Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N)CN.[C:5]([O:9][C:10](=[O:42])[NH:11][CH2:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([NH:19][C:20]([C:22]2[C:30]3[N:29]4[CH:31]=[N:32][N:33]=[C:28]4[CH:27]=[N:26][C:25]=3[N:24](COCC[Si](C)(C)C)[CH:23]=2)=[O:21])[CH2:15][CH2:14]1)([CH3:8])([CH3:7])[CH3:6].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:5]([O:9][C:10](=[O:42])[NH:11][CH2:12][C@H:13]1[CH2:14][CH2:15][C@H:16]([NH:19][C:20]([C:22]2[C:30]3[N:29]4[CH:31]=[N:32][N:33]=[C:28]4[CH:27]=[N:26][C:25]=3[NH:24][CH:23]=2)=[O:21])[CH2:17][CH2:18]1)([CH3:8])([CH3:6])[CH3:7]
Reactant: CC(C)(C)OC(=O)NC[C@H]1CC[C@H](NC(=O)c2cn(COCC[Si](C)(C)C)c3ncc4nncn4c23)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: NCCN
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC[C@H]1CC[C@H](NC(=O)c2c[nH]c3ncc4nncn4c23)CC1
Temperature: 60 °C
Reaction time: 24 h

Procedure:
Ethylenediamine (0.011 mL, 0.16 mmol) was added to a solution of tert-butyl(trans-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-8-carboxamido)cyclohexyl)methylcarbamate (0.043 g, 0.079 mmol, prepared using Z from Preparation #AAAAA.1 and KOH, H with tert-butyl trans-4-aminocyclohexylmethylcarbamate [AMRI], HATU, and TEA) in THF (1 mL). TBAF (1.0 M solution in THF, 0.470 mL, 0.470 mmol) was added in one portion. The mixture was heated at about 60° C. After about 24 h, the solution was allowed to cool to ambient temperature and stirred for about 40 h. The volatiles were removed under reduced pressure. The residue was slurried in water (10 mL) and extracted with EtOAc (4×20 mL). The combined organic portions were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 2-10% MeOH/DCM to give tert-butyl(trans-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-8-carboxamido)cyclohexyl)methylcarbamate (0.0094 g, 29%): LC/MS (Table 1, Method n) Rt=0.55 min; MS m/z: 414 (M+H)+.
Reaction SMILES: [C:1]([O:5][CH:6]([C:11]1[C:12]([CH3:28])=[N:13][C:14]2[N:15]([N:18]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[CH:20]=2)[C:16]=1Cl)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[F:29][C:30]1[CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[C:33]([CH3:40])=[C:34]2[C:39]=1[O:38][CH2:37][CH2:36][CH2:35]2.C([O-])([O-])=O.[K+].[K+]>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.CN(C=O)C>[C:1]([O:5][CH:6]([C:11]1[C:12]([CH3:28])=[N:13][C:14]2[N:15]([N:18]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[CH:20]=2)[C:16]=1[C:32]1[C:33]([CH3:40])=[C:34]2[C:39](=[C:30]([F:29])[CH:31]=1)[O:38][CH2:37][CH2:36][CH2:35]2)[C:7]([O:9][CH3:10])=[O:8])([CH3:3])([CH3:4])[CH3:2]
Reactant: Cc1c(B2OC(C)(C)C(C)(C)O2)cc(F)c2c1CCCO2
Reactant: COC(=O)C(OC(C)(C)C)c1c(C)nc2cc(-c3cccc(Cl)c3)nn2c1Cl
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: [K+]
Solvent: CN(C)C=O
Product: COC(=O)C(OC(C)(C)C)c1c(C)nc2cc(-c3cccc(Cl)c3)nn2c1-c1cc(F)c2c(c1C)CCCO2
Temperature: 115 °C
Yield: 48.9 %

Procedure:
To a 2-5 ml microwave tube was added methyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (200 mg, 0.474 mmol), tetrakis(triphenylphosphine)palladium(0) (55 mg, 0.047 mmol), 2-(8-fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (180 mg, 0.616 mmol), DMF (3 mL), followed by 2M K2CO3 solution (300 μl). The reaction mixture was heated in a microwave reactor at 115° C. for 45 min. The reaction mixture was filtered and the filtrate was purified by silica gel chromatography to afford (128 mg, 48.9%) of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.82 (s, 1H), 7.76-7.65 (m, 1H), 7.41-7.29 (m, 2H), 7.01-6.73 (m, 2H), 5.02 (s, 1H), 4.37 (dt, J=6.5, 3.5 Hz, 2H), 3.66 (s, 3H), 2.93-2.69 (m, 5H), 2.21 (dd, J=5.6, 2.4 Hz, 2H), 1.86 (s, 3H), 1.18 (s, 9H).
Reaction SMILES: [F:1][CH2:2][C:3]([N:17]1[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]2[C:18]1=[O:27])([CH2:6][CH2:7][CH2:8][O:9]CC1C=CC=CC=1)[C:4]#[N:5].[Si](I)(C)(C)C>ClCCl>[F:1][CH2:2][C:3]([N:17]1[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]2[C:18]1=[O:27])([CH2:6][CH2:7][CH2:8][OH:9])[C:4]#[N:5]
Reactant: N#CC(CF)(CCCOCc1ccccc1)N1C(=O)c2ccccc2C1=O
Agent: C[Si](C)(C)I
Solvent: ClCCl
Product: N#CC(CF)(CCCO)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 114.9 %

Procedure:
To a solution of 2-fluoromethyl-2-phthalimido-5-benzyloxypentanenitrile (49.4 g) in dry dichloromethane (400 ml) is added TMSI (45 ml, 2.2 equivalents), and the mixture is stirred at room temperature overnight. The solvent is removed under vacuum. The residue is evaporated two times more with dichloromethane and then dissolved in chloroform. After addition of triethylamine (60 ml), the mixture is refluxed for 3 hours. Washing with water, 1N HCl (2×), water again, drying, and evaporation gives 2-fluoromethyl-2-phthalimido-5-hydroxypentanenitrile as a brown oil (42.8 g).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[OH:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[CH:39]=[N:38][CH:37]=[CH:36]2.[CH3:43][N:44]1[CH:48]2[CH2:49][CH:50](O)[CH2:51][CH:45]1[CH2:46][CH2:47]2>ClCCl.C(N(CC)CC)C>[CH3:43][N:44]1[CH:48]2[CH2:47][CH2:46][CH:45]1[CH2:51][CH:50]([O:32][C:33]1[CH:34]=[C:35]3[C:40](=[CH:41][CH:42]=1)[CH:39]=[N:38][CH:37]=[CH:36]3)[CH2:49]2
Reactant: Oc1ccc2cnccc2c1
Reactant: CN1C2CCC1CC(O)C2
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN1C2CCC1CC(Oc1ccc3cnccc3c1)C2
Reaction time: 0.33 h
Yield: 18 %

Procedure:
625 mg of triphenyl phosphine were dissolved in 20 mL of dry dichloromethane, 0.095 mL of diethyl azodicarboxylate were added and the solution was shaken for 20 minutes. 69 μL of triethyl amine, 72.6 mg of 6-hydroxy isoquinoline and 67.1 mg of tropine were added and the mixture was shaken overnight. The reaction mixture was filtered, the remainders washed thoroughly with dichloromethane and the combined organic layer was extracted twice with 1N sodium hydroxide and water, respectively. The organic layer was dried, evaporated to dryness and the crude material was purified by HPLC. The product was dissolved in 2N HCl and lyophilized to give 23 mg of 6-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-isoquinoline (52) as the hydrochloride. Rt=0.52 min (Method A). Detected mass: 269.2 (M+H+).
Reaction SMILES: [C:1]([CH2:6][CH2:7][S:8]([O-:11])(=O)=[O:9])([O:3][CH2:4][CH3:5])=[O:2].[Na+].P(Cl)(Cl)(Cl)(Cl)[Cl:14]>C(Cl)(Cl)Cl>[C:1]([CH2:6][CH2:7][S:8]([Cl:14])(=[O:11])=[O:9])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: CCOC(=O)CCS(=O)(=O)[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CCOC(=O)CCS(=O)(=O)Cl
Yield: 32.2 %

Procedure:
To a stirred mixture of 90.5 g (0.44 moles) sodium 2-carboethoxyethyl sulfonate (the product of Example 26) in 300 ml chloroform, 92 g (0.44 moles) phosphorus pentachloride was added in small portions, maintaining the temperature of the reaction mixture below 40° C. during the addition. The reaction mixture was refluxed for about 6 hours, and then filtered. Nitrogen was bubbled through the solution to remove excess hydrogen chloride gas. Stripping of the solvent gave 28.4 g of the above-identified product.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH2:12][N:13]([CH3:15])[CH3:14])=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2.CN(C=O)C.[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[S:29](Cl)(=[O:31])=[O:30]>>[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[S:29]([N:8]1[C:9]2[C:5](=[C:4]([CH2:12][N:13]([CH3:14])[CH3:15])[C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[CH:6]=[CH:7]1)(=[O:31])=[O:30]
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1Cl
Reactant: COc1ccc2[nH]ccc2c1CN(C)C
Solvent: CN(C)C=O
Product: COc1ccc2c(ccn2S(=O)(=O)c2ccc(Cl)cc2Cl)c1CN(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 17.3 %

Procedure:
To a solution of 1-(5-methoxy-1H-indol-4-yl)-N,N-dimethylmethanamine (15 mg, 0.07 mmol; Intermediate 97) in DMF (1 mL) NaH (4 mg, 0.15 mmol) was added at rt. The reaction mixture was stirred at rt for 15 min and 2,4-dichlorobenzenesulphonyl chloride (27 mg, 0.11 mmol) was added. The reaction mixture was allowed to stir at rt over night. The reaction was quenched by addition of water. Purification by preparative HPLC/UV (System B) afforded the title product (5 mg, 17%) as a white solid. MS (ESI+) for C18H18Cl2N2O3S m/z 414 (M+H)+.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:8]=[CH:7][C:6]2=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:5]2[N:4]=1.C(Cl)Cl.C1C=C(Cl)C=C(C(OO)=[O:30])C=1>>[CH3:1][S:2]([C:3]1[N:8]=[CH:7][C:6]2=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:5]2[N:4]=1)=[O:30]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1ncc2ccc(-c3ccccc3O)n2n1
Solvent: ClCCl
Product: CS(=O)c1ncc2ccc(-c3ccccc3O)n2n1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 59 %

Procedure:
2-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenol (1.915 g, 7.442 mmol) and Methylene chloride (50 mL, 800 mmol) were combined in a flask. m-CPBA 70-75% (70:30, m-Chloroperbenzoic acid:3-Chlorobenzoic acid, 1.835 g, 7.444 mmol) was added over 10 minutes. The reaction was stirred at room temperature for 10 minutes. Reaction was concentrated and purified by normal phase silica gel chromatography eluting with ethyl acetate to obtain a brown solid, 2-(2-Methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenol (1.2 g, 60%). LCMS: m/z=274.01 (M+H+); 1H NMR (400 MHz, DMSO-d6) δ 9.98 (br s, 1H), 9.29 (s, 1H), 7.80 (m, 1H), 7.46 (d, 1H, J=4.7 Hz), 7.30 (m, 2H), 7.03 (d, 1H, J=8.2 Hz), 6.96 (m, 1H), 2.93 (s, 3H).
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]([OH:15])=[O:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1>[C:2]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:12]1)=[O:7])([CH3:1])([CH3:3])[CH3:4]
Reactant: BrCc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)C1
Solvent: C1CCC2=NCCCN2CC1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC(C(=O)OCc2ccccc2)C1
Reaction time: 12 h

Procedure:
To a solution of 1.00 g Boc-1-pyrrolidine-3-carboxylic acid in 10 ml toluene were added 0.61 ml benzyl bromide and 0.76 ml DBU. After stirring for 12 h the reaction mixture was washed with water and the crude product obtained after evaporation of the solvent was purified by flash chromatography on silica using ethyl acetate/heptane 1:3 as eluent.
Reaction SMILES: [CH2:1]([O:8][C:9]1[N:14]=[C:13]([CH:15]=[O:16])[CH:12]=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)([OH:22])N.[O-]Cl=O.[Na+].CCOC(C)=O>CC(C)=O.O.CCCCCC>[CH2:1]([O:8][C:9]1[N:14]=[C:13]([C:15]([OH:22])=[O:16])[CH:12]=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1ccc([N+](=O)[O-])c(OCc2ccccc2)n1
Reactant: NS(=O)(=O)O
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CC(C)=O
Product: O=C(O)c1ccc([N+](=O)[O-])c(OCc2ccccc2)n1
Temperature: 0 °C

Procedure:
To a cooled (0° C.) stirred mixture of 6-(benzyloxy)-5-nitropicolinaldehyde (0.5 g, 0.0019 mol) in acetone:water (1:1, 5 mL), was added sulphamic acid (280 mg, 0.00029 mol, Aldrich) and NaClO2 (260 mg, 0.00029 mol, Aldrich). The reaction mixture was stirred for 2 h at the same temperature. After completion of the reaction (monitored by TLC, 10% EtOAc in hexane), the reaction mixture was quenched with water (2 mL) and extracted with EtOAc (20 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, and purified by column chromatography, silica gel (60-120 mesh) using 5-9% EtOAc in petroleum ether as an eluent to give the title compound. 1H NMR (400 MHz, CDCl3) δ: 13.80 (br. s., 1H), 8.45 (d, J=8.1 Hz, 1H), 7.96 (d, J=8.1 Hz, 1H), 7.51 (d, J=7.2 Hz, 2H), 7.44-7.36 (m, 3H), 5.62 (s, 2H).
Reaction SMILES: [F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][CH2:17][CH:16]([C:19](O)=[O:20])[C:15]3=[O:22])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[NH3:25]>>[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][CH2:17][CH:16]([C:19]([NH2:25])=[O:20])[C:15]3=[O:22])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: O=C(O)C1CCN(c2ccc(OCc3ccc(F)cc3)cc2)C1=O
Reactant: N
Product: NC(=O)C1CCN(c2ccc(OCc3ccc(F)cc3)cc2)C1=O

Procedure:
The title compound is prepared in analogy to Example 3d) from (RS)-1-[4-(4-fluoro-benzyloxy)-phenyl]-2-oxo-pyrrolidine-3-carboxylic acid and ammonia. Yield: 18% of a brownish solid. MS: m/e=329.3 (M++H).
Reaction SMILES: [CH:1]([N:4]1[CH2:14][CH:13]2[CH2:15][CH2:16][CH:6]([C:7]3[C:12]2=[CH:11][C:10]([NH2:17])=[CH:9][CH:8]=3)[CH2:5]1)([CH3:3])[CH3:2].Cl[C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32]([NH:35][CH3:36])(=[O:34])=[O:33])[C:22]([Cl:37])=[CH:21][N:20]=1>>[Cl:37][C:22]1[C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32]([NH:35][CH3:36])(=[O:34])=[O:33])=[N:24][C:19]([NH:17][C:10]2[CH:11]=[C:12]3[C:7](=[CH:8][CH:9]=2)[CH:6]2[CH2:16][CH2:15][CH:13]3[CH2:14][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5]2)=[N:20][CH:21]=1
Reactant: CC(C)N1CC2CCC(C1)c1cc(N)ccc12
Reactant: CNS(=O)(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Product: CNS(=O)(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2)C2CCC3CN(C(C)C)C2)ncc1Cl

Procedure:
2-[5-Chloro-2-(10-isopropyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzenesulfonamide was prepared from 10-isopropyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamine and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzenesulfonamide in an analogous manner to Example 273. Product isolated as a clear thin film (21 mg, 33%). LCMS (m/e) 527 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 9.13 (s, 1H), 8.48 (d, 1H, J=8.3 Hz), 7.99 (s, 1H), 7.94 (dd, 1H, J=1.5 and 8.0 Hz), 7.58-7.51 (m, 1H), 7.26-7.19 (m, 3H), 7.08 (s, 1H), 6.98 (dd, 1H, J=3.4 and 5.3 Hz), 5.21 (bs, 1H), 3.00-2.90 (m, 1H), 2.89-2.77 (m, 4H), 2.62 (d, 3H, J=2.7 Hz), 2.31 (d, 2H, J=11.0 Hz), 2.16 (d, 2H, J=8.1 Hz), 1.55 (d, 2H, J=8.2 Hz), 0.94 (d, 6H, J=6.6 Hz).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[NH:10][C:9](=[O:12])[O:8][C:7]([CH3:14])([CH3:13])[C:6]=2[CH:5]=[C:4]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][S:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[CH:3]=1.[OH:28]O>>[Cl:27][C:24]1[CH:23]=[CH:22][C:21]([S:20]([CH2:19][CH2:18][CH2:17][CH2:16][O:15][C:4]2[CH:3]=[C:2]([Cl:1])[C:11]3[NH:10][C:9](=[O:12])[O:8][C:7]([CH3:14])([CH3:13])[C:6]=3[CH:5]=2)=[O:28])=[CH:26][CH:25]=1
Reactant: CC1(C)OC(=O)Nc2c(Cl)cc(OCCCCSc3ccc(Cl)cc3)cc21
Reactant: OO
Product: CC1(C)OC(=O)Nc2c(Cl)cc(OCCCCS(=O)c3ccc(Cl)cc3)cc21

Procedure:
Prepared analogously to Example 2 from 8-chloro-6-[4-(4-chloro-phenylmercapto)-butoxy]-4,4-dimethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [C:1]([C:3]1[C:4](=O)[NH:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2].P(Cl)(Cl)([Cl:16])=O.CCCCCC>C(Cl)Cl>[Cl:16][C:4]1[C:3]([C:1]#[N:2])=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1
Reactant: N#Cc1cc2ccccc2[nH]c1=O
Reactant: O=P(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCCCCC
Product: N#Cc1cc2ccccc2nc1Cl

Procedure:
A mixture of 50 g of 3-cyano-2(1H)-quinolinone and 250 ml of phosphoryl chloride was heated at reflux for 18 hours. Volatile material was evaporated from the mixture under reduced pressure and the resulting residue was carefully added to water. The solid which formed was separated by filtration, washed with water and dried to give crude product. This was dissolved in methylene chloride and the resulting solution was treated with silica gel and filtered to give a pale yellow solution. Hexane was added to the solution which was then placed on a steam bath until crystallization occurred. The solid was then separated by filtration to give 2-chloro-3-cyanoquinoline. This compound melts at about 163°-164° C.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][N:5]([CH2:8][CH2:9][C@@:10]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[C:11]([NH:13][O:14][C@@H:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)=[O:12])[C:4](=[O:26])[CH:3]=1.[F:27][C:28]1[CH:29]=[C:30]([CH:46]=[CH:47][C:48]=1B1OC(C)(C)C(C)(C)O1)[O:31][CH2:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([O:39][CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][O:41]2)[CH2:35][CH2:34]1.C[C@@](S(C)(=O)=O)(CCN1C=CC(C2C=CC(OC[C@H]3CC[C@@H](OC4CCCCO4)CC3)=CC=2)=CC1=O)C(NOC1CCCCO1)=O>>[F:27][C:28]1[CH:29]=[C:30]([O:31][CH2:32][C@H:33]2[CH2:38][CH2:37][C@H:36]([O:39][CH:40]3[CH2:45][CH2:44][CH2:43][CH2:42][O:41]3)[CH2:35][CH2:34]2)[CH:46]=[CH:47][C:48]=1[C:2]1[CH:7]=[CH:6][N:5]([CH2:8][CH2:9][C@@:10]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[C:11]([NH:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)=[O:12])[C:4](=[O:26])[CH:3]=1
Reactant: C[C@@](CCn1ccc(I)cc1=O)(C(=O)NO[C@@H]1CCCCO1)S(C)(=O)=O
Reactant: CC1(C)OB(c2ccc(OC[C@H]3CC[C@H](OC4CCCCO4)CC3)cc2F)OC1(C)C
Agent: C[C@@](CCn1ccc(-c2ccc(OC[C@H]3CC[C@@H](OC4CCCCO4)CC3)cc2)cc1=O)(C(=O)NOC1CCCCO1)S(C)(=O)=O
Product: C[C@@](CCn1ccc(-c2ccc(OC[C@H]3CC[C@H](OC4CCCCO4)CC3)cc2F)cc1=O)(C(=O)NOC1CCCCO1)S(C)(=O)=O

Procedure:
The title compound (366 mg, 65.5 mmol) was prepared from (2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-[(2R)-tetrahydro-2H-pyran-2-yloxy]butanamide (0.410 g, 8.23 mmol) and (+/−)-2-[(trans-4-{[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}cyclohexyl)oxy]tetrahydro-2H-pyran (0.358 g, 8.23 mmol) by a procedure analogous to that described for (2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(4-{[cis-4-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]methoxy}phenyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide Example 8, Step E. LCMS m/z 677.8 (M−1)
Reaction SMILES: [C:1]1([C:7](=[C:14]2[CH2:19][CH2:18][N:17]([C:20](=[O:36])[C:21]([C:23]3[C:31]4[C:26](=[C:27]([O:34][CH3:35])[N:28]=[CH:29][C:30]=4[O:32][CH3:33])[NH:25][CH:24]=3)=[O:22])[CH2:16][CH2:15]2)[C:8]#[C:9][Si](C)(C)C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+]>CO>[C:1]1([C:7](=[C:14]2[CH2:15][CH2:16][N:17]([C:20](=[O:36])[C:21]([C:23]3[C:31]4[C:26](=[C:27]([O:34][CH3:35])[N:28]=[CH:29][C:30]=4[O:32][CH3:33])[NH:25][CH:24]=3)=[O:22])[CH2:18][CH2:19]2)[C:8]#[CH:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COc1ncc(OC)c2c(C(=O)C(=O)N3CCC(=C(C#C[Si](C)(C)C)c4ccccc4)CC3)c[nH]c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#CC(=C1CCN(C(=O)C(=O)c2c[nH]c3c(OC)ncc(OC)c23)CC1)c1ccccc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 91 %

Procedure:
To a solution of 1-[4-(1-phenyl-1-(2-trimethylsilylethyn-1-yl)-methylene)-piperidin-1-yl]-2-(4,7-dimethoxy-6-azaindol-3-yl)-ethane-1,2-dione (0.035 g, 0.0699 mmol) in MeOH (1 mL) was added K2CO3 (0.010 g, 0.0724 mmol) and the mixture was allowed to stir at room temperature for 6 h. The mixture was then evaporated and the residue was purified by preparative HPLC to give the title compound as a colorless solid (0.027. g, 91%).
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C=CC(S(O)(=O)=O)=C(N)C=2)=[CH:4][C:3]=1Br.N1C(Cl)=NC(Cl)=NC=1Cl.NC1C=C(S(O)(=O)=O)C=CC=1>>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Nc1cc(Sc2cc(Br)c(N)c3c2C(=O)c2ccccc2C3=O)ccc1S(=O)(=O)O
Agent: Clc1nc(Cl)nc(Cl)n1
Agent: Nc1cccc(S(=O)(=O)O)c1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
1-Amino-2-bromo-4-(3'-amino-4'-sulfophenylthio)anthraquinone (10.1 parts), cyanuric chloride (3.7 parts) and 1-aminobenzene-4-β-sulfatoethylsulfone (5.6 parts) were subjected to condensation reactions one after another in an aqueous medium in a usual manner, followed by condensation reaction with 3-aminobenzenesulfonic acid (3.5 parts) at 50° to 70° C. under a weak acid condition. Thereafter, salting out of the reaction mixture gave an anthraquinone compound of the following formula (free aci form). ##STR322##
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[S:3]([CH:6]([S:10]([C:13]([F:16])([F:15])[F:14])(=[O:12])=[O:11])[CH2:7][CH:8]=[CH2:9])(=[O:5])=[O:4].[CH2:19]([O:21][SiH:22]([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[CH3:20]>C1CC=CCCC=C1.Cl[Pt]Cl.C1(C)C=CC=CC=1>[F:14][C:13]([F:15])([F:16])[S:10]([CH:6]([S:3]([C:2]([F:17])([F:1])[F:18])(=[O:4])=[O:5])[CH2:7][CH2:8][CH2:9][Si:22]([O:26][CH2:27][CH3:28])([O:23][CH2:24][CH3:25])[O:21][CH2:19][CH3:20])(=[O:12])=[O:11]
Reactant: C=CCC(S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F
Reactant: CCO[SiH](OCC)OCC
Agent: Cl[Pt]Cl
Agent: C1=C\CC/C=C\CC/1
Solvent: Cc1ccccc1
Solvent: C1=CCCC=CCC1
Product: CCO[Si](CCCC(S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F)(OCC)OCC
Reaction time: 11 h
Yield: 65.2 %

Procedure:
A three-necked flask equipped with a reflux condenser and having a volume of 100 ml was charged under nitrogen atmosphere with each of 100.2 g (0.313 mol) of 1,1-bis(trifluoromethanesulfonyl)-3-butene (hereinafter abbreviated as BTSB), 69.8 g of toluene, 11.7 mg (0.0001 parts by mass relative to BTSB) of dichloro(1,5-cyclooctadiene)platinum (II) (made by Tokyo Chemical Industry Co., Ltd.), and 155.0 g (155 parts by mass relative to BTSB) of triethoxysilane (made by Tokyo Chemical Industry Co., Ltd.). After that, under nitrogen atmosphere, it was stirred and mixed for three minutes. Then, the reaction was conducted for 11 hours, while this flask was heated by immersion in an oil bath adjusted to 85° C. After the termination of the reaction, triethoxysilane and toluene were distilled off and recovered under reduced pressure. Then, a distillation under reduced pressure was conducted to carry out a heating at 100° C. to 108° C. and distill it out under a reduced pressure of 533 Pa (4 mmHg), thereby obtaining 98.8 g of 4,4-bis(trifluoromethanesulfonyl)butyltriethoxysilane (hereinafter abbreviated as BTSB-TES).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.C(N1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28])(OCC)=O>C(Cl)Cl>[NH:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([CH2:3][CH2:2][N:1]2[C:22](=[O:23])[C:21]3[C:20](=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:19]2=[O:28])=[CH:5]1
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: NCCc1c[nH]c2ccccc12
Solvent: ClCCl
Product: O=C1c2ccccc2C(=O)N1CCc1c[nH]c2ccccc12

Procedure:
This compound was prepared by the reaction of tryptamine and N-carboethoxyphthalimide: TLC Rf=0.36 (CH2Cl2); MS (ESI+) m/z 291.0.
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH3:15])[CH:11]=2)[NH:6]1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3].O>C1COCC1>[CH3:15][O:14][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[NH:6][CH:5]([CH2:3][OH:2])[CH2:13]2
Reactant: COC(=O)C1Cc2cc(OC)ccc2N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc2c(c1)CC(CO)N2
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.2 %

Procedure:
(RS)-5-methoxy-2,3-dihydro-1H-indole-2-carboxylic acid methyl ester (2.5 g, 12.06 mmol) in THF (130 ml) was added dropwise to a suspension of LiAlH4 in THF (80 ml) at 4° C., and the mixture allowed to stir at RT overnight, and then heated at 65° C. for 4 hr. After cooling, H2O (20 ml) was added cautiously and the mixture stirred 20 min, then filtered and the filtrate extracted with EtOAc (3×50 ml), the extracts were washed with satd. NaCl solution (50 ml), dried (Na2SO4) filtered and evaporated. The crude oil was chromatographed over SiO2 (Merck 230-400 mesh) eluting with CH2Cl2—MeOH (9:1) affording (RS)-(5-methoxy-2,3-dihydro-1H-indol-2-yl)-methanol as a yellow oil (1.41 g, 7.86 mmol, 65%), MS: m/e=179.1 (M+).