Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[CH2:3][C:4](O)=[O:5].F[P-](F)(F)(F)(F)F.CN(C(=[N+](C)C)ON1C2=NC=CC=C2N=N1)C.C(N(C(C)C)CC)(C)C.[NH:42]1[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48][C:49]2[CH:54]=[CH:53][N:52]=[C:51]([C:55]3[CH:56]=[N:57][N:58]4[CH:63]=[CH:62][C:61]([C:64]#[N:65])=[CH:60][C:59]=34)[N:50]=2)[CH2:43]1>CN(C=O)C>[F:1][C:2]([F:8])([F:7])[CH2:3][C:4]([N:42]1[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48][C:49]2[CH:54]=[CH:53][N:52]=[C:51]([C:55]3[CH:56]=[N:57][N:58]4[CH:63]=[CH:62][C:61]([C:64]#[N:65])=[CH:60][C:59]=34)[N:50]=2)[CH2:43]1)=[O:5]
Reactant: O=C(O)CC(F)(F)F
Reactant: N#Cc1ccn2ncc(-c3nccc(N[C@@H]4CCCNC4)n3)c2c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: N#Cc1ccn2ncc(-c3nccc(N[C@@H]4CCCN(C(=O)CC(F)(F)F)C4)n3)c2c1
Temperature: 25 °C
Reaction time: 20 h
Yield: 19.4 %

Procedure:
3,3,3-Trifluoropropanoic acid (0.03 mL, 0.29 mmol), N-[(dimethylamino)(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methylmethanaminium hexafluorophosphate (0.12 g, 0.30 mmol) and diisopropylethylamine (0.21 mL, 1.21 mmol) were added to a stirred solution of 3-{4-[(3R)-piperidin-3-ylamino]pyrimidin-2-yl}pyrazolo[1,5-a]pyridine-5-carbonitrile (Preparation 7b, 0.11 g, 0.24 mmol) in N,N′-dimethylformamide (3 mL) and the mixture was stirred at room temperature for 20 hours. The reaction mixture was then partitioned between dichloromethane and 4% aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with 4% aqueous sodium hydrogen carbonate solution, dried (MgSO4) and the solvents were evaporated in vacuo. The crude product was purified by flash chromatography (200:1 to 10:1 chloroform/methanol) to give a residue that was repurified by flash chromatography (1:1 hexane/ethyl acetate to 100% ethyl acetate) to give the title compound (0.02 g, 19%) as a pale yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:10][N:11]([CH3:24])[CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=1>>[Br:1][C:2]1[CH:3]=[C:4]2[N:9]=[C:20]([C:19]3[CH:22]=[CH:23][C:16]([O:15][CH2:14][CH2:13][CH2:12][N:11]([CH3:24])[CH3:10])=[CH:17][CH:18]=3)[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CN(C)CCCOc1ccc(C=O)cc1
Reactant: Nc1cc(Br)cnc1N
Product: CN(C)CCCOc1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1

Procedure:
The title compound was prepared from 5-bromo-2,3-diaminopyridine (376 mg, 2 mmol) and 4-[3-(dimethylamino)-propoxy]benzaldehyde (420 mg, 2 mmol).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[C:13](Cl)=[O:14])=[CH:4][CH:3]=1.[CH3:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18]1>ClCCl>[CH3:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]1[C:13]([C:9]1[CH:10]=[N:11][O:12][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)=[O:14]
Reactant: Cc1ccc(-c2oncc2C(=O)Cl)cc1
Reactant: CC1Cc2ccccc2N1
Solvent: ClCCl
Product: Cc1ccc(-c2oncc2C(=O)N2c3ccccc3CC2C)cc1
Reaction time: 1 h

Procedure:
To 5-(4-methylphenyl)isoxazole-4-carbonyl chloride (10 mg, 0.045 mmol) in dichloromethane (1 mL) was added 2-methylindoline (6.6 mg, 0.050 mmol, 1.1 eq.), and the reaction mixture was stirred for 1 h. The solvent was removed, and the residue was purified by preparative reverse-phase HPLC to give the title compound. HRMS (ESI, pos. ion) m/z calcd for C20H18N2O2: 318.1368, found 318.1379.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([F:10])[F:9].[Li]CCCC.C(O[B:20]1[O:24][C:23]([CH3:26])([CH3:25])[C:22]([CH3:28])([CH3:27])[O:21]1)(C)C.O>C1COCC1.C(OCC)(=O)C>[F:9][CH:8]([F:10])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[B:20]1[O:24][C:23]([CH3:26])([CH3:25])[C:22]([CH3:28])([CH3:27])[O:21]1
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Reactant: FC(F)c1ccccc1Br
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CC1(C)OB(c2ccccc2C(F)F)OC1(C)C
Temperature: -78 °C
Yield: 59.2 %

Procedure:
To a solution of 1-bromo-2-difluoromethyl-benzene (19.8 g, 95.7 mmol) in dry THF (200 ml) at −78° C. under a nitrogen atmosphere was added 2.5 M n-BuLi in hexanes (42 ml, 105 mmol) slowly. After completion of the addition, the resulting dark solution was stirred for an additional hour at −78° C. Subsequently, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (25 ml, 123 mmol) was added, and the solution was slowly warmed to room temperature. After stirring overnight at room temperature under a nitrogen atmosphere the solution was poured into 400 ml water. Ethyl acetate (300 ml) was added and the layers were separated. The aqueous layer was extracted twice with ethyl acetate (150 ml and 50 ml respectively), and the combined organic layers were washed with water, dried over Na2SO4, filtered, and evaporated to dryness under reduced pressure. The resulting brown oil (21 g) was purified by bulb-to-bulb-distillation at 3×10−3 mbar at 90-95° C. to yield 2-(2-difluoromethyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (14.4 g, 59%) as a slightly yellow oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[NH:7][C@@H:8]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:27])[NH:17][C:18]1[N:19]=[C:20]2[N:24]([CH:25]=1)[CH:23]=[C:22](Br)[S:21]2)=[O:10])([CH3:4])([CH3:3])[CH3:2].[CH3:35][O:36][C:37](=[O:70])[NH:38][C@H:39]([C:43]([N:45]1[CH2:49][CH2:48][CH2:47][C@H:46]1[C:50]1[NH:51][C:52]([C:55]2[CH:60]=[CH:59][C:58](B3OC(C)(C)C(C)(C)O3)=[CH:57][CH:56]=2)=[CH:53][N:54]=1)=[O:44])[CH:40]([CH3:42])[CH3:41]>>[CH3:35][O:36][C:37](=[O:70])[NH:38][C@H:39]([C:43]([N:45]1[CH2:49][CH2:48][CH2:47][C@H:46]1[C:50]1[NH:51][C:52]([C:55]2[CH:56]=[CH:57][C:58]([C:22]3[S:21][C:20]4=[N:19][C:18]([NH:17][C:16]([C@@H:12]5[CH2:13][CH2:14][CH2:15][N:11]5[C:9](=[O:10])[C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:34])[C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)=[O:27])=[CH:25][N:24]4[CH:23]=3)=[CH:59][CH:60]=2)=[CH:53][N:54]=1)=[O:44])[CH:40]([CH3:42])[CH3:41]
Reactant: COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)[nH]1)C(C)C
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)Nc1cn2cc(Br)sc2n1)c1ccccc1
Product: COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(-c3cn4cc(NC(=O)[C@@H]5CCCN5C(=O)[C@@H](NC(=O)OC(C)(C)C)c5ccccc5)nc4s3)cc2)[nH]1)C(C)C
Yield: 10 %

Procedure:
Compound A38 was synthesized from compound 23 (0.091 mmol) and compound 8 (0.137 mmol), following the procedure as described for compound A1 (reaction time=1 hr), as a white lyophilized powder in 10% yield. MS (ESI, EI+) m/z=838.39 (MH+).
Reaction SMILES: C([N:5]1[C:10](=[O:11])[C:9]([NH:12][CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[CH2:17][CH2:16]2)=[C:8]([Cl:31])[CH:7]=[N:6]1)(C)(C)C>Cl>[Cl:31][C:8]1[CH:7]=[N:6][NH:5][C:10](=[O:11])[C:9]=1[NH:12][CH2:13][CH2:14][N:15]1[CH2:16][CH2:17][N:18]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=2)[CH2:19][CH2:20]1
Reactant: CC(C)(C)n1ncc(Cl)c(NCCN2CCN(c3cccc(C(F)(F)F)c3)CC2)c1=O
Agent: Cl
Product: O=c1[nH]ncc(Cl)c1NCCN1CCN(c2cccc(C(F)(F)F)c2)CC1

Procedure:
4.25 g (0.0093 mol) of 2-t-butyl-5-chloro-4-((2(4-(3-trifluoromethylphenyl)-1-piperazinyl)ethyl)amino)-3(2H)-pyridazinone are stirred with 50 ml of concentrated aqueous hydrochloric acid at room temperature for 72 hours, made basic and extracted 3 times with chloroform, 10 the organic phase is concentrated and dried with sodium sulphate, and the residue is triturated with acetone. The crystalline precipitate of 5-chloro-4-((2-(4-(3-trifluoromethylphenyl)-1-piperazinyl)ethyl)amino)-3(2H)-pyridazinone weighs 2.40 g (47.7% of theory). It is converted by dissolving in 100 ml of hot absolute ethanol and adding ethereal hydrochloric acid into 2.20 g (46.7% of theory) of dihydrochloride of m.p. 220°-223° C.; C 40.6%, H 4.2%, Cl(tot) 21.1%, Cl- 14.2%, F 11.5%, N 13.9%, O 8.7%, UV in 0.1N HCl: 208(4.42), 226(S,4.22), 300(4.47).
Reaction SMILES: [NH2:1][C@H:2]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[C:10]([OH:12])=[O:11].[CH:13]1C=CC=CC=1.C[Si](C=[N+]=[N-])(C)C>CO.C(OCC)C>[CH3:13][O:11][C:10]([C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C@@H:2]1[NH2:1])=[O:12]
Reactant: c1ccccc1
Reactant: N[C@H]1CCCCCC[C@H]1C(=O)O
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: CCOCC
Solvent: CO
Product: COC(=O)[C@@H]1CCCCCC[C@@H]1N
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 94 %

Procedure:
cis-2-Amino-cyclooctanecarboxylic acid (0.65 g, 3.8 mmol) was dissolved in methanol (5 mL). Benzene (7.5 mL) was added followed by dropwise addition of a 2.0 M solution of (trimethylsilyl)diazomethane in diethyl ether (3.5 mL). The yellow solution was stirred at 25° C. for 45 min. The solution was concentrated in vacuo. The residue was dissolved in methanol (20 mL) and concentrated in vacuo to afford the desired product, cis-2-amino-cyclooctanecarboxylic acid methyl ester (0.66 g, 3.56 mmol, 94%), as a colorless oil. LC-MS (ESI) calcd for C10H19NO2 185.14, found 186.2 [M+H+].
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[O:6][C@H:5]2[CH2:7][S:8][C@H:9]([C@H:10]([OH:13])CO)[C@H:4]2[O:3]1>C(OCC)(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4]>[CH3:1][C:2]1([CH3:14])[O:6][C@H:5]2[CH2:7][S:8][C@H:9]([CH:10]=[O:13])[C@H:4]2[O:3]1
Reactant: CC1(C)O[C@@H]2[C@@H]([C@H](O)CO)SC[C@@H]2O1
Agent: CC(=O)[O-]
Agent: [Pb+4]
Solvent: CCOC(C)=O
Product: CC1(C)O[C@H]2[C@H](CS[C@@H]2C=O)O1
Reaction time: 0.17 h
Yield: 99.6 %

Procedure:
2.5 g (11.2 mmol) of (1R)-1-((3aS,4R,6aR)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)-ethane-1,2-diol from the aforementioned Experimental Example 5 were dissolved in ethyl acetate to which lead tetraacetate were added at 0° C., and the reaction mixture was stirred for 10 min. The reaction mixture was filtered. Ethyl acetate was added to the filtrate, which was washed with saturated sodium bicarbonate, dried, and filtered. The filtrate was concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography using the eluant (hexane:ethyl acetate=5:1) to obtain 2.1 g (yield: 98%) of (3aS,4S,6aR)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxole-4–Carbaldehyde as an oil.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([O:10][CH3:11])[N:3]=1.[C:12]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[S:24]([N:27]=[C:28]=[S:29])(=[O:26])=[O:25])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1(C)C=CC=CC=1>[C:18]1([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[S:24]([NH:27][C:28]([NH:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([O:10][CH3:11])[N:3]=1)=[S:29])(=[O:25])=[O:26]
Reactant: COc1nc(N)nc(OC)n1
Reactant: O=S(=O)(N=C=S)c1ccccc1-c1ccccc1
Solvent: Cc1ccccc1
Product: COc1nc(NC(=S)NS(=O)(=O)c2ccccc2-c2ccccc2)nc(OC)n1
Yield: 81.2 %

Procedure:
15.6 g of 2-amino-4,6-dimethoxy-1,3,5-triazine were suspended in 300 ml of dry toluene, and 27.5 g of 2-phenylbenzenesulfonyl isothiocyanate were added. The mixture was heated under reflux for 8 hours. After cooling, the resulting precipitate was collected by filtration and recrystallized from ethanol to give 35 g of 1-(2-biphenylylsulfonyl) 3-(4,6-dimethoxy-1,3,5-triazin-2-yl)thiourea represented by the following formula: ##STR28##
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:7]=[C:8]([NH2:12])[CH:9]=[CH:10][CH:11]=1.F[C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]=1[N+:23]([O-:25])=[O:24]>CN1C(=O)CCC1.O>[N+:23]([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:14]=1[NH:12][C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[CH:7]=1)[C:18]([OH:20])=[O:19])([O-:25])=[O:24]
Reactant: O=C(O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: Nc1cccc(-c2nccs2)c1
Solvent: O
Solvent: CN1CCCC1=O
Product: O=C(O)c1ccc(Nc2cccc(-c3nccs3)c2)c([N+](=O)[O-])c1
Yield: 83.4 %

Procedure:
To a solution of 3-thiazol-2-yl-phenylamine (14.0 g, 79 mmol) in anhydrous NMP (50 ml) was added 4-fluoro-3-nitrobenzoic acid (15.0 g, 127 mmol). The resultant mixture was stirred at 90° C. over night. The cooled reaction cake was suspended in water and the solid was filtered off, washed with water and dried in the air to afford the desired product (22.5 g, 83%).
Reaction SMILES: Cl.Cl.[O:3]1[CH2:8][CH2:7][CH:6]([N:9]2[CH2:14][CH2:13][CH:12]([NH2:15])[CH2:11][CH2:10]2)[CH2:5][CH2:4]1.O.C(N(CC)CC)C.Cl[C:25]1[CH:30]=[CH:29][C:28]([S:31]([NH2:34])(=[O:33])=[O:32])=[CH:27][C:26]=1[N+:35]([O-:37])=[O:36]>O1CCOCC1>[N+:35]([C:26]1[CH:27]=[C:28]([S:31]([NH2:34])(=[O:32])=[O:33])[CH:29]=[CH:30][C:25]=1[NH:15][CH:12]1[CH2:13][CH2:14][N:9]([CH:6]2[CH2:5][CH2:4][O:3][CH2:8][CH2:7]2)[CH2:10][CH2:11]1)([O-:37])=[O:36]
Reactant: NC1CCN(C2CCOCC2)CC1
Reactant: NS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Solvent: CCN(CC)CC
Product: NS(=O)(=O)c1ccc(NC2CCN(C3CCOCC3)CC2)c([N+](=O)[O-])c1
Temperature: 90 °C

Procedure:
A mixture of EXAMPLE 49B (22.12 g), water (43 mL), and triethylamine (43.6 mL) in 1,4-dioxane (300 mL) was stirred at room temperature until EXAMPLE 49B completely dissolved. The solution was then treated with 4-chloro-3-nitrobenzenesulfonamide (20.3 g), heated at 90° C. for 16 hours, cooled and concentrated. 10% Methanol in dichloromethane was added, and the solution was stirred vigorously at room temperature until a fine suspension existed and then the mixture was filtered.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)=[CH:19][CH:18]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(OC(=O)[O:34][C:35]1[CH:40]=[CH:39][C:38]([S:41](Cl)(=[O:43])=[O:42])=[CH:37][CH:36]=1)C.C(N(CC)CC)C.O>C(Cl)Cl>[OH:34][C:35]1[CH:40]=[CH:39][C:38]([S:41]([N:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:14][CH:13]=2)[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)=[CH:19][CH:18]=2)(=[O:43])=[O:42])=[CH:37][CH:36]=1
Reactant: CCOC(=O)Oc1ccc(S(=O)(=O)Cl)cc1
Reactant: c1cc(OC2CCCCO2)ccc1CNc1ccc(OCCN2CCCC2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: O=S(=O)(c1ccc(O)cc1)N(Cc1ccc(OC2CCCCO2)cc1)c1ccc(OCCN2CCCC2)cc1
Reaction time: 60 h

Procedure:
A solution of [4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-[4-(tetrahydro-pyran-2-yloxy)-benzyl]-amine (264 mg, 0.666 mmol) in methylene chloride (10 mL) was treated with carbonic acid 4-chlorosulfonyl-phenyl ester ethyl ester (278 mg, 1.05 mmol) and triethylamine (0.3 mL). The reaction mixture was stirred for 60 hr. and water was added. The aqueous solution was washed with methylene chloride (2×). The combined organic layers were dried (sodium sulfate), filtered, and concentrated in vacuo. The crude product was purified via radial chromatography using a solvent gradient (methylene chloride to 5% methanol/methylene chloride) to obtain the title compound of Step A.
Reaction SMILES: C1C[O:4][CH2:3][CH2:2]1.[CH3:6][C@@:7]12[C@H:16]3[CH2:17][CH2:18][C@:19]4([CH3:30])[C:23]([C:24]5[CH:25]=[CH:26][CH:27]=[N:28][CH:29]=5)=[CH:22][CH2:21][C@H:20]4[C@@H:15]3[CH2:14][CH:13]=[C:12]1[CH2:11][C@@H:10]([OH:31])[CH2:9][CH2:8]2.C(N(CC)CC)C.C(OC(=O)C)(=O)C>CN(C)C1C=CN=CC=1.O.C1(C)C=CC=CC=1>[CH3:2][C:3]([O:31][C@@H:10]1[CH2:11][C:12]2[C@@:7]([CH3:6])([C@@H:16]3[C@@H:15]([CH2:14][CH:13]=2)[C@@H:20]2[CH2:21][CH:22]=[C:23]([C:24]4[CH:25]=[CH:26][CH:27]=[N:28][CH:29]=4)[C@@:19]2([CH3:30])[CH2:18][CH2:17]3)[CH2:8][CH2:9]1)=[O:4]
Reactant: C1CCOC1
Reactant: C[C@]12CC[C@H](O)CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@@H]3[C@@H]2CC[C@]2(C)C(c4cccnc4)=CC[C@@H]32)C1
Temperature: 22.5 °C
Reaction time: 24 h
Yield: 90 %

Procedure:
1 l of THF was added to 100 g of abiraterone (0.286 mole). 44 g (1.5 eq.) of triethylamine, 1.75 g of 4-dimethylaminopyridine (2 molar %) and 35 g (1.2 eq.) of acetic anhydride were added to the slurry. The slurry was stirred for 24 hours at 20-25° C. (the mixture turned to solution at the end of the reaction which was monitored by HPLC). 0.7 l of toluene and 0.4 l of water were added to the mixture which was stirred for 1 h at 20-25° C. The mixture was clarified on a cake of Clarcel®. The two layers were separated and the organic layer was washed with 0.1 l of water. The organic layer was concentrated at 40° C. to dryness under vacuum. 100 ml of ethanol and 900 ml of n-hexane were then added and the mixture was heated to 55-60° C. to dissolve (the solution was still cloudy). 5 wt % of 2S activated charcoal and 5 wt % of Clarcel® were added to the mixture which was maintained 30 minutes at 55-60° C. The Clarcel® and the charcoal were then filtered at 55-60° C. and washed twice with 0.1 l of ethanol. The ethanol was then partially removed by distillation under vacuum at 40±5° C. The mixture was cooled to 20° C., then to 0-5° C. and maintained 1 hour at this temperature. The suspension was filtered and the cake was washed twice with 0.1 l of n-hexane at 0-5° C. The wet abiraterone acetate was dried at 50° C. under vacuum to give 90 g (0.23 mole) of the pure abiraterone acetate (up to 99.0% by HPLC) 90% yield from the abiraterone. The overall yield from DHEA was around 43-45%.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[Si]([C:18]([F:21])([F:20])[F:19])(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[F:19][C:18]([F:21])([F:20])[C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)([OH:3])[CH3:2]
Reactant: COC(=O)c1ccc(C(C)=O)cc1
Reactant: C[Si](C)(C)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C(C)(O)C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a 3 L flask containing methyl 4-acetylbenzoate (60 g, 0.34 mol, 1.0 equiv) in 1.0 L THF was added 96.6 g TMS-CF3 (0.68 mol, 2.0 equiv) at 0° C. The solution was allowed to stir for 30 min, followed by the dropwise addition of 680 mL tetrabutylammonium fluoride (1.0M in THF, 0.68 mol, 2.0 equiv) via addition funnel over a period of 3 h. After the addition was complete, the solution was allowed to stir for an additional 30 min and warm to room temperature. The solution was then concentrated down under reduced pressure. Then the mixture was diluted with Sat. NaHCO3 and extracted (4×10% MeOH/CH2Cl2). The organics were combined, dried (MgSO4), and concentrated under reduced pressure. Purification by flash chromatography (SiO2, 15% EtOAc/Hexanes) gave the product as an orange oil.
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][N:15]=1.[Li+].CC([N-]C(C)C)C.[CH2:29]([Si:31]([CH2:35][CH3:36])([CH2:33][CH3:34])Cl)[CH3:30]>C1COCC1>[Br:13][C:14]1[CH:19]=[C:18]([Si:31]([CH2:35][CH3:36])([CH2:33][CH3:34])[CH2:29][CH3:30])[C:17]([F:20])=[CH:16][N:15]=1
Reactant: CC[Si](Cl)(CC)CC
Reactant: Fc1ccc(Br)nc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CC[Si](CC)(CC)c1cc(Br)ncc1F
Yield: 96 %

Procedure:
To a solution of diisopropylamine (25.3 g, 250 mmol) in THF (400 ml) was added n-BuLi (100 ml, 2.5 mol/L in hexanes) below −50° C. A solution of 2-bromo-5-fluoropyridine (41.9 g, 238 mmol) in THF (60 ml) was added to the LDA-solution at −78° C. in a dropwise manner below −63° C. After 60 minutes at −78° C. triethylchlorosilane (44 ml, 262 mmol) was added in a fast manner keeping the temperature below −50° C. The cooling bath was removed and the reaction mixture was allowed to reach −20° C. The reaction mixture was poured on a mixture of 1M aq. HCl (250 ml) and aq. NH4Cl (10%). Tert.-butyl methyl ether was added and the layers were separated. The organic phase was washed with brine, dried over magnesium sulfate, filtered and evaporated to give a yellow liquid. Distillation (bp. 99-101° C., 0.5 mmHg). afforded the title compound as a slightly yellow liquid: 66.26 g (96% yield).
Reaction SMILES: [N+:1]([C:4]1[C:5]([C:9]([OH:11])=O)=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].[NH2:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[C:22]([O:21][C:19]([N:16]1[CH2:17][CH2:18][CH:13]([NH:12][C:9]([C:5]2[C:4]([N+:1]([O-:3])=[O:2])=[CH:8][NH:7][N:6]=2)=[O:11])[CH2:14][CH2:15]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]
Reactant: O=C(O)c1n[nH]cc1[N+](=O)[O-]
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: CC(C)(C)OC(=O)N1CCC(NC(=O)c2n[nH]cc2[N+](=O)[O-])CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 241.9 %

Procedure:
4-Nitropyrazole-3-carboxylic acid (7.3 g; 15.9 mmol) was added to a stirred solution of 4-amino-1-Boc-piperidine (10.2 mg; 51 mmol), EDC (10.7 g; 55.8 mmol), and HOAt (55.8 g; 19.1 mmol) in DMF (100 ml), and then stirred at room temperature overnight. The solvent was removed by evaporation under reduced pressure and the residue triturated with water (250 ml). The resultant cream solid was collected by filtration, washed with water then dried under vacuum to give 13.05 g of 4-[(4-nitro-1H-pyrazole-3-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (LC/MS: Rt 2.50, [M+H]+ 340).
Reaction SMILES: [CH:1]1([O:7][C:8]2[CH:9]=[C:10]([C:16]3[O:17][CH:18]=[C:19]([CH2:21][CH2:22][C:23]([C:25]4[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=4)=[O:24])[N:20]=3)[CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[CH2:6][CH2:5][CH2:4][CH:3]=[CH:2]1>C(O)C.[C].[Pd]>[CH:1]1([O:7][C:8]2[CH:9]=[C:10]([C:16]3[O:17][CH:18]=[C:19]([CH2:21][CH2:22][C:23]([C:25]4[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=4)=[O:24])[N:20]=3)[CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COc1ccc(-c2nc(CCC(=O)c3ncccc3C)co2)cc1OC1C=CCCC1
Agent: [Pd]
Solvent: CCO
Product: COc1ccc(-c2nc(CCC(=O)c3ncccc3C)co2)cc1OC1CCCCC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 0.3 g quantity of 3-{2-[3-(2-cyclohexenyloxy)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propan-1-one obtained in Example 157 was dissolved in 20 ml of ethanol. A 50 mg quantity of 10% palladium-carbon powder was added thereto, and the mixture was stirred at room temperature for 2 hours. The catalyst was removed by filtration, and the filtrate was then concentrated. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1) to give 0.2 g of pale yellow oily 3-[2-(3-cyclohexyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propan-1-one.
Reaction SMILES: [CH2:1]([N:3]([CH2:28][CH3:29])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:12]2[C:21]([C:22]([OH:24])=O)=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)=[O:11])=[C:6]([O:25][CH2:26][CH3:27])[CH:5]=1)[CH3:2].[CH3:30][C:31]1[C:32]2[N:33]([CH:37]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[N:39]=2)[CH:34]=[CH:35][CH:36]=1.C(OC(=O)C)(=O)C>C1(C)C=CC=CC=1>[CH2:1]([N:3]([CH2:28][CH3:29])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:37]3[N:33]4[CH:34]=[CH:35][CH:36]=[C:31]([CH3:30])[C:32]4=[N:39][C:38]=3[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:12]3[C:21](=[N:20][C:19]4[C:14]([N:13]=3)=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:22](=[O:24])[O:11]2)=[C:6]([O:25][CH2:26][CH3:27])[CH:5]=1)[CH3:2]
Reactant: Cc1cccn2cc(-c3ccccc3)nc12
Reactant: CCOc1cc(N(CC)CC)ccc1C(=O)c1nc2ccccc2nc1C(=O)O
Solvent: CC(=O)OC(C)=O
Solvent: Cc1ccccc1
Product: CCOc1cc(N(CC)CC)ccc1C1(c2c(-c3ccccc3)nc3c(C)cccn23)OC(=O)c2nc3ccccc3nc21

Procedure:
A mixture of 3.9 grams of (4-diethylamino-2-ethoxyphenyl)(3-carboxyquinoxalin-2-yl)ketone, 2.1 grams of 8-methyl-2-phenylimidazo[1,2-a]pyridine and 15 ml. of acetic anhydride was heated at 80° C. for 1 hour and poured into a mixture of ice ammonia and toluene. The toluene portion was separated, washed with saturated sodium sulfate solution, filtered through phase separation paper and concentrated. Petroleum ether was added to the concentrate and 2.7 grams of crystalline material was filtered off. This material was recrystallized four times from a mixture of toluene and petroleum ether to yield a final product with a melting point of 135°-136° C. A solution of the product produced a blue color when applied to a record sheet material coated with a zinc-modified phenolic resin or silton clay.