjected to reaction at the same temperature for 30 minutes and then at room temperature for 6 hours. The reaction mixture was washed with three 50-ml portions of water and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the residue thus obtained was added a mixture of 6 ml of ethyl acetate and 12 ml of diethyl ether, after which the crystals thus despotied were collected by filtration to obtain 4.40 g (yield 97.2%) of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-7-(2-nitrobenzenesulfonyloxy)-4-oxo-1,8-naphthyridine-3-carboxylate having a melting point of 157°-160° C.
Reaction SMILES: FC(F)(F)C(O)=O.[F:8][C:9]1[CH:38]=[CH:37][C:12]([NH:13][C:14]2[CH:26]=[C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[O:33][CH:34]([CH3:36])[CH3:35])[CH:24]=[CH:23][C:15]=2[C:16]([O:18]C(C)(C)C)=[O:17])=[CH:11][CH:10]=1>>[F:8][C:9]1[CH:38]=[CH:37][C:12]([NH:13][C:14]2[CH:26]=[C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[O:33][CH:34]([CH3:35])[CH3:36])[CH:24]=[CH:23][C:15]=2[C:16]([OH:18])=[O:17])=[CH:11][CH:10]=1
Reactant: CC(C)Oc1ccccc1-c1ccc(C(=O)OC(C)(C)C)c(Nc2ccc(F)cc2)c1
Solvent: O=C(O)C(F)(F)F
Product: CC(C)Oc1ccccc1-c1ccc(C(=O)O)c(Nc2ccc(F)cc2)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Trifluoroacetic acid 5.0 mL was added to the obtained tert-butyl 2-(4-fluoroanilino)-4-(2-isopropoxyphenyl)benzoate, and it was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure, and the obtained residue was refined by reversed-phase silica gel column chromatography [eluent; 80-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to give 2-(4-fluoroanilino)-4-(2-isopropoxyphenyl)benzoic acid 16 mg of a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[C:9]2[C:17]3[C:12](=[C:13]([CH2:18][S:19][CH3:20])[CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[C:4]([CH3:28])[CH:3]=1.ClCCl.ClC1C=CC=C(C(OO)=[O:40])C=1>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[C:9]2[C:17]3[C:12](=[C:13]([CH2:18][S:19]([CH3:20])=[O:40])[CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[C:4]([CH3:28])[CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCc1cccc2c(C(c3ccc(F)cc3)c3ccc(Cl)cc3C)c[nH]c12
Solvent: CO
Solvent: ClCCl
Product: Cc1cc(Cl)ccc1C(c1ccc(F)cc1)c1c[nH]c2c(CS(C)=O)cccc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
130 mg (0.32 mmol) of the compound from Example 102 were introduced into 15 ml of dichloromethane at 0° C., 78 mg (0.32 mmol) of 70% pure meta-chloroperbenzoic acid were added, and the mixture was stirred at RT for 2 h. 2 ml of methanol were added, and the solution was concentrated. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water gradient). 129 mg (96% of theory) of the title compound were obtained as mixture of diastereomers.
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]([OH:16])([CH3:15])[CH3:14].[B:17](OC)(OC)[O:18]C>C1COCC1>[CH3:14][C:13]1([CH3:15])[O:16][B:17]([OH:18])[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]1=2
Reactant: COB(OC)OC
Reactant: CC(C)(O)c1ccccc1Br
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC1(C)OB(O)c2ccccc21
Temperature: -75 °C
Reaction time: 0.5 h
Yield: 40 %

Procedure:
To a solution of n-BuLi (21.2 ml, 0.053 mol) in anhydrous THF (160 mL) at −78° C. under argon was slowly added a solution of 2-(2-bromophenyl)propan-2-ol (XCV) (0.0212 mol, 4.55 g) in anhydrous THF (50 mL) while maintaining the temperature below −65° C. After addition was complete, the reaction mixture was stirred at −75° C. for 30 min. To this mixture was added in portions trimethyl borate (0.032 mol, 3.3 g), and the reaction mixture was stirred at −78° C. for 30 min and then at room temperature overnight. The mixture was cooled to 0° C., carefully quenched with 1M aqueous HCl, and stirred at room temperature for 15 min. The mixture was acidified to pH 3 with 2M HCl and stirring was continued for 1 hour. The two phases were separated and the aqueous layer was extracted with EtOAc. The combined organic phases were dried over MgSO4. The crude product was purified by silica gel chromatography using DCM followed by DCM/MeOH 300/1 to give 3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol (XCVI) as a light yellow oil (1.37 g; 8.5 mmol, 40% yield). 1H NMR (CDCl3) δ ppm 1.54 (s, 6H), 7.25-7.29 (m, 1H), 7.33 (d, J=7 Hz, 1H), 7.45 (td, J=7 Hz, J=1 Hz, 1H), 7.68 (d, J=7 Hz, 1H).