Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@@:2]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([CH3:24])[C:3]([N:5]1[CH2:23][CH2:22][CH2:21][C@H:6]1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[CH2:18][CH2:19][NH2:20])=[O:8])=[O:4].C(N(CC)CC)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[OH:1][C@@:2]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([CH3:24])[C:3]([N:5]1[CH2:23][CH2:22][CH2:21][C@H:6]1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[CH2:18][CH2:19][NH:20][S:39]([CH3:38])(=[O:41])=[O:40])=[O:8])=[O:4]
Reactant: C[C@](O)(C(=O)N1CCC[C@H]1C(=O)NCc1cc(Cl)ccc1CCN)c1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@](O)(C(=O)N1CCC[C@H]1C(=O)NCc1cc(Cl)ccc1CCNS(C)(=O)=O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of 1-((2R)-2-hydroxy-2-phenylpropanoyl)-N-(2-(2-aminoethyl)-5-chlorobenzyl)-L-prolinamide (90 mg, 0.21 mmol) in CH2Cl2 (2 mL) was added triethylamine (50 microliters, 0.35 mmol) and methanesulfonyl chloride (16 microliters, 0.21 mmol). The mixture was stirred at ambient temperature for 30 min. The mixture was diluted with CH2Cl2 (20 mL) and washed with saturated aqueous sodium bicarbonate solution (10 mL). The organic phase was separated, dried (MgSO4), filtered, and the solvent was removed under reduced pressure to give the title compound as an amorphous solid (TLC Rf=0.2 (98:2 CH2Cl2:MeOH); HPLC RT=3.05 min, method A; LC-MS m/z=508).
Reaction SMILES: [OH:1][C@@H:2]1[CH2:7][N:6]([C:8]([O:10][CH3:11])=[O:9])[C@H:5]([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[O:13])[C@@H:4]([C:26]([O:28][CH3:29])=[O:27])[CH2:3]1.CC(C)([O-])C.[K+].[CH3:36][C:37]([O:40][C:41](=[O:44])[CH2:42]Br)([CH3:39])[CH3:38]>O1CCCC1>[C:37]([O:40][C:41](=[O:44])[CH2:42][O:1][C@@H:2]1[CH2:7][N:6]([C:8]([O:10][CH3:11])=[O:9])[C@H:5]([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[O:13])[C@@H:4]([C:26]([O:28][CH3:29])=[O:27])[CH2:3]1)([CH3:39])([CH3:38])[CH3:36]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: COC(=O)[C@H]1C[C@H](O)CN(C(=O)OC)[C@@H]1C(=O)N1CCN(c2ccccc2)CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)[C@H]1C[C@H](OCC(=O)OC(C)(C)C)CN(C(=O)OC)[C@@H]1C(=O)N1CCN(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of dimethyl (2S,3S,5S)-5-hydroxy-2-[(4-phenylpiperazin-1-yl)carbonyl]piperidine-1,3-dicarboxylate (50.0 mg, 0.000123 mol) in tetrahydrofuran (0.50 mL, 0.0062 mol) was added 1.00 M of potassium tert-butoxide in tetrahydrofuran (0.150 mL). After stirred at rt for 30 min, to the mixture was added bromo-acetic acid 1,1-dimethylethyl ester (0.0228 mL, 0.000154 mol). The resulting mixture was stirred at rt overnight and then concentrated to dry.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[C:9]([CH2:11][NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[N:10]=[C:4]2[CH:3]=1.[C:17]([O:21][C:22]([N:24]1[C@H:28]([CH2:29][F:30])[C@@H:27]([C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)[O:26][C:25]1([CH3:47])[CH3:46])=[O:23])([CH3:20])([CH3:19])[CH3:18].O.C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:17]([O:21][C:22]([N:24]1[C@H:28]([CH2:29][F:30])[C@@H:27]([C:31]2[CH:32]=[CH:33][C:34]([C:2]3[CH:7]=[CH:6][N:5]4[CH:8]=[C:9]([CH2:11][NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[N:10]=[C:4]4[CH:3]=3)=[CH:35][CH:36]=2)[O:26][C:25]1([CH3:47])[CH3:46])=[O:23])([CH3:20])([CH3:18])[CH3:19]
Reactant: CC(C)(C)OC(=O)N1[C@H](CF)[C@@H](c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)OC1(C)C
Reactant: CS(=O)(=O)NCc1cn2ccc(Br)cc2n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CC(C)(C)OC(=O)N1[C@H](CF)[C@@H](c2ccc(-c3ccn4cc(CNS(C)(=O)=O)nc4c3)cc2)OC1(C)C
Yield: 60.4 %

Procedure:
To the solution of N-(7-Bromo-imidazo[1,2-a]pyridin-2-ylmethyl)-methane sulfonamide (71 mg. 0.233 mmol) and (4S,5R)-4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidine-3-carboxylic acid tert-butyl ester (111 mg, 0.256 mmol) in dimethoxyethane:water (2.2 mL:0.5 mL) in a microwave tube is added Na2CO3 (62 mg, 0.583 mmol) at room temperature. The resulting reaction mixture is degassed with nitrogen for 30 minutes then added Pd(PPh3)2Cl2 (9 mg, 0.0116 mmol) and heated in microwave at 120° C. for 2 hours. The solvent is evaporated and purified by flash column chromatography eluting in 2% methanol in CH2Cl2 to afford the title compound (75 mg). 1H-NMR (400 MHz, DMSO-d6) δ: 1.44 (s, 9H), 1.51 (s, 3H), 1.64 (s, 3H), 2.92 (s, 3H), 3.83-3.89 (m, 1H), 4.28 (d, J=6.12 Hz, 2H), 4.45-4.55 (m, 1H), 4.65-4.75 (m, 1H), 5.13 (d, J=7.2 Hz, 1H), 7.27-7.29 (dd, J1=1.6 Hz, J2=7.20 Hz, 1H), 7.56-7.58 (m, 3H), 7.82-7.88 (m, 4H), 8.61 (d, J=7.2 Hz, 1H). LC-MS (m/z): [M+H]=533.1.
Reaction SMILES: Cl.[NH2:2][OH:3].[OH-:4].[Na+].[CH2:6]([CH:8]([C:15](=O)[CH2:16][CH2:17][CH3:18])[CH2:9]C(OCC)=O)[CH3:7].Cl>O>[CH2:6]([C:8]1[C:9](=[O:4])[O:3][NH:2][C:15]=1[CH2:16][CH2:17][CH3:18])[CH3:7]
Reactant: [OH-]
Reactant: NO
Reactant: CCCC(=O)C(CC)CC(=O)OCC
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CCCc1[nH]oc(=O)c1CC
Temperature: 50 °C
Reaction time: 3 h

Procedure:
11.53 g (165.9 mmol) of hydroxylamine hydrochloride are dissolved in 25 ml of water and, at a temperature of at most 0°C., admixed with a solution of 13.27 g (331.8 mmol) of sodium hydroxide in 60 ml of water. Without further cooling, 30.9 g (165.9 mmol) of ethyl 2-ethylhexan-3-onecarboxylate are then added in one portion, and the mixture is stirred at 50° C. for 3 h. For work-up, 15.5 ml of conc. hydrochloric acid are added at 0°C., and the mixture is diluted with water and extracted three times with dichloromethane. The organic phase is dried over sodium sulphate, concentrated and fractionated under high vacuum. B.p.2mbar 105-115°C.
Reaction SMILES: [CH2:1]([NH:18][C:19](=[O:38])[O:20][C@H:21]1[CH2:26][CH2:25][CH2:24][O:23][C@H:22]1[CH2:27][O:28][C:29](=[O:37])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][Br:36])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].[S:39]1[CH:43]=[CH:42][N:41]=[CH:40]1>>[Br-:36].[CH2:1]([NH:18][C:19]([O:20][C@H:21]1[CH2:26][CH2:25][CH2:24][O:23][C@H:22]1[CH2:27][O:28][C:29]([NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][N+:41]1[CH:42]=[CH:43][S:39][CH:40]=1)=[O:37])=[O:38])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCCCCCCCCCCNC(=O)O[C@H]1CCCO[C@H]1COC(=O)NCCCCCBr
Reactant: c1cscn1
Product: CCCCCCCCCCCCCCCCCNC(=O)O[C@H]1CCCO[C@H]1COC(=O)NCCCCC[n+]1ccsc1
Product: [Br-]

Procedure:
Following a procedure similar to that described in Example 4 but using 550.2 mg of dl-cis-2-[N-(5-bromopentyl)carbamoyloxy]methyltetrahydropyran-3-yl N-heptadecylcarbamate (prepared as described in Preparation 67) and 0.65 ml of thiazole, 526.9 mg of the title compound was obtained as a white powder, melting at 115°-120° C.
Reaction SMILES: ClS([N:5]=[C:6]=[O:7])(=O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][CH:27]=1)[C:12]([C:14]1[C:15]([NH:22][CH2:23][CH3:24])=[N:16][C:17]([CH2:20][CH3:21])=[CH:18][CH:19]=1)=O.C(=O)(O)[O-].[Na+].[OH-].[Na+]>O.O1CCCC1>[Cl:8][C:9]1[CH:10]=[C:11]([C:12]2[C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH3:21])=[N:16][C:15]=3[N:22]([CH2:23][CH3:24])[C:6](=[O:7])[N:5]=2)[CH:25]=[CH:26][CH:27]=1
Reactant: CCNc1nc(CC)ccc1C(=O)c1cccc(Cl)c1
Reactant: O=C=NS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCc1ccc2c(-c3cccc(Cl)c3)nc(=O)n(CC)c2n1
Reaction time: 1 h
Yield: 60.2 %

Procedure:
Chlorosulfonyl isocyanate (0.8 ml, 9 mmol) was added to a tetrahydrofuran (50 ml) solution of 3-(3-chlorobenzoyl)-6-ethyl-2-ethylaminopyridine (2.6 g, 9 mmol) under ice-cooling, followed by stirring for 1 hour under ice-cooling. To the reaction solution were added water and saturated sodium bicarbonate aqueous solution in that order, followed by 30 minutes of stirring at room temperature. This was adjusted to pH 10 with 1 N sodium hydroxide aqueous solution and extracted with chloroform. After drying the organic layer over anhydrous magnesium sulfate, magnesium sulfate was removed by filtration and the resulting filtrate was concentrated under a reduced pressure. Thereafter, the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one (1.7 g, 60%) in the form of crystals.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][C:19]=1[N+:20]([O-])=O)[CH2:16][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2.[O:23]=[C:24]1[N:28]2[CH2:29][C:30](=[O:36])[NH:31][C:32]3[CH:33]=[CH:34][CH:35]=[C:26]([C:27]=32)[N:25]1[CH2:37][C:38]([O-])=O.[Na+].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CC(O)=O>[O:15]=[C:7]1[NH:8][C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:14]2[C:6]21[CH2:5][C:4]1[C:17](=[CH:18][C:19]3[N:20]=[C:38]([CH2:37][N:25]4[C:26]5[C:27]6[N:28]([CH2:29][C:30](=[O:36])[NH:31][C:32]=6[CH:33]=[CH:34][CH:35]=5)[C:24]4=[O:23])[NH:1][C:2]=3[CH:3]=1)[CH2:16]2
Reactant: Nc1cc2c(cc1[N+](=O)[O-])C[C@]1(C2)C(=O)Nc2ncccc21
Reactant: O=C([O-])Cn1c(=O)n2c3c(cccc31)NC(=O)C2
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: O=C1Cn2c(=O)n(Cc3nc4cc5c(cc4[nH]3)CC3(C5)C(=O)Nc4ncccc43)c3cccc(c32)N1
Temperature: 60 °C

Procedure:
A mixture of 5,6-diamino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (30 mg, 0.11 mmol, described in Intermediate 13), sodium (2,5-dioxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxalin-1(2H)-yl)acetate (27 mg, 0.10 mmol, described in Intermediate 26), BOP (50 mg, 0.11 mmol), and N,N-diisopropylethylamine (0.019 mL, 0.11 mmol) was stirred in DMF (0.4 mL) at ambient temperature for 2 h, then AcOH (0.4 mL) was added and the resulting mixture was heated to 60° C. for 18 h. The mixture was allowed to cool and the precipitate was isolated by filtration. This solid was washed with H2O, then MeOH, then CH2Cl2, then dried in vacuo to give the title compound. MS: m/z=478 (M+1). HRMS: m/z=478.1606; calculated m/z=478.1622 for C26H20N7O3.
Reaction SMILES: [O:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]3[N:14]=[C:15]([N:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:24][CH2:25][OH:26])[C:16]4[CH2:22][NH:21][CH2:20][CH2:19][C:17]=4[N:18]=3)=[CH:8][CH:7]=2)=[CH:4][N:3]=[CH:2]1.C(N(CC)CC)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>CO.ClCCl>[CH3:40][S:41]([N:21]1[CH2:20][CH2:19][C:17]2[N:18]=[C:13]([NH:12][C:9]3[CH:10]=[CH:11][C:6]([C:5]4[O:1][CH:2]=[N:3][CH:4]=4)=[CH:7][CH:8]=3)[N:14]=[C:15]([N:23]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:24][CH2:25][OH:26])[C:16]=2[CH2:22]1)(=[O:43])=[O:42]
Reactant: OCCN(c1ccccc1)c1nc(Nc2ccc(-c3cnco3)cc2)nc2c1CNCC2
Reactant: CS(=O)(=O)Cl
Solvent: CO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N1CCc2nc(Nc3ccc(-c4cnco4)cc3)nc(N(CCO)c3ccccc3)c2C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 11.4 %

Procedure:
2-((2-(4-(Oxazol-5-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)(phenyl)amino)ethanol (40 mg, 0.09 mmol, Example 1) was dissolved in methanol (0.5 mL) and dichloromethane (3 mL). Triethylamine (0.013 mL, 0.09 mmol) and methanesulfonyl chloride (7.23 μL, 0.09 mmol) were added and the reaction mixture was stirred at room temperature, under nitrogen atmosphere, for 3 h. The solvent was evaporated under reduced pressure, the crude dissolved in few drops of dimethylformamide and acetonitrile, filtered and purified by preparative HPLC yielding 2-((6-(methylsulfonyl)-2-(4-(oxazol-5-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)(phenyl)amino)ethanol (5.2 mg, 10.15%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:13]3[CH:14]=[N:15][CH:16]=[C:12]3[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:17][N:18](C)C=O>O>[C:17]([C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:13]3[CH:14]=[N:15][CH:16]=[C:12]3[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1)#[N:18]
Reactant: CN(C)C=O
Reactant: Brc1ccc(C2CCCc3cncn32)cc1
Solvent: O
Product: N#Cc1ccc(C2CCCc3cncn32)cc1

Procedure:
A mixture of 85 mg of 5-p-bromophenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine and 74 mg of cuprous cyanide in 1 ml of N,N-dimethylformamide is heated under nitrogen at 120° for 11 hours. The reaction mixture is cooled, diluted with 10 ml of water and extracted with ethyl acetate. The organic extracts are dried over sodium sulfate and evaporated. The resulting oil is chromatographed on silica gel with ethyl acetate to yield the title compound, m.p. 117°-118°.
Reaction SMILES: [O:1]1[C@H:3]([CH3:4])[CH2:2]1.[CH2:5]([Mg]Br)[CH2:6][CH2:7][CH:8]=[CH2:9]>>[CH3:4][C@@H:3]([OH:1])[CH2:2][CH2:9][CH2:8][CH2:7][CH:6]=[CH2:5]
Reactant: C=CCCC[Mg]Br
Reactant: C[C@@H]1CO1
Product: C=CCCCC[C@@H](C)O

Procedure:
As shown in the reaction formula 2, the (R)-(+)-1,2-epoxypropane is added to separately synthesized 1M 4-pentenyl magnesium bromide, obtaining a (2R)-7-octen-2-ol (III).
Reaction SMILES: [C:1]([OH:10])(=O)[CH2:2][CH2:3]CC[C:6]([OH:8])=[O:7].[C:11]([OH:22])(=[O:21])[CH2:12][CH:13]([CH2:17][C:18]([OH:20])=[O:19])[C:14]([OH:16])=[O:15].C(C(O)=O)C(C(O)=O)C(C(O)=O)CC(O)=O.C1C(C2OC2)CC2OC2C1>>[C:6](=[O:8])=[O:7].[CH2:1]1[O:10][CH:2]1[CH3:3].[C:11]([OH:22])(=[O:21])[CH2:12][CH:13]([CH2:17][C:18]([OH:20])=[O:19])[C:14]([OH:16])=[O:15]
Reactant: O=C(O)CCCCC(=O)O
Agent: C1CC2OC2CC1C1CO1
Agent: O=C(O)CC(C(=O)O)C(CC(=O)O)C(=O)O
Agent: O=C(O)CC(CC(=O)O)C(=O)O
Product: CC1CO1
Product: O=C=O

Procedure:
After fixing a chain transfer agent to control a molar fraction of —COOH group to 45 relative to a molar fraction of the catalyst and then introducing adipic acid, 5.9 mg (Entries 1 to 5); tricarballylic acid, 5.1 mg (Entries 6 to 10); 1,2,3,4-butane tetracarboxylic acid, 4.7 mg (Entries 11 to 15)) into a reactor, vinylcyclohexene dioxide was weighed to numeral values listed in TABLE 3, relative to the molar fraction of the catalyst and then introduced (into the reactor). Then, polymerization was executed and the catalyst was removed according to the same procedures as described in Example 1, resulting in pure copolymer. TABLE 3 summarizes results of the polymerization. FIG. 2 shows GPC curves of a copolymer obtained by carbon dioxide/propylene oxide copolymerization in the presence of tricarballylic acid (C3H5(CO2H)3) and diepoxide, wherein reference numeral in each curve denotes an entry number in TABLE 2.
Reaction SMILES: [CH:1]1([Na:6])[CH:5]=[CH:4][CH:3]=[CH:2]1.[C:7](=O)([O:10]C)[O:8]C.O1CCC[CH2:14]1>>[CH3:14][C:2]1[C:1]([C:7]([OH:10])=[O:8])([Na:6])[CH:5]=[CH:4][CH:3]=1
Reactant: [Na]C1C=CC=C1
Reactant: COC(=O)OC
Reactant: C1CCOC1
Product: CC1=CC=CC1([Na])C(=O)O
Reaction time: 3 h

Procedure:
5.901 g (33.5 mmol) of the 1,4-dioxane complex of cyclopentadienylsodium were heated with 9.008 g (100.0 mmol) of dimethyl carbonate in 70 ml of tetrahydrofuran to reflux. After 3 h, the solvent and excess dimethyl carbonate were removed distillatively and the residue was washed with 150 ml of diethyl ether. After drying under reduced pressure, 4.68 g (32.03 mmol) of methylcarboxycyclopentadienylsodium were obtained. 2.913 g (19.94 mmol) of methylcarboxycyclopentadienylsodium were admixed with 4.854 g (18.39 mmol) of Mo(CO)6 in 80 ml of tetrahydrofuran, heated for 24 h to reflux, admixed with 4.55 g (32.06 mmol) of methyl iodide after cooling to room temperature and stirred for a further 24 hours at room temperature. After distillative removal of the solvent and the excess methyl iodide under reduced pressure, the crude product was subjected to purification by column chromatography (activated silica gel; cyclohexane:dichloromethane=5:2) to obtain 3.853 g (12.11 mmol) of (η5-methylcarboxycyclopentadienyl)triscarbonylmethylmolybdenum (II) as a yellow powder. 0.4598 g (1.445 mmol) of (η5-methylcarboxycyclopentadienyl)triscarbonylmethylmolybdenum (II) in 20 ml of dichloromethane was gradually admixed at −20° C. with a solution of 0.2169 g (1.4453 mmol) of trifluoromethanesulfonic acid in 5 ml of dichloromethane which caused the yellow solution to turn wine red and vigorous gas formation to occur. The reaction temperature was gradually increased to room temperature in 5° steps at 30 minute intervals. The reaction mixture was then admixed with 25 ml of n-hexane and concentrated under reduced pressure until a wine red product precipitated. The remaining solvent was pipetted off and the solid dried under reduced pressure. 0.443 g (0.9797 mmol, 68% of theory) of (η5-methylcarboxycyclopentadienyl)triscarbonylmolybdenum(II) triflate (I.7) was obtained as a wine red powder.
Reaction SMILES: [CH2:1]([C:3]1[S:7][C:6]([C:8]([C:10]2[CH:15]=[C:14]([Br:16])[CH:13]=[CH:12][C:11]=2[Cl:17])=O)=[CH:5][CH:4]=1)[CH3:2].C(#N)C.C([SiH](CC)CC)C.C(=O)([O-])O.[Na+]>ClCCl>[Br:16][C:14]1[CH:13]=[CH:12][C:11]([Cl:17])=[C:10]([CH2:8][C:6]2[S:7][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=2)[CH:15]=1
Reactant: CCc1ccc(C(=O)c2cc(Br)ccc2Cl)s1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: ClCCl
Product: CCc1ccc(Cc2cc(Br)ccc2Cl)s1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 89.2 %

Procedure:
5-Bromo-2-chlorobenzoic acid (5.00 g) was suspended in dichloromethane (10 ml), and thereto were added oxalyl chloride (2.2 ml) and N,N-dimethylformamide (2 drops). The mixture was stirred at room temperature for 6 hours. The solvent was evaporated under reduced pressure to give 5-bromo-2-chlorobenzoyl chloride. This compound and 2-ethylthiophene (2.38 g) were dissolved in dichloromethane (20 ml), and thereto was added aluminum chloride (3.11 g) at 0° C. The mixture was stirred at the same temperature for one hour. The reaction mixture was poured into a cold 10% aqueous hydrochloric acid solution, and the mixture was extracted with ethyl acetate. The extract was washed successively with 10% aqueous hydrochloric acid solution, water, a saturated aqueous sodium hydrogen carbonate solution, and brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:1) to give 5-bromo-2-chlorophenyl 5-ethyl-2-thienyl ketone (5.29 g) as an oil. APCI-Mass m/Z 329/331 (M+H). (2) A solution of the above 5-bromo-2-chlorophenyl 5-ethyl-2-thienyl ketone (5.29 g) in dichloromethane (50 ml)-acetonitrile (50 ml) was cooled under ice-cooling, and thereto were added dropwise triethylsilane (7.69 ml) and boron trifluoride•diethyl ether complex (6.1 ml). Subsequently, the mixture was stirred at room temperature for 3.5 hours, and was cooled again under ice-cooling. To the mixture was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with chloroform, washed with brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane) to give 5-bromo-2-chloro-1-(5-ethyl-2-thienylmethyl)benzene (4.52 g) as a colorless liquid.
Reaction SMILES: [ClH:1].[C:2]([NH2:5])(=[NH:4])[CH3:3].C[O-].[Na+].[C:9]1([C:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[C:19](=O)[C:18](=[CH:27]N(C)C)[CH2:17][N:16]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl>CO.C(Cl)Cl>[ClH:1].[ClH:1].[CH3:3][C:2]1[N:4]=[CH:27][C:18]2[CH2:17][N:16]=[C:15]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[C:19]=2[N:5]=1
Reactant: CC(=N)N
Reactant: CN(C)C=C1CN=C(c2ccccc2)c2ccccc2C1=O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: Cc1ncc2c(n1)-c1ccccc1C(c1ccccc1)=NC2

Procedure:
In five equal portions 9.0 g (95 mmole) of acetamidine hydrochloride and 22.5 ml (0.1 mole) of a 4.46 M methanol solution of sodium methoxide was added over 3 hr to a solution of 4.5 g (15 mmole) of 1-phenyl-3,4-dihydro-4-[(dimethylamino)methylene]-5H-2-benzazepin-5-one in 180 ml of methanol and 180 ml of methylene chloride. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate, and concentrated at reduced pressure to give an oil. The oil was dissolved in an excess of 6% methanolic hydrogen chloride and the solvent was removed at reduced pressure to dryness. The residue was crystallized from a mixture of ether and methylene chloride to give a white solid mp 211°-221° C. Recrystallization from a mixture of methanol and ether gave white flakes, mp 217°-227° C.
Reaction SMILES: [C:1]([O:4][C:5]1[C:6]([C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:7][C:8]2[O:12][C:11]([CH2:14][OH:15])([CH3:13])[CH2:10][C:9]=2[C:16]=1[C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:3])[CH3:2].C(N(CC)CC)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34].O>ClCCl>[C:1]([O:4][C:5]1[C:6]([C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:7][C:8]2[O:12][C:11]([CH2:14][O:15][S:33]([CH3:32])(=[O:35])=[O:34])([CH3:13])[CH2:10][C:9]=2[C:16]=1[C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(=O)Oc1c(C(C)(C)C)cc2c(c1C(C)(C)C)CC(C)(CO)O2
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1c(C(C)(C)C)cc2c(c1C(C)(C)C)CC(C)(COS(C)(=O)=O)O2
Temperature: 25 °C
Reaction time: 24 h
Yield: 89.2 %

Procedure:
In 50 ml of dichloromethane was dissolved 0.5 g of 5-acetoxy-4,6-di-t-butyl-2-hydroxymethyl-2-methyl-2,3-dihydrobenzofuran synthesized in Example 47 and combined with 0.18 g of triethylamine and 0.2 g of methanesulfonyl chloride, and the mixture was stirred at room temperature for 24 hours. Then, the reaction mixture was combined with water and extracted with ethyl acetate, and the organic layer was washed with 10% hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated. The concentrate was purified by silica gel column chromatography eluting with n-hexane containing 33% ethyl acetate to give 0.55 g of 5-acetoxy-4,6-di-t-butyl-2-methanesulfonyloxymethyl-2-methyl-2,3-dihydrobenzofuran (rotamer mixture) as a colorless oil (yield 89%).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[C:24]([CH3:29])=[N:25][O:26][C:27]=3[CH3:28])=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:36].[Na+].O1CCCC1>CO.C(#N)C>[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:36])[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[C:24]([CH3:29])=[N:25][O:26][C:27]=3[CH3:28])=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: CC(=O)c1cc(Cl)c2cccnc2c1N1CCN(C(=O)c2c(C)noc2C)CC1
Reactant: [BH3-]C#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: CC#N
Product: Cc1noc(C)c1C(=O)N1CCN(c2c(C(C)N)cc(Cl)c3cccnc23)CC1
Temperature: 65 °C

Procedure:
A mixture of 1-(5-chloro-8-{4-[(3,5-dimethylisoxazol-4-yl)carbonyl]piperazin-1-yl}quinolin-7-yl)ethanone (0.044 g, 0.11 mmol) and ammonium acetate (0.0821 g, 1.06 mmol) in methanol (0.4 mL) and acetonitrile (0.4 mL) was heated at 65° C. in a sealed tube for 1 hour. After cooling to room temperature, to the resulting mixture was added 1.0 M sodium cyanoborohydride in tetrahydrofuran (0.26 mL, 0.26 mmol). The reaction was heated at 65° C. overnight. The mixture was cooled to room temperature, quenched with sat. NaHCO3 solution, extracted with dichloromethane, dried over MgSO4 and concentrated to give the desired product. LCMS calculated for C21H23ClN3O2 (M+H)+: m/z=414.2; Found:414.2.