Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(C)=O.[N+:5](/[CH:8]=[CH:9]/[C:10]1[S:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)=[CH:13][CH:14]=1)([O-:7])=[O:6].C(O)(=O)C.[BH4-].[Na+]>O>[N+:5]([CH2:8][CH2:9][C:10]1[S:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)=[CH:13][CH:14]=1)([O-:7])=[O:6]
Reactant: Cc1ccc(Oc2ccc(/C=C/[N+](=O)[O-])s2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Solvent: CC(=O)O
Product: Cc1ccc(Oc2ccc(CC[N+](=O)[O-])s2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 47.6 %

Procedure:
To a dimethyl sulfoxide (30.0 mL) solution of 2-((E)-2-nitro-vinyl)-5-p-tolyloxy-thiophene (2.50 g, 9.57 mmol) described in Manufacturing Example 48-1-3 and acetic acid (2.50 mL) was added sodium borohydride (610 mg, 20.6 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 30 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:4) to obtain the title compound (1.20 g, 47.6%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=1.[O:11]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12]1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[O:11]1[CH:15]=[CH:14][C:13]([C:2]2[CH:3]=[CH:4][C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=2)=[CH:12]1
Reactant: OB(O)c1ccoc1
Reactant: CC(=O)c1ccc(Br)cn1
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: CCO
Solvent: Cc1ccccc1
Product: CC(=O)c1ccc(-c2ccoc2)cn1
Temperature: 100 °C
Yield: 74.8 %

Procedure:
To a solution of 1-(5-bromopyridin-2-yl)ethanone (0.5 g, 2.5 mmol) in toluene (10 mL) and ethanol (5 mL) was added furan-3-ylboronic acid (0.335 g, 3.0 mmol) and a 2 M solution of aq. Na2CO3. The reaction mixture was degassed with argon, Pd(PPh3)4 (0.144 g, 0.125 mmol) was added, the reaction mixture was degassed with argon for 10 min, and the reaction was heated to 100° C. for 4 h. The reaction mixture was evaporated under vacuum to remove the ethanol, diluted with water (30 mL), extracted with ethyl acetate (100 mL), dried over sodium sulphate, filtered and evaporated under reduced pressure to obtain crude product. The crude product was purified by Biotage Isolera® One column (using 10% ethyl acetate and hexane) to give 1-(5-(furan-3-yl)pyridin-2-yl)ethanone (0.35 g, 74% yield); 1H NMR (400 MHz, DMSO-d6): δ 9.00 (s, 1H), 8.44 (s, 1H), 8.20-8.17 (m, 1H); 7.95 (d, 1H), 7.83 (s, 1H), 7.13 (s, 1H), 2.57 (s, 3H): LC-MS m/z calcd for [M+H]+ 187.06. found 188.0.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:22]2[C:27](=[O:28])[NH:26][C:25](=[O:29])[C:24]([C:30]#[N:31])=[N:23]2)[CH:5]=[C:6]([Cl:21])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[N:11]([CH2:19][OH:20])[N:10]=1.[C:32]1(=[O:38])[O:37][C:35](=[O:36])[CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>C(Cl)Cl>[Cl:21][C:6]1[CH:5]=[C:4]([N:22]2[C:27](=[O:28])[NH:26][C:25](=[O:29])[C:24]([C:30]#[N:31])=[N:23]2)[CH:3]=[C:2]([Cl:1])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[N:11]([CH2:19][O:20][C:32](=[O:38])[CH2:33][CH2:34][C:35]([OH:37])=[O:36])[N:10]=1
Reactant: O=C1CCC(=O)O1
Reactant: CC(C)c1cc(Oc2c(Cl)cc(-n3nc(C#N)c(=O)[nH]c3=O)cc2Cl)nn(CO)c1=O
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)c1cc(Oc2c(Cl)cc(-n3nc(C#N)c(=O)[nH]c3=O)cc2Cl)nn(COC(=O)CCC(=O)O)c1=O
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 24 %

Procedure:
A solution of 2-[3,5-dichloro-4-(1-hydroxymethyl-5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (200 mg, 0.42 mmol), 4-N,N-dimethyaminopyridine (2.6 mg, 0.02 mmol) and succinic anhydride (47 mg, 0.47 mmol) in methylene chloride (2.53 mL) at 25° C. was treated with N,N-diisopropylethylamine (0.17 mL, 0.98 mmol). The reaction mixture was stirred at 25° C. for 3.5 h. At this time, the reaction mixture was poured onto a saturated aqueous ammonium chloride solution (100 mL) and was then extracted with a 90/10 methylene chloride/methanol solution (3×100 mL). The pH of the aqueous layer was brought to pH=2 with a few drops of a 2N aqueous hydrochloric acid solution and was then extracted with a 90/10 methylene chloride/methanol solution (1×100 mL). The combined organics were dried over sodium sulfate, filtered, rinsed and concentrated in vacuo. ISCO CombiFlash chromatography (12 g, 0.5-4% methanol/methylene chloride) followed by supercritical fluid chromatography (Daicel OJ column, 30% methanol) afforded succinic acid mono-{3-[2,6-dichloro-4-(6-cyano-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-5-isopropyl-6-oxo-6H-pyridazin-1-ylmethyl}ester (57 mg, 24%) as a light tan solid. ES+-HRMS m/e calcd for C22H18N6O8Cl2 (M+H+) 565.0636, found 565.0633.
Reaction SMILES: [O:1]1[CH:6]([C:7](OCC)=[O:8])[CH2:5][CH2:4][C:3]2[CH:12]=[CH:13][C:14]3[C:19]([C:2]1=2)=[CH:18][CH:17]=[CH:16][CH:15]=3.[NH3:20]>CO>[O:1]1[CH:6]([C:7]([NH2:20])=[O:8])[CH2:5][CH2:4][C:3]2[CH:12]=[CH:13][C:14]3[C:19]([C:2]1=2)=[CH:18][CH:17]=[CH:16][CH:15]=3
Reactant: CCOC(=O)C1CCc2ccc3ccccc3c2O1
Reactant: N
Solvent: CO
Product: NC(=O)C1CCc2ccc3ccccc3c2O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97 %

Procedure:
A mixture of intermediate (10-a) (0.03 mol) in methanol saturated with ammonia (200 ml) was stirred at room temperature overnight. The precipitate was filtered off and washed with methanol. The product was used without further purification, yielding 6.6 g (97%) of (±)-3,4-dihydro-2H-naphtho[1,2-b]pyran-2-carboxamide (interm. 11-a).
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:18]=[CH:17][C:6]2[S:7][C:8]3[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=3[CH:10](O)[CH2:11][C:5]=2[CH:4]=1.[Cl-:21].[Ca+2].[Cl-].Cl>C1C=CC=CC=1>[Cl:21][CH:10]1[C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=2[S:7][C:6]2[CH:17]=[CH:18][C:3]([C:2]([F:20])([F:19])[F:1])=[CH:4][C:5]=2[CH2:11]1
Reactant: [Cl-]
Reactant: OC1Cc2cc(C(F)(F)F)ccc2Sc2ccccc21
Agent: Cl
Agent: [Ca+2]
Solvent: c1ccccc1
Product: FC(F)(F)c1ccc2c(c1)CC(Cl)c1ccccc1S2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
11.4 g of 10,11-dihydro-2-trifluoromethyl-dibenzo[b,f]-thiepin-10-ol 100 ml of benzene and 4 g of calcium chloride are saturated with hydrochloric acid gas for 2 hours at 15° C and subsequently stirred at room temperature for 3 hours. The mixture is filtered and concentrated under reduced pressure. There is obtained 10-chloro-10,11-dihydro-2-trifluoromethyl-dibenzo[b,f]thiepin in the form of yellow crystals.
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[C:39]([CH3:40])=[CH:38][N:37]=[C:36]([CH3:41])[N:35]=2)=[CH:30][CH:29]=1.C1(=O)NC(=O)CC1>C(Cl)(Cl)(Cl)Cl>[Br:8][CH2:40][C:39]1[C:34]([C:31]2[CH:30]=[CH:29][C:28]([Cl:27])=[CH:33][CH:32]=2)=[N:35][C:36]([CH3:41])=[N:37][CH:38]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ncc(C)c(-c2ccc(Cl)cc2)n1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1
Solvent: ClC(Cl)(Cl)Cl
Product: Cc1ncc(CBr)c(-c2ccc(Cl)cc2)n1
Yield: 63.5 %

Procedure:
2.26 g (12.7 mmol) of NBS and 3 mg of dibenzoyl peroxide were added to a solution of 2.73 g (12.5 mmol) of 4-(4-chlorophenyl)-2,5-dimethylpyrimidine in 48 ml of CCl4, and the mixture was refluxed for 5 minutes with stirring and irradiation (cf. Example 25). The NBS had then been converted into succinimide. This was filtered off at room temperature through a filtration aid and washed with CCl4, and the filtrate was evaporated in vacuo. The residue was dissolved in about 60 ml of diisopropyl ether/n-pentane 1:1, the slightly turbid solution was clarified using kieselguhr and again filtered under suction, and the clear filtrate was evaporated in an oil-pump vacuum to constant weight. According to the 1H NMR spectrum, the residue (3.4 g) comprised 69.5% purity 5-bromomethyl-4-(4-chlorophenyl)-2-methylpyrimidine (=63.5% yield). This bromomethyl compound was used in this form for the reaction with 1-(4-hydroxyphenyl)piperazine (cf. Example 23, No. 5.19).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:5]=1[NH2:19])([O-:3])=[O:2].Br[C:21]1[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:24]=[CH:23][C:22]=1[F:31].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.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>[F:31][C:22]1[C:21]([C:8]2[CH:7]=[CH:6][C:5]([NH2:19])=[C:4]([N+:1]([O-:3])=[O:2])[CH:9]=2)=[C:26]([C:27]([F:28])([F:29])[F:30])[CH:25]=[CH:24][CH:23]=1
Reactant: CC1(C)OB(c2ccc(N)c([N+](=O)[O-])c2)OC1(C)C
Reactant: Fc1cccc(C(F)(F)F)c1Br
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: CCOC(C)=O
Solvent: COCCOC
Product: Nc1ccc(-c2c(F)cccc2C(F)(F)F)cc1[N+](=O)[O-]
Temperature: 80 °C

Procedure:
A mixture of 2-nitro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (264 mg, 1.00 mmol, as prepared in Example 17, step A) and 2-bromo-1-fluoro-3-trifluoromethyl-benzene (243 mg, 1.00 mmol) in DME (5 mL) and 2 M aqueous Na2CO3 (4 mL, 8 mmol) was degassed via sonication, placed under argon and treated with Pd (PPh3)4 (115 mg, 0.100 mmol). The resulting mixture was heated at 80° C. for 16 h and allowed to cool to room temperature. The resulting mixture was diluted with EtOAc (10 mL) and washed twice with water (10 mL). The aqueous layer was extracted with additional EtOAc (10 mL), and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified on silica (EtOAc/hexanes, 0:100 to 50:50, v/v) to yield 6′-fluoro-3-nitro-2′-trifluoromethyl-biphenyl-4-yl-amine.
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:35]([N:37]3[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][C@@H:45]4[CH2:49][O:48]C(C)(C)[O:46]4)[CH2:39][CH2:38]3)=[O:36])[C@@:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)([CH3:27])[C@@:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([CH3:19])[N:18]=2)=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2]>O1CCCC1.FC(F)(F)C(O)=O>[C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:35]([N:37]3[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][C@@H:45]([OH:46])[CH2:49][OH:48])[CH2:39][CH2:38]3)=[O:36])[C:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)([CH3:27])[C:17]([C:20]3[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=3)([CH3:19])[N:18]=2)=[CH:7][N:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOc1nc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(CC[C@@H]2COC(C)(C)O2)CC1
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Product: CCOc1nc(C(C)(C)C)ncc1C1=NC(C)(c2ccc(Cl)cc2)C(C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(CC[C@@H](O)CO)CC1
Temperature: 25 °C
Reaction time: 48 h
Yield: 23.3 %

Procedure:
To a solution of rac-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazol-1-yl]-{4-[2-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-piperazin-1-yl}-methanone (30 mg) in tetrahydrofuran (1 mL) was added 10 drops of trifluoroacetic acid. The mixture was stirred at room temperature for 2 d and concentrated. Purification of the crude residue by reversed phase HPLC (C18-silica gel, eluting with water and acetonitrile) gave the title compound as white solids (6.6 mg). HR-MS (ES, m/z) calculated for C36H47N6O4Cl2 [(M+H)+] 697.3031, observed 697.3027.
Reaction SMILES: CS(C)=O.C[O-].[Na+].[C:8]([O:16]C)(=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:20])[CH3:19]>CO.COCCOCCOC>[C:21]1([C:18](=[O:20])[CH2:19][C:8]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:16])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC(=O)c1ccccc1
Reactant: COC(=O)c1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: COCCOCCOC
Solvent: CS(C)=O
Solvent: CO
Product: O=C(CC(=O)c1ccccc1)c1ccccc1
Temperature: 30 °C
Reaction time: 2 h

Procedure:
100 g of anhydrous dimethyl sulfoxide, 100 g of diethylene glycol dimethyl ether, 6 g of absolute methanol and 18 g of sodium methylate (97%) are charged to an apparatus as described in Example 1. A mixture of 45 g of methyl benzoate and 36 g of acetophenone are added dropwise to this mixture at 25 ° C. over 45 minutes. After this addition, the reaction mixture is stirred for 2 hours at 30° C. and the solvent is removed by vacuum distillation at a temperature of <60 ° C. The residue is diluted with 150 g of methyl tert-butyl ether, cooled to 0° C. and filtered. The filter cake is washed twice with methyl tert-butyl ether. The pale grey solid is thereafter taken up in dilute hydrochloric acid and stirred.
Reaction SMILES: C([O:3][C:4]([C@@H:6]1[CH2:10][C@@H:9]([S:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[Cl:21])(=[O:13])=[O:12])[CH2:8][C@H:7]1[CH2:22][O:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)=O)C.[NH2:33][C:34]1([C:37]#[N:38])[CH2:36][CH2:35]1>>[C:37]([C:34]1([NH:33][C:4]([C@@H:6]2[CH2:10][C@@H:9]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[Cl:21])(=[O:13])=[O:12])[CH2:8][C@H:7]2[CH2:22][O:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)=[O:3])[CH2:36][CH2:35]1)#[N:38]
Reactant: CCOC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccc(F)cc2Cl)C[C@H]1COCc1ccc(OC)cc1
Reactant: N#CC1(N)CC1
Product: COc1ccc(COC[C@@H]2C[C@H](S(=O)(=O)c3ccc(F)cc3Cl)C[C@H]2C(=O)NC2(C#N)CC2)cc1

Procedure:
The title compound was prepared in analogy to example 68 step 10 and 11 using (1R,2R,4S)-4-(2-chloro-4-fluoro-benzenesulfonyl)-2-(4-methoxy-benzyloxymethyl)-cyclopentanecarboxylic acid ethyl ester (example 153 step 8) and 1-amino-cyclopropanecarbonitrile. Light yellow oil (80%). MS (EI): 521.2 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([N:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[C:10]([O:12][C@@H:13]1[CH:18]2[CH2:19][CH2:20][N:15]([CH2:16][CH2:17]2)[CH2:14]1)=[O:11].[Cl:27][CH2:28][C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:30]>C(#N)C>[Cl-:27].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([N:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[C:10]([O:12][C@@H:13]1[CH:18]2[CH2:19][CH2:20][N+:15]([CH2:28][C:29](=[O:30])[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([CH2:16][CH2:17]2)[CH2:14]1)=[O:11]
Reactant: O=C(CCl)c1ccccc1
Reactant: O=C(O[C@H]1CN2CCC1CC2)C(c1ccc(F)cc1F)N1CCCCC1
Solvent: CC#N
Product: O=C(C[N+]12CCC(CC1)[C@@H](OC(=O)C(c1ccc(F)cc1F)N1CCCCC1)C2)c1ccccc1
Product: [Cl-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 67 %

Procedure:
(R)-quinuclidin-3-yl 2-(2,4-difluorophenyl)-2-(piperidin-1-yl)acetate (275 mg, 0.75 mmol) and 2-chloro-1-phenylethanone (128 mg, 0.83 mmol) were dissolved in acetonitrile (8 ml) and stirred at room temperature overnight. The solvent was evaporated and the residue was triturated with Et2O and sonicated. The resulting precipitate was recovered by suction filtration and washed on the filter-paper with EtOAc and Et2O to obtain the title compound (261 mg, 66.6% yield) as a white solid.
Reaction SMILES: [CH3:1][C:2]([NH:5][S:6]([C:9]1[C:17]2[CH2:16][S:15][C:14](=O)[C:13]=2[CH:12]=[CH:11][CH:10]=1)(=[O:8])=[O:7])([CH3:4])[CH3:3].B(F)(F)F.CCOCC>O1CCCC1>[CH3:4][C:2]([NH:5][S:6]([C:9]1[C:17]2[CH2:16][S:15][CH2:14][C:13]=2[CH:12]=[CH:11][CH:10]=1)(=[O:8])=[O:7])([CH3:1])[CH3:3]
Reactant: CC(C)(C)NS(=O)(=O)c1cccc2c1CSC2=O
Agent: FB(F)F
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)(C)NS(=O)(=O)c1cccc2c1CSC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 47.3 %

Procedure:
A suspension of 8.0 g of 1,3-dihydro-N-(1,1-dimethylethyl)-1-oxobenzo[c]thiophene-4-sulfonamide in a mixture of 15 ml of tetrahydrofuran, 25 ml of boron trifluoride etherate was cooled to 10° under N2, and 56 ml of a 1M solution of borane tetrahydrofuran complex was added dropwise at approximately 10°. The reaction mixture was allowed to warm to ambient temperature as a gas was evolved. When ambient temperature was reached, a slow exotherm to 31° occurred. When the exotherm subsided, the reaction mixture was heated to reflux for two hours, then cooled and allowed to stand overnight. The supernatant was decanted for some brown solid, and concentrated in vacuo. The resulting yellow oil was cooled to approximately 5°, acidified with 5% hydrochloric acid (gas evolution), and diluted with 150 ml water. The aqueous mixture was extracted with ethyl acetate. The organic solution was washed twice with water, dried over magnesium sulfate, then filtered and the filtrate concentrated in vacuo. The resulting yellow oil was purified by chromatography, using methylene chloride as eluent, to give 3.6 g of 1,3-dihydro-N-(1,1-dimethylethyl)benzo[c]thiophene-4-sulfonamide, m.p. 128.5°-132°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C1(C)C=CC=CC=1.C(N(CC)CC)C.ClC(Cl)(O[C:41](=[O:47])[O:42][C:43](Cl)(Cl)Cl)Cl.[Cl:49][C:50]1[CH:60]=[CH:59][C:53]([O:54][CH2:55][CH2:56]CO)=[CH:52][CH:51]=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:41](=[O:47])[O:42][CH2:43][CH2:56][CH2:55][O:54][C:53]2[CH:59]=[CH:60][C:50]([Cl:49])=[CH:51][CH:52]=2)=[CH:18][CH:17]=1
Reactant: OCCCOc1ccc(Cl)cc1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2nccc(Oc3ccc(NC(=O)OCCCOc4ccc(Cl)cc4)cc3)c2cc1OC
Temperature: 25 °C
Yield: 59 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (79 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-chlorophenoxy)-1-propanol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 55%).
Reaction SMILES: [CH3:1][C:2]([O:11][OH:12])([CH2:4][CH2:5][C:6]([CH3:10])([O:8][OH:9])[CH3:7])[CH3:3].CN([Si:16](N(C)C)([CH3:18])[CH3:17])C>CCOCC>[CH3:17][Si:16]1([CH3:18])[O:12][O:11][C:2]([CH3:1])([CH3:3])[CH2:4][CH2:5][C:6]([CH3:10])([CH3:7])[O:8][O:9]1
Reactant: CC(C)(CCC(C)(C)OO)OO
Reactant: CN(C)[Si](C)(C)N(C)C
Solvent: CCOCC
Product: CC1(C)CCC(C)(C)OO[Si](C)(C)OO1
Temperature: 16 °C
Reaction time: 1 h
Yield: 97.8 %

Procedure:
Into a 250 ml flask equipped with a magnetic stirring bar, addition funnel and calcium sulfate drying tube is placed a solution of 10.84g (0.06 mole, 98.66% pure) of 2,5-dimethyl-2,5-dihydroperoxyhexane in 120 ml of anhydrous ether. The solution is cooled to 16° C. and a solution of 8.77g (0.06 mole) of bis(dimethylamino) dimethylsilane in 30 ml of anhydrous ether is added slowly dropwise. The reaction temperature is maintained between 15° and 20° by use of an ice bath and by adjusting the rate of addition. After the addition is complete, the solution is stirred at room temperature for one hour. The solution is filtered to remove a small amount of suspended solid. The solvent is removed by distillation yielding 13.75g of 3,3,6,6,9,9-hexamethyl-1,2,4,5-tetraoxa-3-silacyclononane (theoretical yield 14.05g, 97.9%; A.O. analysis 13.32%, theoretical 13.67%, 97.4% pure). The infrared spectrum of the reaction product of this example is identical to the spectrum of material produced in Example 1.
Reaction SMILES: Cl.[CH3:2][O:3][NH:4][CH3:5].[CH:6]1([S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH2:22][CH:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:19](O)=[O:20])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH2:8][CH2:7]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[CH:6]1([S:9]([C:12]2[CH:13]=[CH:14][C:15]([CH:18]([CH2:22][CH:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[C:19]([N:4]([O:3][CH3:2])[CH3:5])=[O:20])=[CH:16][CH:17]=2)(=[O:10])=[O:11])[CH2:8][CH2:7]1
Reactant: O=C(O)C(CC1CCOCC1)c1ccc(S(=O)(=O)C2CC2)cc1
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CON(C)C(=O)C(CC1CCOCC1)c1ccc(S(=O)(=O)C2CC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.6 %

Procedure:
To a solution of N-methoxymethanamine hydrochloride (3.90 g) in N,N-dimethylformamide (100 mL) was added triethylamine (5.60 mL) for neutralization, and a solution of 2-[4-(cyclopropylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (11.23 g) in N,N-dimethylformamide (50 mL), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (9.60 g) and 1-hydroxybenzotriazole (6.80 g) were added under ice-cooling. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate, and washed with water, 1N aqueous hydrochloric acid solution and saturated aqueous sodium hydrogen carbonate. The ethyl acetate layer was dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (10.2 g, yield 81%) was obtained as colorless amorphous crystals from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). MS: 382 (MH+).
Reaction SMILES: CC([O-])(C)C.[K+].C1COCC1.[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][C:20]=2[CH2:22][C:23]([NH2:25])=[O:24])[CH:15]=[CH:14]1.CO[C:28](=[O:49])[C:29]([C:31]1[C:39]2[C:34](=[C:35]([CH2:40][NH:41][C:42]([O:44]C(C)(C)C)=O)[CH:36]=[CH:37][CH:38]=2)[NH:33][CH:32]=1)=O.[CH3:50][N:51](C=O)[CH3:52]>>[CH3:50][N:51]([CH3:52])[C:42]([NH:41][CH2:40][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:34]=1[NH:33][CH:32]=[C:31]2[C:29]1[C:28](=[O:49])[NH:25][C:23](=[O:24])[C:22]=1[C:20]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:21]=1[N:13]([CH3:12])[CH:14]=[CH:15]2)=[O:44]
Reactant: CN(C)C=O
Reactant: COC(=O)C(=O)c1c[nH]c2c(CNC(=O)OC(C)(C)C)cccc12
Reactant: Cn1ccc2cccc(CC(N)=O)c21
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CN(C)C(=O)NCc1cccc2c(C3=C(c4cccc5ccn(C)c45)C(=O)NC3=O)c[nH]c12
Temperature: 140 °C
Yield: 14 %

Procedure:
A 1.0 M solution of KOtBu in THF (4.77 ml, 4.77 mmol) was added to a solution of 2-(1-methyl-1H-indol-7-yl-acetamide (0.3 g, 1.59 mmol) and [7-(tert-Butoxycarbonylamino-methyl)-1H-indol-3-yl]-oxo-acetic acid methyl ester (0.53 g, 1.59 mmol) in DMF (15 ml) at room temperature. The reaction was heated at 140° C. for 4 h, allowed to cool to room temperature quenched with pH 7 buffer. The mixture was poured into EtOAc, extracted, washed with saturated aq NaHCO3, brine, dried (MgSO4), filtered, and concentrated onto SiO2. Flash chromatography (50:50 ethyl acetate: hexanes) afforded the title compound (0.1 g, 14%) as an orange solid. MS (electrospray, m/z) 442.2 (M++1), 440.3 (M−−1).