Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O)=[CH:16][CH:15]=[CH:14][C:13]=2[C:27]([F:30])([F:29])[F:28])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:31][C:32]1[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=1[NH2:34]>>[CH3:31][C:32]1[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=1[NH:34][CH2:22][C:21]1[CH:20]=[C:19]([C:18]2[C:17]3[C:12](=[C:13]([C:27]([F:29])([F:30])[F:28])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:8])[CH:26]=[CH:25][CH:24]=1
Reactant: Cc1ccccc1N
Reactant: O=Cc1cccc(-c2c(C(=O)c3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Product: Cc1ccccc1NCc1cccc(-c2c(C(=O)c3ccccc3)cnc3c(C(F)(F)F)cccc23)c1

Procedure:
The title compound was prepared from 3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]benzaldehyde and 2-methylaniline according to the procedure of Example 66. MS (ES) m/z 497.3.
Reaction SMILES: [OH:1][C:2]1[CH:13]=[CH:12][C:5]2[CH2:6][C:7](=[O:11])[NH:8][CH2:9][CH2:10][C:4]=2[CH:3]=1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18]Br.C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18][O:1][C:2]1[CH:13]=[CH:12][C:5]2[CH2:6][C:7](=[O:11])[NH:8][CH2:9][CH2:10][C:4]=2[CH:3]=1
Reactant: O=C1Cc2ccc(O)cc2CCN1
Reactant: Clc1cccc(CBr)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: O=C1Cc2ccc(OCc3cccc(Cl)c3)cc2CCN1

Procedure:
In an analogous manner to that described in Example 17 c), the alkylation of 7-hydroxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one [Example 19 b)] by 3-chlorobenzylbromide in the presence of potassium carbonate in 2-butanone yielded the 7-(3-chloro-benzyloxy)-1,3,4,5-tetrahydro-benzo[d]azepin-2-one as a white solid; MS: m/e=302 (M+H)+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[C:10]([CH2:16][CH3:17])([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:18]1([NH2:21])[CH2:20][CH2:19]1.C([BH3-])#N.[Na+]>CO>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:21][CH:18]2[CH2:20][CH2:19]2)[C:10]([CH2:16][CH3:17])([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCC1(C)CN(Cc2ccccc2)CCC1=O
Reactant: NC1CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CCC1(C)CN(Cc2ccccc2)CCC1NC1CC1
Reaction time: 6 h

Procedure:
1-Benzyl-3-ethyl-3-methyl-4-piperidinone (4.2 g, 18.18 mmol) was added to the stirred solution cyclopropylamine (6.5 g, 115 mmol) in methanol (100 ml) and stirred for 6 hr. Sodium cyanoborohydride (1.14 g, 18.18 mmol) was added to it and reaction mixture was stirred for 15 hr. The reaction mixture was concentrated to dryness, triturated with water, extracted with chloroform, dried (Na2SO4) and concentrated to furnish crude 1-benzyl-4-cyclopropylamino-3-ethyl-3-methylpiperidine. Yield 4 g (88%), C18H28N2, m/z 273 (M+1).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([C:9]2[O:10][CH:11]=[CH:12][CH:13]=2)[N:3]=1.[Br:14]N1C(=O)CCC1=O>CN(C=O)C.CCOC(C)=O>[Br:14][C:11]1[O:10][C:9]([C:4]2[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([Cl:1])[N:3]=2)=[CH:13][CH:12]=1
Reactant: Clc1cc(-c2ccco2)nc(Cl)n1
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Clc1cc(-c2ccc(Br)o2)nc(Cl)n1
Yield: 65.4 %

Procedure:
To a stirred solution of 2,4-Dichloro-6-furan-2-yl-pyrimidine (1.44 g, 6.71 mmol) in DMF (20 ml) was added N-bromosuccinimide (1.31 g, 7.38 mmol) in a portionwise fashion. The resultant mixture was stirred at room temperature for a 2.5 hours before being diluted in EtOAc (50 ml) and washed with water (2×50 ml). The organic extract was dried (MgSO4), filtered and concentrated in vacuo to give an orange, semi-crystalline slurry. The crude residue was washed with ether and filtered to leave the desired product (1.29 g, 99%) as a whited crystalline solid in suitably clean form to be used without any further purification. m/z (LC-MSW, ESP):294 [M+H]+, R/T=5.09 mins.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:14][N:15]1[C:23]2[C:18](=[CH:19][C:20]([C:24]([OH:33])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])=[CH:21][CH:22]=2)[CH:17]=[C:16]1[CH3:34].[CH3:35][N:36]([CH3:40])[C:37](Cl)=[O:38].CCOCC.Cl>N1C=CC=CC=1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([O:13][C:37](=[O:38])[N:36]([CH3:40])[CH3:35])=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:14][N:15]1[C:23]2[C:18](=[CH:19][C:20]([C:24]([OH:33])([C:25]([F:26])([F:27])[F:28])[C:29]([F:32])([F:31])[F:30])=[CH:21][CH:22]=2)[CH:17]=[C:16]1[CH3:34]
Reactant: CN(C)C(=O)Cl
Reactant: Cc1oc(-c2ccc(O)cc2)nc1Cn1c(C)cc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
Agent: Cl
Solvent: CCOCC
Solvent: c1ccncc1
Product: Cc1oc(-c2ccc(OC(=O)N(C)C)cc2)nc1Cn1c(C)cc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
Temperature: 60 °C
Reaction time: 2 h
Yield: 65.8 %

Procedure:
A solution of 25 mg (0.052 mmol) 4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol (example 99) in 1 mL of pyridine was treated with 28 mg (0.26 mmol) of dimethyl carbamoylchloride and stirred at 60° C. for 2 hours. Et2O and aqueous HCl were added and the phases separated. The aqueous phase was extracted with Et2O and the combined organic phases dried over Na2SO4. Evaporation of the solvent and column chromatography on silica gel with n-heptane/EtOAc 1:1 yielded 19 mg (66%) of dimethyl-carbamic acid 4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenyl ester, light yellow solid, MS: 556 (MH+).
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[CH:5]=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18].[CH2:20]([NH2:24])[CH2:21][CH2:22][CH3:23]>C1COCC1>[CH2:20]([NH:24][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[CH:5]=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18])[CH2:21][CH2:22][CH3:23]
Reactant: CCN(CC)CCCOc1ccc([N+](=O)[O-])c(F)c1
Reactant: CCCCN
Solvent: C1CCOC1
Product: CCCCNc1cc(OCCCN(CC)CC)ccc1[N+](=O)[O-]

Procedure:
A solution of 2-fluoro-4-(3-diethylamino-1-propoxy)nitrobenzene (2 mmol; preparation described in Example 5) in THF (5 mL) is treated with n-butylamine (2.4 eq) at rt. After completion of the reaction, the reaction mixture is concentrated in vacuo. The residue is redissolved in EtOAc (10 mL), washed with saturated sodium bicarbonate solution, water, and brine. The organic phase is then dried over sodium sulfate and the solvent is removed in vacuo to afford the product, 2-n-butylamino-4-(3-diethylamino-1-propoxy)nitrobenzene (580 mg) which was used for further transformation without further purification.
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])[C:9]([C:11]1[CH:31]=[CH:30][C:14]2[N:15]([CH3:29])[C:16]([CH2:18][NH:19][C:20]3[CH:25]=[CH:24][C:23]([C:26](=[NH:28])[NH2:27])=[CH:22][CH:21]=3)=[N:17][C:13]=2[CH:12]=1)=[O:10].Cl[C:39]([O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])=[O:40]>ClCCl.CO>[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])[C:9]([C:11]1[CH:31]=[CH:30][C:14]2[N:15]([CH3:29])[C:16]([CH2:18][NH:19][C:20]3[CH:25]=[CH:24][C:23]([C:26](=[NH:27])[NH:28][C:39]([O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])=[O:40])=[CH:22][CH:21]=3)=[N:17][C:13]=2[CH:12]=1)=[O:10]
Reactant: CCCCCCOC(=O)Cl
Reactant: COC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C)c1ccccn1
Agent: Cl
Solvent: CO
Solvent: ClCCl
Product: CCCCCCOC(=O)NC(=N)c1ccc(NCc2nc3cc(C(=O)N(CCC(=O)OC)c4ccccn4)ccc3n2C)cc1
Yield: 51 %

Procedure:
Prepared analogously to Example 90 from 1-methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-methoxycarbonylethyl)-amide-hydrochloride and n-hexyl chloroformate. Yield: 51% of theory, C33H39N7O5 (613.7) Rf value: 0.56 (silica gel; dichloromethane/methanol=9:1) ##EQU76##
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([OH:27])=[O:26])=[CH:21][CH:20]=1>CN(C=O)C>[C:25]([C:22]1[CH:23]=[CH:24][C:19]([CH2:18][S:1][C:2]2[NH:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)=[CH:20][CH:21]=1)([OH:27])=[O:26]
Reactant: O=C(O)c1ccc(CBr)cc1
Reactant: Sc1nc2ccccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(O)c1ccc(CSc2nc3ccccc3[nH]2)cc1
Reaction time: 4 h

Procedure:
4.6 g (30 mmol) of 2-mercaptobenzimidazole were initially introduced into 60 ml of dry DMF, 8.3 g (60 mmol) of K2CO3 were added, and a solution of 6.7 g (31 mmol) of α-bromo-4-toluic acid in 15 ml of dry DMF was added dropwise at room temperature. After 4 hours, a solid residue was filtered off with suction, the DMF was removed in vacuo, and the residue was taken up in aqueous hydrochloric acid at pH 2. Crystals of the title compound separated out, and these were washed with water, methanol and ether and dried.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]1[C:28]2[CH:29]=[CH:30][C:31]([CH:33]=O)=[CH:32][C:27]=2[O:26][CH:25]=[CH:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(Cl)(Cl)Cl>[O:23]1[C:28]2[CH:29]=[CH:30][C:31]([CH2:33][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=5)[N:13]=[CH:12][C:11]4=[O:22])[CH2:6][CH2:7]3)=[CH:32][C:27]=2[O:26][CH:25]=[CH:24]1
Reactant: COc1ccc2ncc(=O)n(CCN3CCC(N)CC3)c2c1
Reactant: O=Cc1ccc2c(c1)OC=CO2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: COc1ccc2ncc(=O)n(CCN3CCC(NCc4ccc5c(c4)OC=CO5)CC3)c2c1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 10.6 %

Procedure:
To 15 mL of a chloroform solution containing 141 mg of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one and 68 mg of 1,4-benzodioxine-6-carbaldehyde, 28 mg of acetic acid was added and stirred at room temperature for 4.5 hours. To the reaction mixture, 148 mg of sodium triacetoxyborohydride was added and stirred for 1 hour. Aqueous saturated sodium hydrogen carbonate solution was added and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60, eluent; chloroform:methanol=10:1], to give 20 mg of 1-(2-(4-((1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one as a brown oil.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]#[N:5].C(N(CC)CC)C.FC(F)(F)S(O[Si:19]([CH3:22])([CH3:21])[CH3:20])(=O)=O>C1(C)C=CC=CC=1>[CH3:20][Si:19]([N:5]([Si:19]([CH3:22])([CH3:21])[CH3:20])[CH2:4][CH2:3][C:2]#[N:1])([CH3:22])[CH3:21]
Reactant: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: N#CCCN
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: C[Si](C)(C)N(CCC#N)[Si](C)(C)C
Temperature: 25 °C
Reaction time: 48 h
Yield: 89.9 %

Procedure:
About 5.04 g of 3-aminopropionitrile, 16.01 g of triethylamine, and 10 ml of toluene were mixed in a round-bottom reaction flask cooled with an ice bath. To this mixture was added, in a dropwise fashion, a solution of 35.16 g of trimethylsilyl trifluoromethanesulfonate in 50 ml of toluene. The resulting mixture was stirred at room temperature for 2 days to give a biphasic mixture. The top layer was transferred to another flask, and the bottom layer was extracted with 50 ml of toluene. The combined toluene solution was evaporated under vacuum. The residue was extracted with 100 ml of hexane, and the hexane layer was evaporated under vacuum, yielding 3-[bis(trimethylsilyl)amino]propionitrile (3-BTMSAPN) as a white solid (13.86 g, 90% yield). The 1H NMR data (C6D6, 25° C., referenced to tetramethylsilane) of the product are listed as follows: δ 2.65 (triplet, 2H, CH2 protons), 1.59 (triplet, 2H, CH2 protons), −0.05 (singlet, 18H, Si—CH3 protons). From the 1H NMR data, the structure of the product was determined to be as follows:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([OH:25])=[O:24])=[CH:19][CH:18]=2)([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][Si](C=[N+]=[N-])(C)C.CCCCCC>CO>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:25][CH3:26])=[O:24])=[CH:19][CH:18]=2)([OH:14])[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc(OCC2(O)CCN(Cc3ccccc3)CC2)cc1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: CCCCCC
Product: COC(=O)c1ccc(OCC2(O)CCN(Cc3ccccc3)CC2)cc1

Procedure:
The compound (0.86 g) obtained in Step 4 was dissolved in methanol (10 mL) and to the solution was added a 2M trimethylsilyidiazomethan-hexane solution (1.3 mL). After completion of the reaction, the residue from which the solvent was removed under reduced pressure was purified by silica gel column chromatography (Chromatorex NH™) (eluent; ethyl acetate:hexane=1:19 to 1:9) to obtain the titled compound (0.8 g) as crystals.
Reaction SMILES: [H-].[Na+].C[O:4][C:5](=[O:17])[CH2:6][C:7]1[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8]=1[CH3:16].[C:18]([C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][C:21]=1[O:30][CH2:31][CH3:32])#[N:19]>C1COCC1.C1COCC1.CN(C=O)C>[C:18]([C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:9]2[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:15]3[C:7]([CH2:6][C:5]([OH:4])=[O:17])=[C:8]2[CH3:16])(=[O:28])=[O:27])=[CH:22][C:21]=1[O:30][CH2:31][CH3:32])#[N:19]
Reactant: COC(=O)Cc1c(C)[nH]c2ncccc12
Reactant: CCOc1cc(S(=O)(=O)Cl)ccc1C#N
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCOc1cc(S(=O)(=O)n2c(C)c(CC(=O)O)c3cccnc32)ccc1C#N
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a stirred, ice-cooled (0° C.) suspension of sodium hydride (26.3 mg of a 60% dispersion in mineral oil, 0.686 mmol) in dry THF (10 ml) under an inert atmosphere of Argon is added dropwise (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((0.1 g, 0.49 mmol) in THF/DMF (4 ml of a 3:1 mixture). The reaction mixture is stirred at 0° C. for 1 hour and then treated with 4-cyano-3-ethoxy-benzenesulfonyl chloride (168 mg, 0.686 mmol) in dry THF (1 ml). Stirring continued at 0° C. for 10 minutes and at room temperature for 10 minutes and then the reaction mixture is poured onto water (50 ml). The mixture is extracted with ethyl acetate (2×50 ml) and the organic portions are combined, washed brine (50 ml), dried (MgSO4) and concentrated in vacuo. The resulting crude is purified by chromatography on silica eluting with iso-hexane/ethyl acetate (0%-20% ethyl acetate) to yield the titled product. (MH+ 414).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:20]=1[CH:21]=O>>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:21]([C:12]1[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:10]=2)[NH:14][CH:13]=1)[C:20]1[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:19]=1[Cl:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(COc2ccc3[nH]ccc3c2)cc1
Reactant: O=Cc1ccc(Cl)cc1Cl
Product: Clc1ccc(C(c2c[nH]c3ccc(OCc4ccccc4)cc23)c2c[nH]c3ccc(OCc4ccccc4)cc23)c(Cl)c1

Procedure:
The compound Bis(5-benzyloxyindol-3-yl)-(2,4-dichlorophenyl)methane was prepared following procedure A, starting from 5-benzyloxy indole and 2,4 dichloro benzaldehyde. LC: Tr 2.89 min, MS: 603 (M+H)+
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].N1C=CN=C1.O>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Oc1ccc(OCc2ccccc2)cc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)Oc1ccc(OCc2ccccc2)cc1
Reaction time: 8 h

Procedure:
4-Benzyloxyphenol (39 g, 0.19 mole) and tert-butyldimethylsilyl chloride (32.31 g, 0.21 mole) were dissolved in dimethylformamide (200 ml). Imidazole (14.59 g, 0.21 mole) was added in portions and after the addition the reaction mixture was stirred overnight. Water was added and the mixture was extracted with ether. The combined organic layers were washed with water and dried over anhydrous calcium chloride. The solvent was evaporated to yield crystallized product (60.2 g, 0.19 mole, 98%).
Reaction SMILES: O=[C:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1.[CH3:14][C:15]1[CH:16]=[C:17]([Mg]Br)[CH:18]=[C:19]([CH3:21])[CH:20]=1>>[CH3:14][C:15]1[CH:16]=[C:17]([CH:2]2[C:9]3[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=3[CH2:4][CH2:3]2)[CH:18]=[C:19]([CH3:21])[CH:20]=1
Reactant: COC(=O)c1cc2c([nH]1)CCC2=O
Reactant: Cc1cc(C)cc([Mg]Br)c1
Product: COC(=O)c1cc2c([nH]1)CCC2c1cc(C)cc(C)c1

Procedure:
The title compound was synthesized in two steps. First, methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.5 g, 2.79 mmol) and 3,5-dimethylphenylmagnesium bromide (14 mL, 6.97 mmol, 0.5 M in THF, 2.5 equiv) were reacted according to General Procedure 3 to give the endo olefin-containing compound methyl 4-(3,5-dimethylphenyl)-1,6-dihydrocyclopenta[b]pyrrole-2-carboxylate, which was then hydrogenated according to General Procedure 6 (with 5% Pd/C), and was purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-100% EtOAc/heptane to afford the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.20-2.36 (m, 7H), 2.71-2.98 (m, 3H), 3.83-3.86 (m, 3H), 4.17 (t, J=7.35 Hz, 1H), 6.49 (s, 1H), 6.67 (d, J=1.42 Hz, 1H), 6.82-6.88 (m, 2H), 9.02 (br. s, 1H).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.P([O-])(O)(O)=[O:13].[K+].N(S([O-])(=O)=O)(S([O-])(=O)=O)[O].[K+].[K+]>CO.O>[N:7]1[C:8]2[C:9](=[O:13])[CH:10]=[CH:11][C:2](=[O:1])[C:3]=2[CH:4]=[CH:5][CH:6]=1
Reactant: Oc1cccc2ncccc12
Reactant: O=P([O-])(O)O
Agent: [K+]
Agent: [O]N(S(=O)(=O)[O-])S(=O)(=O)[O-]
Solvent: O
Solvent: CO
Product: O=C1C=CC(=O)c2ncccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 47.2 %

Procedure:
To a solution of 23.2 g of 5-hydroxyquinoline in 1600 ml of methanol in an ice bath was added a total of 36 g of potassium dihydrogen phosphate and 96 g of potassium nitroso disulfonate in 8.8 liters of water in five portions over a 1 hour period. The mixture was then stirred overnight at room temperature, followed by extraction with four 1500 ml portions of chloroform. The extracts were combined, dried, filtered through alumina and evaporated to dryness, giving 12.0 g of crude product. An analytical sample was prepared by crystallization from petroleum ether, mp 110° C.
Reaction SMILES: [S-2:1].[Na+].[Na+].CO.[C:6]([N:10]=[N:11][C:12]1(Cl)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:9])([CH3:8])[CH3:7]>O>[C:6]([N:10]=[N:11][C:12]1([S:1][C:12]2([N:11]=[N:10][C:6]([CH3:9])([CH3:8])[CH3:7])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:9])([CH3:8])[CH3:7]
Reactant: [S-2]
Reactant: CC(C)(C)N=NC1(Cl)CCCCC1
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC(C)(C)N=NC1(SC2(N=NC(C)(C)C)CCCCC2)CCCCC1
Temperature: 15 °C
Reaction time: 0.75 h
Yield: 30 %

Procedure:
A solution of 1.56 grams (.02 moles) of sodium sulfide in 50 ml. of 75% aqueous methanol was prepared in a 200 ml. beaker and cooled to 15°C. To this solution was added 8.2 grams (.0404 moles) of 1-t-butylazo-1-chlorocyclohexane dropwise over a 15 minute period. After the addition was complete, the reaction was stirred for 45 minutes at room temperature and poured into 100 ml. of cold water. A solid formed and was filtered off and dried. The dried material weighed 2.2 grams (30% yield). The infrared spectrum of the product was in agreement with the structure of the desired compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][OH:8].[Cl:9][C:10]1[S:14][C:13]([S:15]([NH:18][C:19]2[C:24](Cl)=[N:23][CH:22]=[CH:21][N:20]=2)(=[O:17])=[O:16])=[CH:12][CH:11]=1>>[Cl:9][C:10]1[S:14][C:13]([S:15]([NH:18][C:19]2[C:24]([O:8][CH2:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[N:23][CH:22]=[CH:21][N:20]=2)(=[O:16])=[O:17])=[CH:12][CH:11]=1
Reactant: OCc1ccccn1
Reactant: O=S(=O)(Nc1nccnc1Cl)c1ccc(Cl)s1
Product: O=S(=O)(Nc1nccnc1OCc1ccccn1)c1ccc(Cl)s1
Temperature: 70 °C

Procedure:
Prepared by the method of Example 20b using pyridine-2-methanol and 5-chloro-N-(3-chloro-2-pyrazinyl)-2-thiophenesulphonamide with reaction mixture heated at 70° C. for 4 h.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH2:14][OH:15])=[CH:4][CH:3]=1.[CH2:16]([O:18][C:19]([C:21]1([C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][CH:25]=2)[CH2:23][CH2:22]1)=[O:20])[CH3:17]>>[CH2:16]([O:18][C:19]([C:21]1([C:24]2[CH:29]=[CH:28][C:27]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[CH2:14][OH:15])=[CH:4][CH:3]=3)=[CH:26][CH:25]=2)[CH2:22][CH2:23]1)=[O:20])[CH3:17]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1CO
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CO)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 3, Step 5, using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-methanol and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[C:21]3[C:16](=[C:17]([CH2:22][S:23][CH3:24])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH2:9][CH2:10][C:11]#[N:12])=[C:4]([F:25])[CH:3]=1.ClCCl.ClC1C=CC=C(C(OO)=[O:37])C=1>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[C:21]3[C:16](=[C:17]([CH2:22][S:23]([CH3:24])=[O:37])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH2:9][CH2:10][C:11]#[N:12])=[C:4]([F:25])[CH:3]=1
Reactant: CSCc1cccc2c(C(CCC#N)c3ccc(Cl)cc3F)c[nH]c12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CO
Solvent: ClCCl
Product: CS(=O)Cc1cccc2c(C(CCC#N)c3ccc(Cl)cc3F)c[nH]c12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
200 mg (0.54 mmol) of the compound from Example 38 were introduced into 30 ml of dichloromethane at 0° C., 132 mg (0.54 mmol) of 70% pure meta-chloroperbenzoic acid were added, and the mixture was stirred at RT overnight. 2 ml of methanol were added, and the residue after concentration was taken up in dichloromethane, washed twice with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, and the organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 107 mg (51% of theory) of the title compound as mixture of diastereomers.