Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH2:3]([SH:5])[CH3:4].F[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[CH2:26][CH2:25][CH2:24][N:16]3[C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:9][CH:8]=1>CN(C)C=O>[CH2:3]([S:5][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[CH2:26][CH2:25][CH2:24][N:16]3[C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:9][CH:8]=1)[CH3:4]
Reactant: Fc1ccc(-c2nc3n(c2-c2ccncc2)CCC3)cc1
Reactant: CCS
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCSc1ccc(-c2nc3n(c2-c2ccncc2)CCC3)cc1
Temperature: 95 °C
Reaction time: 0.5 h

Procedure:
Sodium hydride (60%) (0.75 g, 19 mmol) was added to a solution of ethanethiol (2.1 ml, 1.7 g, 28 mmol) in N,N-dimethylformamide (15 ml) at 0° C. under an argon atmosphere. After stirring for 0.5 hours, 2-(4-fluorophenyl)-3-(4-pyridyl) 6,7-dihydro-[5H]-pyrrolo[1,2-a]-imidazole (3.5 g, 12.5 mmol) of Example 2 was added and the resulting solution heated to 95° C. for 6 hours. The cooled reaction mixture was evaporated under reduced pressure and the residue partitioned between IN aqueous sodium hydroxide and dichloromethane. The organic layer was washed successively with water and brine, dried (magnesium sulfate) and concentrated. The residue was chromatographed on silica gel eluting with 25:1 chloroform/methanol. Fractions containing product were combined, the solvent evaporated and the residue recrystallized from ethyl acetate to afford the titled compound; mp. 124-125° C. Anal. Calcd. for C19H19N3S: C,70 99; H, 5.96; N, 13.08; S, 9.97: Found: C, 70.99; H, 5.92; N, 13.07; S, 9.81.
Reaction SMILES: [CH3:1][C:2]([C:10]1[CH:11]=[C:12]([OH:17])[CH:13]=[C:14]([CH:16]=1)[OH:15])([CH3:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C[O:19][C:20]1[CH2:25][CH:24]=[C:23]([C:26](O)([CH3:28])[CH3:27])[CH2:22][CH:21]=1>ClCCl>[OH:17][C:12]1[C:13]2[C@H:22]3[CH2:21][C:20](=[O:19])[CH2:25][CH2:24][C@H:23]3[C:26]([CH3:28])([CH3:27])[O:15][C:14]=2[CH:16]=[C:10]([C:2]([CH3:1])([CH3:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH:11]=1
Reactant: CCCCCCC(C)(C)c1cc(O)cc(O)c1
Reactant: COC1=CCC(C(C)(C)O)=CC1
Solvent: ClCCl
Product: CCCCCCC(C)(C)c1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(=O)C[C@H]21

Procedure:
The process according to claim 1, said process comprising reacting 5-(1,1-dimethylheptyl)resorcinol with 1-methoxy-4-(1-hydroxy-1-methylethyl)-1,4-cyclohexadiene in the presence of stannic chloride in dichloromethane at a temperature ranging from about -10° C. to about 40° C. to provide dl-cis-1-hydroxy-3-(1,1-dimethylheptyl)-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-one.
Reaction SMILES: C([O:4][CH2:5][CH2:6][C:7]([CH3:15])=[CH:8][CH2:9][CH2:10][C:11](Cl)([CH3:13])[CH3:12])(=O)C.O1CCOCC1.[H][H]>O.[Pd]>[CH3:12][C:11](=[CH:10][CH2:9][CH2:8][CH:7]([CH2:6][CH2:5][OH:4])[CH3:15])[CH3:13]
Reactant: CC(=O)OCCC(C)=CCCC(C)(C)Cl
Reactant: [H][H]
Agent: [Pd]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)=CCCC(C)CCO
Yield: 70 %

Procedure:
1 mole of 7-chloro-3,7-dimethyl-3-octenyl acetate was dissolved into 200 milliliters of dioxane and the solution was subjected to hydrogenation reaction in a reactor containing 20 grams of activated palladium black at about 25° C. under normal pressure until hydrogen was no more absorbed. Then, palladium black was filtered off, from the reaction mixture and dioxane was distilled off from the filtrate under reduced pressure. The residual liquid was added to the solution of 40 grams of sodium hydroxide in 200 milliliters of methanol, and heated under reflux for 72 hours. The resulting reaction mixture was diluted with 1200 milliliters of water, and the oil layer was separated from the aqueous layer. The oil layer thus separated was washed with 200 milliliters of water three times and then dried over 20 grams of Glauber's salt (sodium sulfate). By distillation of the oil layer under reduced pressure a fraction having a boiling point range of 110°-118° C./15mmHg was collected, whereby 0.7 mole of citronellol was obtained.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]1[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][CH:24]([CH3:28])[CH:25]([CH3:27])[CH3:26])[CH:18]=2)[N:9]=1.[CH3:29][C:30]([CH3:32])=O.CO>C(Cl)(Cl)Cl.C(Cl)Cl>[CH3:28][CH:24]([NH:23][C:19]1[CH:18]=[C:17]([C:10]2[N:9]=[C:8]([N:2]3[CH2:3][C@@H:4]4[CH2:7][C@H:1]3[CH2:6][N:5]4[CH:30]([CH3:32])[CH3:29])[N:13]3[CH:14]=[CH:15][N:16]=[C:12]3[CH:11]=2)[CH:22]=[CH:21][N:20]=1)[CH:25]([CH3:27])[CH3:26]
Reactant: CC(C)C(C)Nc1cc(-c2cc3nccn3c(N3CC4CC3CN4)n2)ccn1
Reactant: CC(C)=O
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CC(C)C(C)Nc1cc(-c2cc3nccn3c(N3C[C@@H]4C[C@H]3CN4C(C)C)n2)ccn1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
The mixture of 25 mg (0.066 mmol) {4-[5-(2,5-diaza-bicyclo[2.2.1]hept-2-yl-)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1,2-dimethyl-propyl)-amine in 5 mL chloroform was treated with 38 mg (0.66 mmol) acetone, 41 mg (0.66 mmol) NaBH3(CN) and 1 mL methanol. The mixture was stirred at rt for 15 h. MS showed all starting materials were converted. The mixture was diluted with 100 mL DCM, washed with 20 mL sat. NaHCO3, dried over anhydrous Na2SO4. After purification by chromatography, obtained the title compound as a yellow solid. MS (ES+): 420 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[CH3:12][C:13]1[N:18]=[C:17]([C:19](=[O:21])[CH3:20])[CH:16]=[CH:15][CH:14]=1.CC(C)([O-])C.[K+].C(O)(=O)C>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>[CH3:12][C:13]1[N:18]=[C:17]([C:19](=[O:21])[CH2:20][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][CH:6]=[CH:5]3)[CH:16]=[CH:15][CH:14]=1
Reactant: CC(=O)c1cccc(C)n1
Reactant: Clc1ccc2ncccc2c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Cc1cccc(C(=O)Cc2ccc3ncccc3c2)n1
Temperature: 80 °C
Yield: 78.1 %

Procedure:
To a solution of 6-chloro-quinoline (2.08 g, 12.3 mmol) in tetrahydrofuran (50 mL) was added 1-(6-methyl-pyridin-2-yl)-ethanone of Step B (2.0 g, 14.8 mmol, 1.1 equiv), palladium acetate (0.055 g, 0.25 mmol, 0.02 equiv), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.197 g, 0.50 mmol, 0.04 equiv), and potassium tert-butoxide (3.76 g, 30.75 mmol, 2.2 equiv). The resulting reaction mixture was heated to 80° C. for 18 hours, then cooled down to 20° C., and slowly treated with acetic acid (3 mL). The resulting solids were filtered off, and the mother liquor was concentrated in vacuo. Silica gel chromatography (3:1 hexane/acetone) yielded the title compound (2.52 g, 78%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2([C:17]#[N:18])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[N+:19]([O-])([OH:21])=[O:20]>CC(O)=O.CC(OC(C)=O)=O>[CH3:10][O:9][C:8]1[C:3]([O:2][CH3:1])=[CH:4][C:5]([C:11]2([C:17]#[N:18])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]2)=[C:6]([N+:19]([O-:21])=[O:20])[CH:7]=1
Reactant: COc1ccc(C2(C#N)CCCCC2)cc1OC
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: COc1cc([N+](=O)[O-])c(C2(C#N)CCCCC2)cc1OC
Temperature: 0 °C
Yield: 28.8 %

Procedure:
1-(3,4-Dimethoxyphenyl)cyclohexanecarbonitrile (0.736 g, 3 mmol), prepared in Step 1, was dissolved in HOAc/Ac2O 1/1 (6 mL) was cooled to 0° C. and treated slowly with nitric acid (0.582 g, 6 mmol, 65%). The reaction was left stirring in the ice bath for 10 min, poured into ice and extracted with EtOAc. Organic layer was dried (MgSO4), filtered and concentrated. Purification by flash chromatography (silica gel, 5-25% EtOAc/hexane) afforded (251 mg, 29%) of 1-(4,5-dimethoxy-2-nitrophenyl)cyclohexanecarbonitrile. MS (ESI) m/z 291 (M+H)+.
Reaction SMILES: CC1C=CC(S(OCC2CC3C(F)=CC=C(C4C=CC=CC=4)C=3O2)(=O)=O)=CC=1.[N-]=[N+]=[N-].[Na+].[N:33]([CH2:36][CH:37]1[CH2:41][C:40]2[C:42]([F:52])=[CH:43][CH:44]=[C:45]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:39]=2[O:38]1)=[N+]=[N-].[N-]=[N+]=[N-]>[Pd]>[F:52][C:42]1[C:40]2[CH2:41][CH:37]([CH2:36][NH2:33])[O:38][C:39]=2[C:45]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[CH:44][CH:43]=1
Reactant: [N-]=[N+]=NCC1Cc2c(F)ccc(-c3ccccc3)c2O1
Agent: [Pd]
Agent: Cc1ccc(S(=O)(=O)OCC2Cc3c(F)ccc(-c4ccccc4)c3O2)cc1
Agent: [N-]=[N+]=[N-]
Product: NCC1Cc2c(F)ccc(-c3ccccc3)c2O1
Yield: 43 %

Procedure:
Treatment of (±)-(4-fluoro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (2.03 g, 5.09 mmol) with sodium azide (1.32 g, 20.38 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2-(azidomethyl)-4-fluoro-7-phenyl-2,3-dihydro-1-benzofuran. Treatment of the azide with palladium on carbon (0.137 g, 10 wt. %) generally according to the procedure described for Example 1 gave 0.610 g (43%) of (±)-1-(4-fluoro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine as a white solid, hydrochloride salt. mp 254-257° C.; Anal. calcd. for C15H14FNOHCl: C, 64.4; H, 5.40; N, 5.01. Found: C, 64.98; H, 5.48; N, 4.79.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[C:11]1([S:17]([CH:20]=[CH2:21])(=[O:19])=[O:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CCN(C(C)C)C(C)C>C(#N)C.ClCCl.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:11]1([S:17](/[CH:20]=[CH:21]/[C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)(=[O:19])=[O:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: C=CS(=O)(=O)c1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Solvent: ClCCl
Product: O=S(=O)(/C=C/c1ccc2[nH]ccc2c1)c1ccccc1
Temperature: 25 °C
Yield: 65 %

Procedure:
A solution of 5-bromoindole (5.0 g, 25.5 mmol), phenylvinylsulfone (7.50 g, 44.64 mmol), Pd(OAc)2 (0.46 g, 2.05 mmol), tri-O-tolylphosphine (1.55 g, 5.10 mmol) and DIPEA (3.6 g) was heated to reflux for 18 h in acetonitrile. The reaction mixture was cooled to RT, diluted with dichloromethane and filtered over a bed of filter aid. The solvent is completely distilled off and to the crude fresh dichloromethane was charged. The filtrate was sequentially washed with water and brine, and dried over sodium sulphate. The organic layer was concentrated under vacuum and the product precipitated from ethylacetate and hexane as a solid in about 65-70% yield.
Reaction SMILES: Cl[C:2]1[CH2:8][CH2:7][O:6][C:5]2[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=2[C:3]=1[CH:13]=O.[SH:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.C(OCC)(=O)C>[CH2:20]([O:19][C:17]([C:16]1[S:15][C:2]2[CH2:8][CH2:7][O:6][C:5]3[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=3[C:3]=2[CH:13]=1)=[O:18])[CH3:21]
Reactant: CCOC(=O)CS
Reactant: O=CC1=C(Cl)CCOc2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cc2c(s1)CCOc1ccccc1-2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-chloro-2,3-dihydro-benzo[b]oxepine-5-carbaldehyde (605 mg, 5.8 mmol) in dimethyl formamide (8 ml) at 0° C., was added ethyl 2-mercaptoacetate (640 μl, 5.8 mmol) and potassium carbonate (800 mg, 5.8 mmol). The reaction mixture was stirred at room temperature for 30 minutes and then at 70° C. for 2 hours. The reaction mixture was cooled and diluted with water and ethyl acetate, and the organic phase was washed with brine, dried (MgSO4), and concentrated in-vacuo. Purification on silica gave 4,5-dihydro-6-oxa-3-thia-benzo[e]azulene-2-carboxylic acid ethyl ester.
Reaction SMILES: C([O:3][C:4](=[O:38])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH:12]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([C:23](=[O:36])[NH:24][CH2:25][C:26]3[C:27](=[O:35])[NH:28][C:29]([CH3:34])=[CH:30][C:31]=3[O:32][CH3:33])=[C:15]2[CH3:37])[CH3:13])[CH2:8][CH2:7]1)C.C1COCC1.CO.O.[OH-].[Li+]>O>[CH3:33][O:32][C:31]1[CH:30]=[C:29]([CH3:34])[NH:28][C:27](=[O:35])[C:26]=1[CH2:25][NH:24][C:23]([C:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH:12]([CH:9]2[CH2:8][CH2:7][N:6]([CH2:5][C:4]([OH:38])=[O:3])[CH2:11][CH2:10]2)[CH3:13])[C:15]=1[CH3:37])=[O:36]
Reactant: CCOC(=O)CN1CCC(C(C)n2c(C)c(C(=O)NCc3c(OC)cc(C)[nH]c3=O)c3ccccc32)CC1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n(C(C)C2CCN(CC(=O)O)CC2)c2ccccc12
Temperature: 25 °C
Yield: 81.8 %

Procedure:
To a round bottomed flask was charged with a magnetic stir bar was added (R or S)-ethyl-2-(4-(1-(3-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methylcarbamoyl)-2-methyl-1H-indol-1-yl)ethyl)piperidin-1-yl)acetate (Compound 363) (69 mg, 0.132 mmol), THF (1.5 mL), MeOH (1.5 mL), and water (0.75 mL). To this solution was added lithium hydroxide monohydrate (5.54 mg, 0.132 mmol) and the reaction stirred at room temperature for 1H. The organics were removed under reduced pressure and the resulting aqueous solution purified via reverse phase-HPLC (water/MeCN) 0→95% to afford the title compound (66 mg, 0.108 mmol, 82% yield). LCMS 514 (M+1) 1H NMR (400 MHz, DMSO-d6) δ=11.67 (s, 1H), 9.65 (s, 1H), 7.84-7.68 (m, 2H), 7.63 (d, J=7.4 Hz, 1H), 7.14-7.03 (m, 2H), 6.18 (s, 1H), 4.33 (d, J=3.6 Hz, 2H), 4.27-4.15 (m, 1H), 4.04 (br. s., 2H), 3.85 (s, 3H), 3.57 (s, 1H), 3.35-3.23 (m, 1H), 3.14-2.99 (m, 1H), 2.86-2.74 (m, 1H), 2.62 (s, 3H), 2.21 (s, 3H), 2.18-2.08 (m, 1H), 1.75 (s, 1H), 1.60-1.49 (m, 4H), 1.46-1.33 (m, 1H), 0.92-0.81 (m, 1H).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:16]2[NH:27][C:19]3=[N:20][CH:21]=[C:22]([C:24](O)=[O:25])[CH:23]=[C:18]3[CH:17]=2)[CH2:12][CH:13]([CH3:15])[CH3:14])=[CH:7][CH:6]=1)(=[O:4])=[O:3].Cl.CN.[CH3:31][N:32]1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O.C(OCC)(=O)C>[CH3:31][NH:32][C:24]([C:22]1[CH:23]=[C:18]2[CH:17]=[C:16]([CH:11]([C:8]3[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:9]=3)[CH2:12][CH:13]([CH3:15])[CH3:14])[NH:27][C:19]2=[N:20][CH:21]=1)=[O:25]
Reactant: CN1CCOCC1
Reactant: CC(C)CC(c1ccc(S(C)(=O)=O)cc1)c1cc2cc(C(=O)O)cnc2[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: CN
Agent: Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CNC(=O)c1cnc2[nH]c(C(CC(C)C)c3ccc(S(C)(=O)=O)cc3)cc2c1
Temperature: 25 °C
Reaction time: 14 h
Yield: 11.8 %

Procedure:
To a solution of 2-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (prepared as in Example 1, 432 mg, 1.12 mmol) and methylamine hydrochloride (151 mg, 2.23 mmol) in dichloromethane (8 mL), N,N-dimethylformamide (2 mL) and N-methylmorpholine (370 μL, 3.36 mmol) was added 1-hydroxybenzotriazole hydrate (380 mg, 2.8 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (540 mg, 2.8 mmol) in one portion. The mixture was then stirred at 25° C. for 14 h. The mixture was diluted with ethyl acetate (200 mL), washed with a 1 N aqueous sodium bicarbonate solution, 1 N aqueous hydrochloric acid solution, brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamide (53 mg, 12%) as a white solid: LC/MS m/e calcd for C21H26N3O3S [M+H]+ 400.52, observed 400.2; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (d, J=6.9 Hz, 3H), 0.99 (d, J=6.9 Hz, 3H), 1.52 (m, 1H), 1.96 (m, 1H), 2.11 (m, 1H), 3.04 (s, 3H), 3.08 (d, J=4.4 Hz, 3H), 4.31 (m, 1H), 6.35 (m, 1H), 6.42 (s, 1H), 7.41 (d, J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz, 2H), 8.25 (s, 1H), 8.50 (s, 1H), 10.84 (br. s., 1H).
Reaction SMILES: O.NN.[N:4]1C=CC=CC=1.Cl[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].O>O1CCCC1.C(OCC)(=O)C>[C:11](=[O:12])([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[NH2:4]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: c1ccncc1
Agent: NN
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
The compound obtained in Example 190, (1) (200 mg) was dissolved in tetrahydrofuran (2 ml), pyridine (58 μl) and benzyl chloroformate (68 μl) were added to the solution, and the resulting mixture was stirred at room temperature for 10 minutes. Distilled water and ethyl acetate were added to the reaction mixture, and the layers were separated. The organic layer was washed with saturated aqueous sodium chloride, then dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (ethyl acetate:methanol:28% aqueous ammonia=8:1:0.1) to obtain a benzyl carbamate compound (191 mg). (2) By using the compound obtained in (1) mentioned above (186 mg) as a starting material, a deprotected compound (156 mg) was obtained in the same manner as that of Example 4, (6). (3) By using the compound obtained in (2) mentioned above (60 mg) as a starting material, the compound shown in Table 5 (65 mg) was obtained in the same manner as that of Example 11.
Reaction SMILES: O=[C:2]1[C:9]2[N:5]([CH:6]=[CH:7][CH:8]=2)[CH2:4][CH2:3]1.[CH2:10]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+]>CS(C)=O.[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:10]=[C:2]1[C:9]2[N:5]([CH:6]=[CH:7][CH:8]=2)[CH2:4][CH2:3]1
Reactant: C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C1CCn2cccc21
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [H-]
Solvent: CS(C)=O
Product: C=C1CCn2cccc21
Temperature: 0 °C

Procedure:
A solution of 2,3-dihydro-1-oxo-1H-pyrrolizine (16.1 g, 0.133 m); J. Org. Chem., 27 2468 (1962) ) in dried dimethylsulfoxide (60 ml) is added dropwise over ca. 10 minutes to a mixture of methylenetriphenylphosphorane (from methyl triphenylphosphonium bromide (57.2 g, 0.16 m), sodium hydride 60% dispersion (6.4 g, 0.16 m) and dimethylsulfoxide (256 ml) in the standard fashion (J. Org. Chem., 28 1128 (1963)) at ambient temperatures. After stirring for ca 2 hours, the mixture is heated in an oil-bath set at 70° C. for ca 30 minutes, and let cool. After stirring overnight at ambient temperatures, the mixture is poured into 1200 ml of ice-water, extracted 4×400 ml of ether, the ether layers washed 3×400 ml of water, dried and concentrated to a residue. The residue is extracted well with hexane, the filtered hexane extracts concentrated and distilled to yield 2,3-dihydro-1-methylene-1H-pyrrolizine.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:15][CH2:14][C:13]2[C:12]3[NH:16][CH:17]=[CH:18][C:11]=3[S:10][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].I[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+].N[C@@H]1CCCC[C@H]1N>O1CCOCC1.C(Cl)Cl.[Cu]I>[CH2:1]([O:3][C:4]([N:6]1[CH2:15][CH2:14][C:13]2[C:12]3[N:16]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:17]=[CH:18][C:11]=3[S:10][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCc2sc3cc[nH]c3c2CC1
Reactant: Ic1ccccc1
Agent: [Cu]I
Agent: N[C@@H]1CCCC[C@H]1N
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: ClCCl
Product: CCOC(=O)N1CCc2sc3ccn(-c4ccccc4)c3c2CC1
Temperature: 100 °C
Yield: 92.3 %

Procedure:
To a stirred solution of the product of Example 1, step (g) (0.056 g, 0.21 mmol) in dioxane (1.5 ml) under argon was added iodobenzene (0.026 ml, 0.23 mmol), Cs2CO3 (0.15 g, 0.45 mmol), CuI (0.002 g, 0.01 mmol), and (+)-trans-1,2-diaminocyclohexane (0.005 ml, 0.04 mmol). The reaction mixture was heated to 100° C. until LCMS indicated the reaction was complete (usually 16 hours). The reaction mixture was cooled to RT, diluted with DCM, and filtered through celite. The solvent was evaporated in vacuo and the residue purified by flash silica-gel chromatography (gradient elution: 0 to 50% EtOAc in hexanes) to give the sub-titled compound as a colorless oil (0.066 g). 1H NMR (CD3OD) δ 7.53-7.39 (m, 3H), 7.38-7.32 (m, 2H), 6.92 (d, J=3.0 Hz, 1H), 6.38 (d, J=3.0 Hz, 1H), 4.18-4.06 (m, 2H), 3.68-3.58 (m, 2H), 3.48-3.42 (m, 2H), 3.00-2.94 (m, 2H), 2.54-2.46 (m, 2H), 1.30-1.16 (m, 3H); MS: ESI (positive): 341 (M+H).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[C:10](=[O:11])[N:9]([CH2:12][O:13][CH3:14])[CH:8]=[C:7]([S:15][CH2:16][CH2:17][C:18](OC)=O)[CH:6]=1.CC(C)([O-])C.[K+].Cl[CH2:29][C:30]1C=CC(OC)=[CH:32][CH:31]=1>C1COCC1>[CH2:16]([S:15][C:7]1[CH:6]=[C:5]([O:4][CH2:3][O:2][CH3:1])[C:10](=[O:11])[N:9]([CH2:12][O:13][CH3:14])[CH:8]=1)[C:17]1[CH:18]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: COc1ccc(CCl)cc1
Reactant: COCOc1cc(SCCC(=O)OC)cn(COC)c1=O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COCOc1cc(SCc2ccccc2)cn(COC)c1=O
Reaction time: 16 h
Yield: 82.2 %

Procedure:
A solution of methyl 3-{[5-(methoxymethoxy)-1-(methoxymethyl)-6-oxo-1,6-dihydropyridin-3-yl]sulfanyl}propanoate (Intermediate 16; 300 mg, 0.95 mmol) in THF (5 ml) was cooled to −45° C. and potassium tert-butoxide (117 mg, 0.10 mmol) was added. After stirring at this temperature for 1 hour 1-(chloromethyl)-4-methoxybenzene (154 ml, 1134 mmol) was added and the reaction stirred for 16 hours. The reaction mixture was partitioned between dichloromethane and water. The aqueous layer was re-extracted and the combined organics dried and concentrated under reduced pressure. The resultant residue was purified by column chromatography (SiO2: 80-100% ethyl acetate/petrol) to yield 5-(benzylsulfanyl)-3-(methoxymethoxy)-1-(methoxymethyl)pyridin-2(1H)-one (251 mg, 83%).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[Cl:5][CH:6]([CH3:10])[C:7](Cl)=[O:8].[NH:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][C:12]1=[O:21]>C(=S)=S>[Cl:5][CH:6]([CH3:10])[C:7]([C:17]1[CH:16]=[C:15]2[C:20](=[CH:19][CH:18]=1)[NH:11][C:12](=[O:21])[CH2:13][CH2:14]2)=[O:8]
Reactant: CC(Cl)C(=O)Cl
Reactant: O=C1CCc2ccccc2N1
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: CC(Cl)C(=O)c1ccc2c(c1)CCC(=O)N2

Procedure:
Aluminum chloride (109 g, 817 mmol) was slurried in carbon disulfide (600 mL) and 2-chloropropionyl chloride (16.8 mL, 173.07 mmol) was added. To this mixture was added 3,4-dihydro-2(1H)-quinolone (20.0 g, 135.89 mmol, J. Amer. Chem. Soc., 1944, 66, 1442). The mixture was refluxed for 4 hours, cooled, and the carbon disulfide poured off and discarded. The reddish residue was carefully quenched with ice water which caused the product to solidify. The solids were collected, rinsed well with water, and suctioned dry followed by drying in vacuo. The product weighed 31.37 g (97%) and had mp 205°-206° C. Analysis calculated for C12H12CINO2 : C, 60.64; H, 5.09; N, 5.89. Found: C, 60.20; H, 4.89; N, 5.78.