Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([CH2:4][CH:5](O)[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([O-:3])=[O:2].CS(Cl)(=O)=O.C(N(CC)CC)C.O>C(Cl)Cl>[N+:1]([CH:4]=[CH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])CC(O)CCc1ccccc1
Agent: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: O=[N+]([O-])C=CCCc1ccccc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 79.9 %

Procedure:
To a solution of 5.85 g (30.0 mmol) of 1nitro-4-phenyl-2-butanol in 40 mL of dry methylene chloride at 0° C. was added 3.44 g (30.0 mmol) of methanesulfonyl chloride followed by addition of 6.07 g (60.0 mmol) of triethylamine. The mixture was stirred at 0° C. for 20 min, poured into 40 mL of water and extracted with 50 mL of methylene chloride. The extracts were dried over sodium sulfate, concentrated, and the residual solid purified by column chromatography (silica gel/ethyl acetate:hexanes 1:9) to afford 4.25 g (80%) of the product as a yellow oil. Since this material slowly decomposes at room temperature, it was used immediately for the next reaction: IR (neat) 3028, 2930, 1648, 1555, 1524, 1497, 1454, 1351, 1176, 953, 931, 750, 700 cm-1 ; 1H NMR (CDCl3) δ 2.63 (2H, q, J=7.0 Hz), 2.87 (2H, t, J=8.0 Hz), 7.00 (1H, dt, J=13.5 Hz), 7.21 (2H, d, J=7.5 Hz), 7.26-7.35 (4H, m); 13C NMR (CDCl3) 5 141.55,140.18, 139.74, 128.90, 128.46, 126.81, 34.19, 30.29; EIMS m/z 177 (M+) 60, 143, 133, 130, 115, 103, 91, 77; HRMS calc'd for C10H11NO2 177.0790, found 177.0802.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1.Cl[CH2:31][C:32]1[O:36][N:35]=[C:34]([CH:37]([CH3:39])[CH3:38])[N:33]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:17][CH2:18][N:19]([CH2:31][C:32]4[O:36][N:35]=[C:34]([CH:37]([CH3:39])[CH3:38])[N:33]=4)[CH2:20][CH2:21]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1
Reactant: Cc1cc(Nc2nc(Nc3cc(C)c(C4CCNCC4)cc3F)ncc2Cl)n[nH]1
Reactant: CC(C)c1noc(CCl)n1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(Nc2nc(Nc3cc(C)c(C4CCN(Cc5nc(C(C)C)no5)CC4)cc3F)ncc2Cl)n[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (42 mg, 0.1 mmol), 5-(chloromethyl)-3-isopropyl-1,2,4-oxadiazole (17 mg, 0.10 mmol) and DIEA (86 μL, 0.5 mmol) in DMF (1 mL) was stirred at rt overnight. The reaction was diluted with EtOAc (50 mL) and washed with water (2×5 mL). The EtOAc layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica chromatography (50-100% EtOAc in hexanes gradient) to give 5-Chloro-N2-(2-fluoro-4-(1-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)piperidin-4-yl)-5-methylphenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as a white solid; ESMS m/z 540.2 (M+H+).
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[C:14]([CH2:15][C@@H:16]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][C:12]([Cl:28])=[C:11]2[C:7]=1[CH:8]=[N:9][NH:10]2)(=[O:3])[CH3:2].[Cl:29]N1C(=O)CCC1=O>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:4][CH2:5][C:6]1[C:14]([CH2:15][C@@H:16]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][C:12]([Cl:28])=[C:11]2[C:7]=1[C:8]([Cl:29])=[N:9][NH:10]2)(=[O:3])[CH3:2]
Reactant: CCOC(=O)C[C@H](Cc1cc(Cl)c2[nH]ncc2c1COC(C)=O)C(=O)OCC
Reactant: O=C1CCC(=O)N1Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)C[C@H](Cc1cc(Cl)c2[nH]nc(Cl)c2c1COC(C)=O)C(=O)OCC
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
(S)-Diethyl 2-((4-(acetoxymethyl)-7-chloro-1H-indazol-5-yl)methyl)succinate (1.12 g, 2.73 mmol) was dissolved in N,N-dimethylformamide (30 ml). Mixture was warmed to 70° C. N-Chlorosuccinimide (400 mg, 3.00 mmol) was added to the solution. Mixture was warmed to 150° C. and held with stirring for 30 minutes. Mixture was cooled to room temperature and then diluted with ethyl acetate. Material was washed twice with 1N sodium thiosulfate and the aqueous phase was discarded. Material was washed successively with water and brine and the aqueous phases were discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as dark amber oil in quantitative yield. MS (M−H)−=443.0.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]([CH3:19])[CH2:16][CH2:17][OH:18])[CH:8]=[CH:9][C:2]1=2.C(N(CC)CC)C.[C:27](Cl)(=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29].[OH-].[Na+]>C(Cl)Cl.O>[C:27]([O:18][CH2:17][CH2:16][N:15]([CH2:14][CH2:13][O:12][CH2:11][CH2:10][C:7]1[CH:8]=[CH:9][C:2]2[S:1][CH:5]=[CH:4][C:3]=2[CH:6]=1)[CH3:19])(=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29]
Reactant: CN(CCO)CCOCCc1ccc2sccc2c1
Reactant: CC(C)(C)C(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CN(CCOCCc1ccc2sccc2c1)CCOC(=O)C(C)(C)C
Temperature: -60 °C
Reaction time: 0.5 h

Procedure:
In 5 mL of methylene chloride is dissolved 0.50 g of 2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl]-(methyl)amino}-1-ethanol. The solution thus obtained is cooled to −60° C., to which are added 0.37 mL of triethylamine and 0.31 mL of pivaloyl chloride. The mixture is stirred at the same temperature as above for 30 minutes and then at ambient temperature for one hour. Water is added to the reaction mixture, pH is adjusted to 9.0 with 1 mol/L aqueous solution of sodium hydroxide, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and the residue is purified by column chromatography (eluent: chloroform:methanol=100:1 to 50:1) to obtain 0.54 g of 2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl](methyl)amino}ethyl pivalate as an oily product.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C:10](=[CH2:13])[C:9]2=[O:14])=[CH:4][CH:3]=1.COC1C=CC=[CH:19][C:18]=1[N:23]1[CH2:28][CH2:27]NCC1.N1CCCC1>O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([CH2:13][N:23]3[CH2:18][CH2:19][CH2:27][CH2:28]3)[C:9]2=[O:14])=[CH:4][CH:3]=1
Reactant: C=C1CCN(c2ccc(Br)cc2)C1=O
Reactant: COc1ccccc1N1CCNCC1
Solvent: C1CCNC1
Solvent: O
Product: O=C1C(CN2CCCC2)CCN1c1ccc(Br)cc1
Yield: 106.6 %

Procedure:
There were mixed 1.31 g of 1-(4-bromophenyl)-3-methylene-2-pyrrolidinone, 2.00 g of 4-(2-methoxyphenyl)piperazine and 5 ml of pyrrolidine. The mixture was refluxed for 1 hour and then cooled. Thereto was added water. The mixture was subjected to extraction with ethyl acetate twice. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography using a mixed solvent of chloroform/methanol=40/1 to obtain 1.79 g of 1-(4-bromophenyl)-3-pyrrolidinomethyl-2-pyrrolidinone.
Reaction SMILES: [F:1][C:2]1[C:3]([NH:9][C:10](=[O:12])[CH3:11])=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH3:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1.CCN(CC)CC>C(Cl)Cl>[F:1][C:2]1[C:3]([NH:9][C:10](=[O:12])[CH3:11])=[N:4][C:5](=[O:8])[N:6]([C:18](=[O:19])[C:17]2[CH:21]=[CH:22][C:14]([CH3:13])=[CH:15][CH:16]=2)[CH:7]=1
Reactant: CC(=O)Nc1nc(=O)[nH]cc1F
Reactant: Cc1ccc(C(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Nc1nc(=O)n(C(=O)c2ccc(C)cc2)cc1F
Temperature: 25 °C
Reaction time: 3 h
Yield: 2.7 %

Procedure:
To a round-bottomed flask containing N-(5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide (350 mg, 2.04 mmol) in CH2Cl2 (20 mL) was added 4-methylbenzoyl chloride (316 mg, 2.2 mmol) and Et3N (454 mg, 4.5 mmol) at 0° C. The mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH2Cl2 (30 mL), washed with saturated aqueous sodium chloride (satd aq NaCl) solution (1×15 mL), dried over Na2SO4 and concentrated in vacuo. The crude solid was purified by reverse phase chromatography to yield N-(5-fluoro-1-(4-methylbenzoyl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide as a white solid (16 mg, 3%): mp 146.9-148.2° C.; 1H NMR (acetone-d6) δ 9.75 (s, 1H), 8.64 (d, J=2.5 Hz, 1H), 8.06 (d, J=8.2 Hz, 2H), 7.44 (d, J=8.1 Hz, 2H), 2.47 (s, 3H), 2.32 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:17][O:18][CH3:19])[O:15][CH2:14][C:13](=O)[NH:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].B.C1COCC1>C1COCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:17][O:18][CH3:19])[O:15][CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COCC1(c2ccc(Cl)c(Cl)c2)CCNC(=O)CO1
Agent: B
Solvent: C1CCOC1
Product: COCC1(c2ccc(Cl)c(Cl)c2)CCNCCO1
Product: Cl
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
To a solution of (7RS)-7-(3,4-dichlorophenyl)-7-(methoxymethyl)-1,4-oxazepan-3-one (535 mg) in THF (10 ml) was added 1 M borane-THF solution (5 ml), and the mixture was stirred at 70° C. for 30 min. The reaction mixture was quenched with water, 2N hydrochloric acid (5 mL) was added, and the mixture was stirred at 70° C. for 10 min. The solvent was evaporated under reduced pressure, the residue was alkalified with potassium hydroxide, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (NH, eluent; hexane:ethyl acetate (1:1)-(0:10)) to give the title compound as a free amine form (397 mg).
Reaction SMILES: Br[CH:2]1[S:6][C:5](=[O:7])[NH:4][C:3]1=[O:8].[CH3:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([SH:16])[N:11]=1>>[CH3:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([S:16][CH:2]2[S:6][C:5](=[O:7])[NH:4][C:3]2=[O:8])[N:11]=1
Reactant: Cc1cccc(S)n1
Reactant: O=C1NC(=O)C(Br)S1
Product: Cc1cccc(SC2SC(=O)NC2=O)n1

Procedure:
This compound was prepared from 5-bromo-thiazolidine-2,4-dione and 2-methyl-6-mercaptopyridine (A. D. Dunn, R. Norrie, J. L'Hostis, and S. Marjot J. Prak. Chem.--Chem. Zt. 1992, 334, 119-125) according to the procedure described in Example 1: mp 114-115.
Reaction SMILES: O[CH2:2][C:3]1[N:4]([CH3:8])[CH:5]=[CH:6][N:7]=1.S(Cl)([Cl:11])=O>>[ClH:11].[Cl:11][CH2:2][C:3]1[N:4]([CH3:8])[CH:5]=[CH:6][N:7]=1
Reactant: Cn1ccnc1CO
Reactant: O=S(Cl)Cl
Product: Cl
Product: Cn1ccnc1CCl
Temperature: 90 °C

Procedure:
To 2-hydroxymethyl-1-methylimidazole (874 mg) was added thionyl chloride (10 ml) at 0° C., and the mixture was heated for 30 minutes under nitrogen atmosphere at 90° C. The mixture was allowed to be at room temperature. The solvent was distilled off under reduced pressure and the obtained residue was recrystallized from ethyl acetate, to give 2-chloromethyl-1-methylimidazole hydrochloride (1.15 g) as brown crystals.
Reaction SMILES: [CH3:1][NH:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[O:12]=[CH:13][C:14]([Cl:17])([Cl:16])[Cl:15]>Cl(O)(=O)(=O)=O>[CH3:1][N:2]([CH:13]([OH:12])[C:14]([Cl:17])([Cl:16])[Cl:15])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4]
Reactant: O=CC(Cl)(Cl)Cl
Reactant: CNC(=O)Nc1ccccc1
Agent: [O-][Cl+3]([O-])([O-])O
Product: CN(C(=O)Nc1ccccc1)C(O)C(Cl)(Cl)Cl

Procedure:
1-methyl-3-phenyl urea (7.5 g, 0.05 mol) was reacted with 7.5 g (0.05 mol) of chloral without solvent. The mixture was shaken for a short period of time. After, three drops of perchloric acid were added and the mixture heated gently for a few minutes to give a homogenous viscous oil. Upon cooling, a glass formed. The chemical analysis showed: %Cl, calculated 35.8, found 35.8; %N, calculated 9.4, found 8.0.
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:5][OH:6])=[O:4].CO.[CH3:9][C:10]([CH:12]=O)=O.[OH-].[Na+]>O>[CH3:12][C:10]1[CH:9]=[N+:5]([O-:6])[C:3]([OH:4])=[CH:2][N:1]=1
Reactant: NCC(=O)NO
Reactant: CC(=O)C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1c[n+]([O-])c(O)cn1
Temperature: 5 °C
Reaction time: 2 h
Yield: 57.7 %

Procedure:
100 mmol (9 g) glycine hydroxamic acid were cooled to −25° C. in 200 ml water and methanol each, 100 mmol (15.4 ml 40% solution) methylglyoxal were added dropwise and subsequently the pH was adjusted to approximately pH 11 with 10 ml 30% NaOH. Heating up to 5° C. was carried out in 2 h and concentrated under vacuum to half of the solvent volume. A pH 3 was adjusted with 20% HCl, precipitated solid was filtered off and dried. 7.28 g (52% yield) of the title compound were obtained.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]2[O:8][C:9]3[C:14]([C@:15]4([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]4)[C:4]=2[CH:3]=1)=[CH:13][C:12]([C:22]1[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=1)=[CH:11][CH:10]=3.[O:29]1[CH2:34][CH:33]=[C:32](B(O)O)[CH2:31][CH2:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[O:29]1[CH2:30][CH:31]=[C:32]([C:2]2[N:7]=[CH:6][C:5]3[O:8][C:9]4[C:14]([C@:15]5([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]5)[C:4]=3[CH:3]=2)=[CH:13][C:12]([C:22]2[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:11][CH:10]=4)[CH2:33][CH2:34]1
Reactant: NC1=N[C@@]2(COC1)c1cc(-c3cccnc3F)ccc1Oc1cnc(Cl)cc12
Reactant: OB(O)C1=CCOCC1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: NC1=N[C@@]2(COC1)c1cc(-c3cccnc3F)ccc1Oc1cnc(C3=CCOCC3)cc12
Temperature: 110 °C
Yield: 92.9 %

Procedure:
A vial was charged with and (S)-3-chloro-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (79.05 mg, 0.199 mmol), 3,6-dihydro-2H-pyran-4-ylboronic acid (76 mg, 0.598 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (7.05 mg, 9.96 μmol), and potassium phosphate (127 mg, 0.598 mmol). Dioxane (747 μL) and water (249 μL) were added, and the vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 110° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (0-10% MeOH/DCM) to give (S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (82.18 mg) as a yellow solid.
Reaction SMILES: [CH:1]([C:4]1[C:9]([CH2:10][OH:11])=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:20])=[O:19])=[CH:14][CH:13]=2)[C:7]([CH:21]=[CH:22][CH2:23][CH2:24][CH3:25])=[C:6]([CH:26]([CH3:28])[CH3:27])[N:5]=1)([CH3:3])[CH3:2].ClC1C=C(C=CC=1)C(OO)=[O:34]>C(Cl)Cl>[CH:1]([C:4]1[C:9]([CH2:10][OH:11])=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:20])(=[O:34])=[O:19])=[CH:14][CH:13]=2)[C:7]([CH:21]=[CH:22][CH2:23][CH2:24][CH3:25])=[C:6]([CH:26]([CH3:27])[CH3:28])[N:5]=1)([CH3:3])[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCC=Cc1c(C(C)C)nc(C(C)C)c(CO)c1-c1ccc(S(C)=O)cc1
Solvent: ClCCl
Product: CCCC=Cc1c(C(C)C)nc(C(C)C)c(CO)c1-c1ccc(S(C)(=O)=O)cc1
Temperature: 0 °C
Yield: 28.7 %

Procedure:
2,6-Diisopropyl-3-hydroxymethyl-4-[4-(methysulfinyl)phenyl]-5-(pent-1-enyl)pyridine (100 mg, 0.261 mmol) (Example 174) was dissolved in methylene chloride (1.5 mL) and stirred at 0° C. under an argon atmosphere. To this mixture was added a solution containing 3-chloroperoxybenzoic acid (“mCPBA”) (85%, 53 mg, 0.261 mmol) in methylene chloride (1 mL). The mixture was stirred for 1.5 h at 0° C. and quenched with the addition of a saturated aqueous solution of NaHO3 (3 mL). The reaction mixture was further diluted through the addition of water (5 mL) and then extracted with methylene chloride (3×10 mL). The combined organic layer was washed sequentially with a saturated aqueous solution of sodium bicarbonate (10 mL) and brine (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The resultant residue was purified by flash chromatography to yield the title compound (31.1 mg, 29%). 1H NMR (300 MHz, CDCl3): δ 0.69 and 0.79 (t, J=7.2 Hz, 3 H), 1.08-1.37 (m, 14 H), 1.45 (t, J=4.2 Hz, 1 H), 1.86-1.93 (m, 2 H), 3.10 and 3.11 (s, 3 H), 3.2-3.50 (m, 2 H), 4.34-4.36 (m, 2 H), 5.20-5.50 (m, 1 H), 5.93-6.00 (m, 1 H), 7.41 (d, J=8.4 Hz, 2 H), 7.96 (d, J=8.4 Hz, 2 H). Anal. calc. for C24H33NO3S: C, 69.28; H, 7.91; N, 3.18; S, 7.50. Found: C, 69.36; H, 8.00; N, 3.37; S, 7.71.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[O:25]1[CH:29]=[CH:28][C:27]([C:30](Cl)=[O:31])=[CH:26]1>>[O:25]1[CH:29]=[CH:28][C:27]([C:30]([NH:1][C:2]2[N:7]=[C:6]3[C:8]([CH:11]4[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH2:13][CH2:12]4)=[CH:9][NH:10][C:5]3=[CH:4][CH:3]=2)=[O:31])=[CH:26]1
Reactant: Nc1ccc2[nH]cc(C3CCN(CCc4ccccc4)CC3)c2n1
Reactant: O=C(Cl)c1ccoc1
Product: O=C(Nc1ccc2[nH]cc(C3CCN(CCc4ccccc4)CC3)c2n1)c1ccoc1

Procedure:
Beginning with 0.015 gm (0.047 mMol) 5-amino-3-(1-(2-phenyleth-1-yl)piperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.008 mL (0.061 mMol) 3-furoyl chloride, the title compound was prepared essentially by the procedure described in Example 7.
Reaction SMILES: [ClH:1].[CH2:2]([O:4][C:5]([C:7]1[S:11][C:10]2[CH:12]=[CH:13][CH:14]=[C:15]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[C:9]=2[CH:8]=1)=[O:6])[CH3:3].Br[CH2:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)(O)[O-].[Na+]>CS(C)=O>[ClH:1].[CH2:2]([O:4][C:5]([C:7]1[S:11][C:10]2[CH:12]=[CH:13][CH:14]=[C:15]([N:16]3[CH2:17][CH2:18][N:19]([CH2:23][CH2:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:20][CH2:21]3)[C:9]=2[CH:8]=1)=[O:6])[CH3:3]
Reactant: CCOC(=O)c1cc2c(N3CCNCC3)cccc2s1
Reactant: BrCCCc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Product: CCOC(=O)c1cc2c(N3CCN(CCCc4ccccc4)CC3)cccc2s1
Yield: 26.9 %

Procedure:
In an analogous manner to example 6, the title compound (0.99 g) as a tan solid, mp 210.5°-213° C., is prepared from ethyl-4-(1-piperazinyl)-benzo[b]thiophene-2-carboxylate monohydrochloride (2.40 g, 8.27 mmol, prepared in example 5), dry dimethyl sulfoxide (45 mL), 1-bromo-3-phenylpropane (1.20 mL, 8.27 mmol) and sodium bicarbonate (0.69 g, 8.27 mmol). Recrystallize the title compound from warm methanol (10 mL); 1H NMR (DMSO-d6) δ 11.05 (bs), 7.76 (1H, d, J=8.2 Hz), 7.49 (1H, t, J=7.9 Hz), 7.28 (5H, m), 7.06 (1H, d, J=7.6 Hz), 4.37 (2H, q, J=7.2 Hz) 3.62 (2H, bd), 3.53 (2H, bd), 3.32 (4H, m), 3.18 (2H, m), 2.69 (2H, m), 1.34 (3H, t, J=7.1 Hz); 13C NMR (DMSO-d6) δ 161.86, 148.25, 142.82, 140.49, 132.62, 131.96, 128.41, 128.33, 128.23, 127.86, 126.11, 117.96, 113.65, 61.49, 55.24, 51.03, 48.76, 32.07, 24.71, 14.16; IR (KBr) 2970, 1709, 1284, 1258 cm-1 ; CI/MS (CH4) 409(100%), 408(75%). IC50 =239 nM (5HT1ABinding Affinity) IC50 =551 nM (5HT1DBinding Affinity)
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[CH3:16][N:17]([CH3:26])[C:18]1[CH:23]=[CH:22][C:21]([CH:24]=[CH2:25])=[CH:20][N:19]=1.[OH-].[K+]>CN1C(=O)CCC1>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([CH2:25][CH2:24][C:21]3[CH:22]=[CH:23][C:18]([N:17]([CH3:26])[CH3:16])=[N:19][CH:20]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1
Reactant: C=Cc1ccc(N(C)C)nc1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN(C)CC3
Agent: [K+]
Agent: [OH-]
Solvent: CN1CCCC1=O
Product: Cc1ccc2c(c1)c1c(n2CCc2ccc(N(C)C)nc2)CCN(C)C1

Procedure:
The title compound is prepared from a mixture of 2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole, N,N-dimethyl-5-vinylpyridin-2-amine and KOH (5-7 equiv) in NMP at a temperature ranging between 25 deg C. to 100 deg C. The product obtained is isolated by preparative HPLC.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:11]2[C@H:7]1[CH2:8][C@@H:9]([OH:25])[C@@:10]2([N:22]=[N+:23]=[N-:24])[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[O:5])[CH3:2].ClC(Cl)(Cl)C(=N)O[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.S(O)(C(F)(F)F)(=O)=O>C1CCCCC1.C(Cl)Cl.CCOCC>[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:11]2[C@H:7]1[CH2:8][C@@H:9]([O:25][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C@@:10]2([N:22]=[N+:23]=[N-:24])[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[O:5])[CH3:2]
Reactant: CCOC(=O)[C@H]1[C@@H]2C[C@@H](O)[C@@](N=[N+]=[N-])(C(=O)OCc3ccccc3)[C@@H]21
Reactant: N=C(OCc1ccccc1)C(Cl)(Cl)Cl
Agent: O=S(=O)(O)C(F)(F)F
Solvent: C1CCCCC1
Solvent: ClCCl
Solvent: CCOCC
Product: CCOC(=O)[C@H]1[C@@H]2C[C@@H](OCc3ccccc3)[C@@](N=[N+]=[N-])(C(=O)OCc3ccccc3)[C@@H]21
Reaction time: 5 h
Yield: 26.6 %

Procedure:
To a solution of (1S,2R,3R,5R,6S)-2-azido-3-hydroxy-bicyclo [3.1.0]hexane-2,6-dicarboxylic acid 2-benzyl ester 6-ethyl ester (VII) (305 mg, 0.88 mmol) and benzyl 2,2,2-trichloroacetimidate (0.2 mL, 1.06 mmol) in cyclohexane (2.4 mL) and DCM (1.2 mL) was added TfOH (0.05 mL), whereupon the solution became hot and stirring was continued at 23° C. for 5 h. The reaction mixture was poured on ice, diluted with ether, washed with sat. NaHCO3 -sol., brine and dried over MgSO4. The crude product was purified by silica gel column chromatography with hexane/EtOAc 4:1 to give (1S,2R,3R,5R,6S)-2-azido-3-benzyloxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-benzyl ester 6-ethyl ester (XXIII-3) (102 mg, 27%) as a yellow oil. 1H-NMR (250 MHz, CDCl3) □1.25 (3H, t, J=7.1 Hz), 1.75 (1H, t, J=3.5 Hz), 2.06 (1H, m), 2.17-2.31 (3H, m), 3.60 (1H, bt, J=8 Hz), 4.12 (2H, q, j=7.1 Hz), 4.42 (1H, d, J=12 Hz), 4.57 (1H, d,J=12 Hz), 5.23 (1H, d,J=12 Hz), 5.34 (1H, d,J=12 Hz), 7.15-7.42 (10H, m); MS[ISP] 408 [(M+H-N2)+ ]; □D20 +2.03 ° (c=0.99, CHCl3).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH3:11])[C:8](=O)[C:7]2[CH:13]=[C:14]3[C:19](=[CH:20][C:6]=2[O:5]1)[CH:18]=[CH:17][CH:16]=[CH:15]3.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:22].[S-2].[K+].[K+]>C1(C)C=CC=CC=1>[Cl:1][CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH3:11])[C:8](=[S:22])[C:7]2[CH:13]=[C:14]3[C:19](=[CH:20][C:6]=2[O:5]1)[CH:18]=[CH:17][CH:16]=[CH:15]3
Reactant: CN1CC(CCCl)Oc2cc3ccccc3cc2C1=O
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Agent: [K+]
Agent: [S-2]
Solvent: Cc1ccccc1
Product: CN1CC(CCCl)Oc2cc3ccccc3cc2C1=S

Procedure:
To a solution of 16.6 g (0.06 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylnaphth[2,3-f][1,4]oxazepin-5(4H)-one in 150 ml of dry toluene was added a mixture of 8.6 g (0.045 mole) of phosphorus pentasulfide and 8.6 g of potassium sulfide which had been ground together. The reaction mixture was stirred and heated at reflux for 24 hr. The mixture was filtered hot and the filtrate concentrated under reduced pressure. Yellow solid, 6.5 g (35%) was obtained which was recrystallized from ethanol, m.p. 166°-168° C.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12]2[NH:13][CH:14]=[CH:15][CH:16]=2)[CH:5]2[O:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=1.BrC1C(OC)=[C:20]([C:25]2[NH:26][CH:27]=CC=2)[CH:21]=[C:22](Br)[CH:23]=1>>[ClH:1].[Cl:1][C:2]1[CH:11]=[C:10]([C:12]2[NH:13][C:14]([CH2:27][N:26]3[CH2:25][CH2:20][CH2:21][CH2:22][CH2:23]3)=[CH:15][CH:16]=2)[CH:5]2[O:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=1
Reactant: COc1c(Br)cc(Br)cc1-c1ccc[nH]1
Reactant: ClC1=CC2=CC=COC2C(c2ccc[nH]2)=C1
Product: Cl
Product: ClC1=CC2=CC=COC2C(c2ccc(CN3CCCCC3)[nH]2)=C1

Procedure:
This compound was prepared by a method analogous to that used to prepare example 1, but using 2-(6-chloro-benzo[b]pyran-8-yl)-1H-pyrrole (prepared according to the method of Kruse et at., [Heterocycles, 26,3141, 1987] from the corresponding acid chloride) in place of 2-(3,5-dibromo-2-methoxyphenyl)-1H-pyrrole.
Reaction SMILES: [Si:1]([O:8][CH:9](C1C=CN=C(C#N)C=1)[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:19]([C:22]1[CH:27]=[C:26](Cl)[CH:25]=[CH:24][N:23]=1)(=[O:21])[CH3:20]>>[C:19]([C:22]1[CH:27]=[C:26]([CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH3:10])[CH:25]=[CH:24][N:23]=1)(=[O:21])[CH3:20]
Reactant: CC(O[Si](C)(C)C(C)(C)C)c1ccnc(C#N)c1
Reactant: CC(=O)c1cc(Cl)ccn1
Product: CC(=O)c1cc(C(C)O[Si](C)(C)C(C)(C)C)ccn1

Procedure:
The title compound was prepared from 4-[1-(tert-butyldimethylsilyloxy)ethyl]-2-pyridinecarbonitrile according to the procedure for preparing 2-acetyl-4-chloropyridine described Example 33.