Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH:20]=O)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29].[NH2:30][CH2:31][CH2:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][NH:30][CH2:31][CH2:32][C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29]
Reactant: NCCc1cccnc1
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(Cl)c3c2C(=O)NC3)cc2cc(C=O)ccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)n1c(-c2ccc(Cl)c3c2C(=O)NC3)cc2cc(CNCCc3cccnc3)ccc21

Procedure:
In a similar manner to Step 1 of Example 56, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (20.0 mg, 0.0487 mmol) was dissolved in dichloromethane (0.5 mL) and the solution was treated with 3-(2-aminoethyl)pyridine (0.012 mL, 0.10 mmol) and sodium triacetoxyborohydride (32 mg, 0.15 mmol) to obtain 4-chloro-7-{1-(tert-butoxycarbonyl)-5-[(2-(pyridin-3-yl)ethyl)aminomethyl]indol-2-yl}isoindolinone.
Reaction SMILES: Br[CH:2]1[CH2:7][CH2:6][O:5][C:3]1=[O:4].[C:8]([OH:13])(=[O:12])[C:9]([CH3:11])=[CH2:10].C(C(C)=O)C(C)C>C(N(CC)CC)C>[C:8]([O:13][CH:2]1[CH2:7][CH2:6][O:5][C:3]1=[O:4])(=[O:12])[C:9]([CH3:11])=[CH2:10]
Reactant: C=C(C)C(=O)O
Reactant: O=C1OCCC1Br
Solvent: CC(=O)CC(C)C
Solvent: CCN(CC)CC
Product: C=C(C)C(=O)OC1CCOC1=O
Temperature: 25 °C
Reaction time: 10 h

Procedure:
After charging 100 parts of α-bromo-γ-butyrolactone and 104.4 parts of methacrylic acid (2.0 times in mole based on α-bromo-γ-butyrolactone), a three times amount of methyl isobutyl ketone based on α-bromo-γ-butyrolactone was added thereto to form a solution. To this solution was added dropwise 153.6 parts of triethylamine (3.0 times in mole based on α-bromo-γ-butyrolactone). Then, the solution was stirred at room temperature for about 10 hours. After filtration, the organic layer was washed with 5% aqueous sodium hydrogen carbonate solution and then washed twice with water. The organic layer was concentrated to give α-methacryloyloxy-γ-butyrolactone represented by the following formula:
Reaction SMILES: [SH:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[NH2:7][CH2:8][CH2:9][CH2:10]O.[BrH:12]>>[BrH:12].[BrH:12].[NH2:7][CH2:8][CH2:9][CH2:10][S:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1
Reactant: NCCCO
Reactant: Sc1ncc[nH]1
Agent: Br
Product: NCCCSc1ncc[nH]1

Procedure:
A solution of 2-mercaptoimidazole (2 g.) and 3-aminopropanol (1.14 ml.) in hydrobromic acid (48%, 25 ml.) was heated under reflux for 25 hours. The reaction mixture was evaporated to dryness and the oily residual solid recrystallized twice from ethanol/ether to give 2-(3-aminopropylthio)imidazole dihydrobromide (3.55 g.), m.p. 160°-162°.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[NH2:11])[C:5]([OH:7])=[O:6].[C:12](=S)=[S:13].C(N(CC)CC)C>O1CCOCC1>[SH:13][C:12]1[NH:1][C:2]2[CH:3]=[C:4]([C:5]([OH:7])=[O:6])[CH:8]=[CH:9][C:10]=2[N:11]=1
Reactant: Nc1ccc(C(=O)O)cc1N
Reactant: S=C=S
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: O=C(O)c1ccc2nc(S)[nH]c2c1
Temperature: 25 °C
Yield: 36.1 %

Procedure:
30.4 g of 3,4-diaminobenzoic acid, 50 g of carbon disulfide and 50 g of triethylamine were dissolved in 200 ml of dioxane and the solution was refluxed by heating for 5 hours. The reaction mixture was cooled to room temperature, the crystals thus deposited were collected by filtration and recrystallized from water to obtain 14 g of 2-mercapto-5-carboxybenzimidazole. Melting Point: above 250° C.
Reaction SMILES: Cl.[C:2]([C:4]1([NH:7][C:8]([C@@H:10]2[CH2:14][C@@H:13]([S:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])(=[O:17])=[O:16])[CH2:12][NH:11]2)=[O:9])[CH2:6][CH2:5]1)#[N:3].[CH:28](OC1C=CC([N+]([O-])=O)=CC=1)=[O:29]>>[C:2]([C:4]1([NH:7][C:8]([C@@H:10]2[CH2:14][C@@H:13]([S:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:25])[F:26])(=[O:17])=[O:16])[CH2:12][N:11]2[CH:28]=[O:29])=[O:9])[CH2:5][CH2:6]1)#[N:3]
Reactant: N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3C(F)(F)F)CN2)CC1
Reactant: O=COc1ccc([N+](=O)[O-])cc1
Agent: Cl
Product: N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3C(F)(F)F)CN2C=O)CC1

Procedure:
(2S,4R)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide hydrochloride from experiment K5 was coupled with p-nitrophenyl formate in analogy to experiment L27 to give (2S,4R)-1-formyl-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide as a colorless oil. MS: 416.2 [M+H]+.
Reaction SMILES: C[O:2][C:3](=O)[N:4]=[C:5](SC)[C:6]([C:20]1[CH:21]=[C:22]([O:30][CH2:31][CH3:32])[C:23]2[O:28][CH2:27][O:26][CH2:25][C:24]=2[CH:29]=1)=[N:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([CH3:19])[O:16][N:15]=2)=[CH:10][CH:9]=1.[NH:36]([C:38]1[N:43]=[CH:42][CH:41]=[CH:40][N:39]=1)[NH2:37].C(N(CC)CC)C>CN(C=O)C>[CH2:31]([O:30][C:22]1[C:23]2[O:28][CH2:27][O:26][CH2:25][C:24]=2[CH:29]=[C:20]([CH:6]([NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]3[N:18]=[C:17]([CH3:19])[O:16][N:15]=3)=[CH:12][CH:13]=2)[C:5]2[NH:4][C:3](=[O:2])[N:36]([C:38]3[N:43]=[CH:42][CH:41]=[CH:40][N:39]=3)[N:37]=2)[CH:21]=1)[CH3:32]
Reactant: NNc1ncccn1
Reactant: CCOc1cc(C(=Nc2ccc(-c3noc(C)n3)cc2)C(=NC(=O)OC)SC)cc2c1OCOC2
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOc1cc(C(Nc2ccc(-c3noc(C)n3)cc2)c2nn(-c3ncccn3)c(=O)[nH]2)cc2c1OCOC2
Temperature: 85 °C
Reaction time: 8 h
Yield: 45.9 %

Procedure:
To a solution of 105 mg of {2-(8-ethoxy-4H-benzo[1,3]dioxin-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester in 2 ml of DMF there were added 20.9 mg of 2-hydrazinopyrimidine and 50 μl of triethylamine, and the mixture was stirred overnight at 85° C. under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 3 ml of methanol and 0.3 ml of acetic acid. After adding 100 mg of sodium cyanotrihydroborate to the solution, the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give 5-{(8-ethoxy-4H-benzo[1,3]dioxin-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-one (46 mg).
Reaction SMILES: [C:1]1(C2CC(=O)NC3C=CC=CC=3S2)C=CC=C[CH:2]=1.[ClH:19].[CH3:20][N:21]([CH3:45])[CH2:22][CH2:23][N:24]([CH3:44])[C:25]([N:27]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2S[CH:30]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:29][CH2:28]1)=[O:26]>>[ClH:19].[CH3:20][N:21]([CH3:45])[CH2:22][CH2:23][N:24]([CH3:44])[C:25]([N:27]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[CH2:2][CH2:1][CH:30]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:29][CH2:28]1)=[O:26]
Reactant: CN(C)CCN(C)C(=O)N1CCC(c2ccccc2)Sc2ccccc21
Reactant: O=C1CC(c2ccccc2)Sc2ccccc2N1
Agent: Cl
Product: CN(C)CCN(C)C(=O)N1CCC(c2ccccc2)CCc2ccccc21

Procedure:
By substituting an equivalent amount of 3,4,5,6-tetrahydro-4-phenyl-1-benzazocin-2(H)-one, m.p. 188°-189° (prepared as described in Example 1 of U.S. patent application, Ser. No. 418,910, filed Dec. 16, 1964), for the 2,3-dihydro-2-phenyl-1,5-benzothiazepin-4-one in part (A) of Example 1 and carrying out the precedure of the Example, there is obtained N-(2-dimethylaminoethyl)-1,2,3,4,5,6-hexahydro-N-methyl-4-phenyl-benzazocine-1carboxamide hydrochloride.
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[N:7]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1I)[CH2:8][C:9]1[O:10][CH:11]=[CH:12][N:13]=1)([CH3:4])([CH3:3])[CH3:2].[F:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[C:25]([O:32][CH3:33])[CH:24]=1>CCCCCCC.CCOC(C)=O>[C:1]([O:5][C:6](=[O:21])[N:7]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[C:26]1[CH:27]=[CH:28][C:23]([F:22])=[CH:24][C:25]=1[O:32][CH3:33])[CH2:8][C:9]1[O:10][CH:11]=[CH:12][N:13]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1cc(F)ccc1B(O)O
Reactant: CC(C)(C)OC(=O)N(Cc1ncco1)c1cnccc1I
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: COc1cc(F)ccc1-c1ccncc1N(Cc1ncco1)C(=O)OC(C)(C)C

Procedure:
The title compound was prepared in analogy to example 72, from (4-iodo-pyridin-3-yl)-oxazol-2-ylmethyl-carbamic acid tert-butyl ester and 4-fluoro-2-methoxyphenyl-boronic acid (CAS RN 179899-07-1) and using a gradient of n-heptane:EtOAc (100:0 to 0:100) for the chromatographic purification. Colorless solid (70%). MS (ESI): m/z=400.167 [M+H]+.
Reaction SMILES: N([O-])=O.[Na+].N[C:6]1[CH:11]=[CH:10][C:9]([N:12]([C:17]2[C:36]([CH:37]3[CH2:39][CH2:38]3)=[CH:35][C:20]3[C:21]([C:31]([NH:33][CH3:34])=[O:32])=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[O:23][C:19]=3[CH:18]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:7]=1[C:40]([F:43])([F:42])[F:41].[BrH:44]>C(#N)C.CCOC(C)=O.O.[Cu]Br>[Br:44][C:6]1[CH:11]=[CH:10][C:9]([N:12]([C:17]2[C:36]([CH:37]3[CH2:39][CH2:38]3)=[CH:35][C:20]3[C:21]([C:31]([NH:33][CH3:34])=[O:32])=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[O:23][C:19]=3[CH:18]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:7]=1[C:40]([F:43])([F:42])[F:41]
Reactant: Br
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3ccc(N)c(C(F)(F)F)c3)S(C)(=O)=O)c(C3CC3)cc12
Agent: [Cu]Br
Agent: O=N[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: O
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3ccc(Br)c(C(F)(F)F)c3)S(C)(=O)=O)c(C3CC3)cc12
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 73 %

Procedure:
Sodium nitrite (0.18 g, 2.55 mmol) was added to a 0° C. solution of 6-(N-(4-amino-3-(trifluoromethyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (1.3 g, 2.32 mmol) in acetonitrile (14 ml) and aq HBr (48%) (14 mL). The reaction mixture was stirred for 30 min at 0° C. and copper (I) bromide (0.40 g, 2.78 mmol) was added. The reaction mixture was stirred at 60° C. for 1 h and diluted with EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-50% EtOAc/hexanes) to afford the title compound (1.06 g, 73%) as a white foam. LCMS (m/z, ES+)=625.2, 627.2 (M+H+).
Reaction SMILES: [CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].[N:33]1([C:39](Br)=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>>[CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:21][CH2:22][N:23]([C:39]([N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)=[O:40])[CH2:24][CH2:25]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: O=C(Br)N1CCCCC1
Reactant: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n1C1CCCC1
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(C(=O)N5CCCCC5)CC4)cn3)nc2n1C1CCCC1
Yield: 66.1 %

Procedure:
Following General Procedure G, 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (100 mg, 0.230 mmol) and piperidine-1-carbonyl bromide (32 mL, 0.690 mmol) gave 7-cyclopentyl-2-{5-[4-(piperidine-1-carbonyl)-piperazin-1-yl]-pyridin-2-ylamino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (83 mg, 64%). MS (ESI) m/z 546.3 (M+H)+
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8](=[O:16])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])[CH:5]=[C:4]([CH2:17][CH3:18])[C:3]=1[OH:19].[C:20]([O-])([O-])=O.[K+].[K+].IC>>[Br:1][C:2]1[CH:7]=[C:6]([C:8](=[O:16])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])[CH:5]=[C:4]([CH2:17][CH3:18])[C:3]=1[O:19][CH3:20]
Reactant: O=C([O-])[O-]
Reactant: CCc1cc(C(=O)c2ccccc2Cl)cc(Br)c1O
Agent: [K+]
Solvent: CI
Product: CCc1cc(C(=O)c2ccccc2Cl)cc(Br)c1OC
Reaction time: 48 h
Yield: 66 %

Procedure:
At ambient temperature, to a stirred mixture containing 2-bromo-4-(2-chlorobenzoyl)-6-ethylphenol (14.56 g, 42.82 mmol) and K2CO3 (8.90 g, 64.5 mmol) in N,N-DMF (11.6 mL) was added iodomethane (3.98 mL, 64.4 mmol). After 48 h, the reaction was quenched with H2O (300 mL) and extracted with hexane. The organic extracts were washed with H2O (2×100 mL), brine (1×100 mL), dried (Na2SO4) and concentrated. Purification on Biotage KP-Sil eluting with a 0, 2.5 & 5% EtOAc/hexane step gradient gave 10.0 g (66%) of the title compound. 1H NMR: consistent. mass spectrum (EI) m/z 352 (M+). Anal. Calcd. for C16H14BrClO2.0.2H2O: C, 53.79; H, 4.06; N, 0.00. Found: C, 53.89; H, 3.91; N, 0.08.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:11]([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.O1CCOCC1>[CH3:11][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: O=[N+]([O-])c1cccnc1Cl
Reactant: O=C([O-])[O-]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: C1COCCO1
Product: Cc1ncccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 70.1 %

Procedure:
The mixture of 2-chloro-3-nitropyridine (50 g, 0.315 mol, 1.0 eq), TMB (50 mL, 1.1 eq), (PPh3)4Pd (O) (36.4 g, 0.1 eq), K2CO3 (130.6 g, 3.0 eq) and dioxane (1500 mL) was refluxed under argon for 2 days. The mixture was cooled to room temperature and filtered through a celite pad to remove K2CO3 and catalyst. The celite pad was washed with EtOAc. The organic solutions were combined and concentrated to get the crude which was purified by silica gel chromatography (0%˜40% EtOAc/Hex) to obtain the desired product 2-methyl-3-nitropyridine (30.5 g, isolated yield 70%) (Note: isolated yield 42% was obtained when the reaction was refluxed for 24 h).
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[O:20]C)[C:7]3[CH2:22][C@@H:23]([NH:25][C:26](=[O:31])[O:27][CH:28]([CH3:30])[CH3:29])[CH2:24][C:6]=3[C:5]=2[CH:4]=1)#[N:2].B(Br)(Br)Br>ClCCl>[CH:28]([O:27][C:26](=[O:31])[NH:25][C@@H:23]1[CH2:22][C:7]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[OH:20])[C:9]3[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[C:6]=2[CH2:24]1)([CH3:30])[CH3:29]
Reactant: COc1c(F)cccc1Cn1c2c(c3cc(C#N)ccc31)C[C@H](NC(=O)OC(C)C)C2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC(C)OC(=O)N[C@H]1Cc2c(n(Cc3cccc(F)c3O)c3ccc(C#N)cc23)C1
Reaction time: 8 h
Yield: 64.4 %

Procedure:
To a solution of (S)-isopropyl 7-cyano-4-(3-fluoro-2-methoxybenzyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-ylcarbamate (1.88 g, 4.46 mmol) in dichloromethane (50 mL) is added 1 M boron tribromide in dichloromethane (13.4 mL, 13 4 mmol) at 0° C. and stirred overnight. The reaction is quenched with slightly wet acetonitrile. The volatiles are removed under reduced pressure and the residue is dried under high vacuum. It is then purified by column chromatography with 5% ethyl acetate in chloroform to obtain a yellow solid. The solid is suspended in a minimum amount of dichloromethane and allowed to sit at room temperature. White solids crash out. They are filtered and briefly rinsed with dichloromethane. The mother liquor is concentrated and the procedure is repeated with the residue three times. The white solids are combined to afford the title compound (1.17 g, 64%). LC-ES m/z 408.2 [M+H]+, TR=4.08 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:17]2[C:25]3[C:20](=[C:21]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:22]=[CH:23][CH:24]=3)[CH:19]=[N:18]2)([CH2:15][CH3:16])[CH2:9][CH2:10][C:11]([O:13]C)=O)=[CH:4][CH:3]=1.[CH3:31][Li]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:17]2[C:25]3[C:20](=[C:21]([NH:26][S:27]([CH3:30])(=[O:28])=[O:29])[CH:22]=[CH:23][CH:24]=3)[CH:19]=[N:18]2)([CH2:9][CH2:10][C:11](=[O:13])[CH3:31])[CH2:15][CH3:16])=[CH:4][CH:3]=1
Reactant: [Li]C
Reactant: CCC(CCC(=O)OC)(c1ccc(Cl)cc1)n1ncc2c(NS(C)(=O)=O)cccc21
Solvent: C1CCOC1
Product: CCC(CCC(C)=O)(c1ccc(Cl)cc1)n1ncc2c(NS(C)(=O)=O)cccc21
Reaction time: 0.5 h

Procedure:
A mixture of methyl 4-(4-chlorophenyl)-4-(4-(methylsulfonamido)-1H-indazol-1-yl)hexanoate (50 mg), as described in Example 44 Step E, in 2 mL of anhydrous THF was added CH3Li (1.5 M in ether, 0.2 mL) dropwise at 0° C. and stirred for 30 min. The solution was quenched with saturated NH4Cl solution, and extracted with ethyl acetate (20 mL). The organic layer was washed with brine, dried over dry sodium sulfate, filtered and evaporated. The residue was purified on revered—phase HPLC (0.05% TFA in H2O—MeCN) to give the title product as a white solid. LC/MS m/z=434.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[Se:9][C:10]([CH2:13][OH:14])=[CH:11][N:12]=2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:18]1[CH:26]2[CH:21]([CH:22]3[O:27][CH:25]2[CH2:24][CH2:23]3)[C:20](=[O:28])[CH:19]=1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[Se:9][C:10]([CH2:13][O:14][C:18]3[CH:26]4[CH:21]([CH:22]5[O:27][CH:25]4[CH2:24][CH2:23]5)[C:20](=[O:28])[CH:19]=3)=[CH:11][N:12]=2)=[CH:6][CH:7]=1
Reactant: O=C1C=C(Cl)C2C3CCC(O3)C12
Reactant: OCc1cnc(-c2ccc(Cl)cc2)[se]1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C1C=C(OCc2cnc(-c3ccc(Cl)cc3)[se]2)C2C3CCC(O3)C12
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 77.8 %

Procedure:
To a solution of [2-(4-chlorophenyl)selenazol-5-yl]methanol (300 mg, 1.1 mmol) in dry tetrahydrofuran (5 ml) is added, in one portion, sodium hydride (60% dispersion in mineral oil, 44 mg, 1.1 mmol). The reaction mixture is stirred for 5 minutes at room temperature and 5-chloro-10-oxa-tricyclo[5.2.1.0*2,6*]dec-4-en-3-one (203 mg, 1.1 mmol) is added in one-portion. The reaction mixture is stirred at room temperature overnight. Silica gel is added to the crude reaction mixture, the solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel to give 5-[2-(4-chloro-phenyl)-selenazol-5-ylmethoxy]-10-oxa-tricyclo[5.2.1.0*2,6*]dec-4-en-3-one (360 mg).
Reaction SMILES: [CH:1]([C:3]1[CH:26]=[CH:25][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=3)[O:12][C:13]=2[CH3:14])=[C:5]([O:27][CH3:28])[CH:4]=1)=[O:2].C(O)C.[BH4-].[Na+].O>O1CCCC1>[OH:2][CH2:1][C:3]1[CH:26]=[CH:25][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=3)[O:12][C:13]=2[CH3:14])=[C:5]([O:27][CH3:28])[CH:4]=1
Reactant: COC(=O)c1ccc(-c2nc(COc3ccc(C=O)cc3OC)c(C)o2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: COC(=O)c1ccc(-c2nc(COc3ccc(CO)cc3OC)c(C)o2)cc1
Reaction time: 1 h
Yield: 89.7 %

Procedure:
To a solution of methyl 4-{4-[(4-formyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}benzoate (0.92 g) in tetrahydrofuran (20 mL)-ethanol (10 mL) was gradually added sodium borohydride (0.09 g) at room temperature. After stirring the reaction mixture for 1 hr, water was added, and the precipitated crystals were collected by filtration to give methyl 4-{4-[(4-hydroxymethyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}benzoate as colorless crystals (0.83 g, yield 90%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 170-171° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][CH:25]=1)[CH2:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[CH:15]=2)[NH:10][CH:9]=1)([O-:3])=[O:2].[H-].[Na+].[C:28]1([CH3:38])[CH:33]=[CH:32][C:31]([S:34](Cl)(=[O:36])=[O:35])=[CH:30][CH:29]=1.O>CN(C)C=O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][CH:25]=1)[CH2:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[CH:15]=2)[N:10]([S:34]([C:31]2[CH:32]=[CH:33][C:28]([CH3:38])=[CH:29][CH:30]=2)(=[O:36])=[O:35])[CH:9]=1)([O-:3])=[O:2]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=[N+]([O-])c1cccc(Cc2c[nH]c3ncc(-c4cccnc4)cc23)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)n2cc(Cc3cccc([N+](=O)[O-])c3)c3cc(-c4cccnc4)cnc32)cc1
Reaction time: 3 h

Procedure:
To 3-(3-nitro-benzyl)-5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine (P-1402, 141 mg, 0.43 mmol) in N,N-dimethylformamide (3 mL) was added sodium hydride (60% dispersion in mineral oil, 21 mg, 0.512 mmol) under an atmosphere of nitrogen. After thirty minutes, p-toluenesulfonyl chloride (114 mg, 0.60 mmol) in N,N-dimethyl-formamide was added and the reaction was stirred for three hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated. All solids were filtered and purified by silica gel column chromatography eluting with 40% ethyl acetate in hexane to give the compound (552, 120 mg, 58%). MS (ESI) [M+H+]+=485.25.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[NH:15][C:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:18][CH:17]=3)=[C:13]([C:29]#[N:30])[C:12](=O)[CH:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].P(Cl)(Cl)([Cl:34])=O>>[Cl:34][C:12]1[C:13]([C:29]#[N:30])=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:18][CH:17]=2)[N:15]=[C:10]([C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH:11]=1
Reactant: N#Cc1c(-c2ccc(Oc3ccccc3)cc2)[nH]c(-c2ccc([N+](=O)[O-])cc2)cc1=O
Reactant: O=P(Cl)(Cl)Cl
Product: N#Cc1c(Cl)cc(-c2ccc([N+](=O)[O-])cc2)nc1-c1ccc(Oc2ccccc2)cc1
Temperature: 95 °C
Yield: 61.9 %

Procedure:
A mixture of 6-(4-nitrophenyl)-4-oxo-2-(4-phenoxyphenyl)-1,4-dihydropyridine-3-carbonitrile (211 mg, 0.515 mmol) and phosphoryl trichloride (1 mL, 10.92 mmol) was heated to 95° C. for 30 min, then concentrated. The residue was dissolved in dichloromethane (2 mL) and washed with saturated sodium bicarbonate. Silica gel chromatography, eluting with 0-100% ethyl acetate in hexanes, gave 4-chloro-6-(4-nitrophenyl)-2-(4-phenoxyphenyl)nicotinonitrile as white solid (136.3 mg, 62% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.35-8.41 (2H, m), 8.27-8.33 (2H, m), 8.00-8.06 (2H, m), 7.91 (1H, s), 7.38-7.46 (2H, m), 7.21 (1H, t, J=7.40 Hz), 7.10-7.18 (4H, m); MS (ES+) m/z: 428 (M+14); LC retention time: 4.141 min (analytical HPLC Method A).