Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][CH2:5][C:6]1[C:7]([N:28]2[N:37]=[CH:36][C:35]3[C:30](=[C:31]([F:42])[CH:32]=[C:33]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:34]=3)[C:29]2=[O:43])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=2)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=1)(=O)C.O.[OH-].[Li+]>CC(O)C.O1CCCC1>[C:38]([C:33]1[CH:34]=[C:35]2[C:30](=[C:31]([F:42])[CH:32]=1)[C:29](=[O:43])[N:28]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:23]=[C:22]([CH3:24])[N:21]([CH3:25])[N:20]=4)[C:15](=[O:26])[N:14]([CH3:27])[N:13]=3)[CH:10]=[CH:9][N:8]=1)[N:37]=[CH:36]2)([CH3:41])([CH3:39])[CH3:40]
Reactant: CC(=O)OCc1c(-c2cc(Nc3cc(C)n(C)n3)c(=O)n(C)n2)ccnc1-n1ncc2cc(C(C)(C)C)cc(F)c2c1=O
Agent: [Li+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(Nc2cc(-c3ccnc(-n4ncc5cc(C(C)(C)C)cc(F)c5c4=O)c3CO)nn(C)c2=O)nn1C
Temperature: 30 °C
Reaction time: 2 h
Yield: 18.4 %

Procedure:
To a solution of 127c (176 mg, 0.30 mmol) in propan-2-ol (4 mL), tetrahydrofuran (4 mL), and water (1.0 mL) was added lithium hydroxide (72 mg, 3.0 mmol). The mixture was stirred at 30° C. for 2 h. It was then evaporated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 127 (30 mg, 18%) as a white solid. MS-ESI: [M+H]+ 544.8. 1H NMR (500 MHz, MeOD) δ 8.66 (d, J=5.0 Hz, 1H), 8.51 (d, J=2.5 Hz, 1H), 7.88 (s, 1H), 7.88 (s, 1H), 7.76-7.72 (m, 2H), 5.97 (s, 1H), 4.68 (s, 2H), 3.89 (s, 3H), 3.75 (s, 3H), 2.29 (s, 3H), 1.47 (s, 9H)
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:8][CH:9]=[CH:10][N:11]=1.[O:12]1[CH:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:13]1>O>[OH:12][CH:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:13][N:11]1[CH:10]=[CH:9][N:8]=[C:7]1[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1
Reactant: CCCCCCCCCCC1CO1
Reactant: c1ccc(-c2ncc[nH]2)nc1
Solvent: O
Product: CCCCCCCCCCC(O)Cn1ccnc1-c1ccccn1
Temperature: 160 °C
Reaction time: 1 h

Procedure:
A mixture of 14.5 g (0.1 mole) 2-(2-pyridyl)imidazole, 18.4 g (0.1 mole) 1,2-epoxydodecane and 3 drops of water was heated with stirring at about 160° C. under nitrogen for about one hour. The resulting product was then extracted with hot hexane and collected as yellow crystals which had a melting point of 62°-65° C.
Reaction SMILES: [C:1]([O:11][CH2:12][CH3:13])(=[O:10])[CH:2]([CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])[OH:3].[CH2:14](I)[CH3:15]>>[CH2:14]([C:2]([CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])([OH:3])[C:1]([O:11][CH2:12][CH3:13])=[O:10])[CH3:15]
Reactant: CCOC(=O)CC(O)C(=O)OCC
Reactant: CCI
Product: CCOC(=O)CC(O)(CC)C(=O)OCC
Yield: 84 %

Procedure:
Diethyl malate was alkylated with ethyl iodide by following the alkylation method described by Example 12A to provide in 84% yield diethyl ethylmalate as an oil. The product was obtained as a mixture (87:13) of the diastereoisomers represented by the formulas ##STR93##
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[B-](F)(F)(F)[F:12].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C.CC(O)=O>[Cl:1][C:2]1[C:3]2[C:10]([F:12])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Clc1ncnc2[nH]ccc12
Reactant: F[B-](F)(F)F
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CC#N
Solvent: CC(=O)O
Product: Fc1c[nH]c2ncnc(Cl)c12
Temperature: 70 °C
Reaction time: 16 h

Procedure:
4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (F-1) (5.01 g, 32.6 mmol, 1 eq) and selectfluor (17.32 g, 48.9 mmol, 1.5 eq) are dissolved in a mixture of anhydrous acetonitrile (250 mL) and AcOH (50 mL). The resulting mixture is stirred at 70° C. under argon for 16 h. The mixture is concentrated in vacuo. The residue is dissolved in a mixture of DCM-ethyl acetate (v/v=1/1, 50 mL) and filtered through celite. The filtrate is concentrated in vacuo and the residue is purified by flash chromatography on silica gel (0-0.7% MeOH-DCM) to afford the product, 4-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (F-2).
Reaction SMILES: [CH3:1][N:2]([CH3:19])[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][S:9][C:8]2[CH:12]=[C:13]([N+:16]([O-])=O)[CH:14]=[CH:15][C:7]1=2.O.NN>CO.[Ni]>[CH3:19][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][S:9][C:8]2[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][C:7]1=2
Reactant: CN(C)CCCN1CCSc2cc([N+](=O)[O-])ccc21
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CO
Product: CN(C)CCCN1CCSc2cc(N)ccc21
Yield: 99.4 %

Procedure:
A solution of N,N-dimethyl-3-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)propan-1-amine (0.27 g, 0.960 mmol) in dry methanol (10 mL) was treated with hydrazine hydrate (0.349 mL, 9.60 mmol), followed by Raney-Nickel (0.1 g, 0.096 mmol) at room temperature. The resulting mixture was refluxed for 5 minutes in a pre-heated oil bath. The reaction was then brought to room temperature, filtered through a pad of Celite, and washed with methanol (3×10 mL). The combined methanol layers were evaporated, and the crude material was purified by flash column chromatography (5:95 (2 M NH3 in MeOH):CH2Cl2) on silica gel to obtain the title product (0.24 g, 99%) as a syrup. 1H NMR (DMSO-d6) δ 6.50 (dd, 1H, J=2.4, 7.0 Hz), 6.26-6.23 (m, 2H), 4.41 (s, 2H), 3.32-3.30 (m, 2H), 3.09 (t, 2H, J=7.2 Hz), 2.98-2.95 (m, 2H), 2.21 (t, 2H, J=6.9 Hz), 2.11 (s, 6H), 1.63-1.54 (m, 2H); ESI-MS (m/z, %): 252 (MH+, 100).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CCCCCC.[Li+].CCC[CH2-].[CH2:20](Br)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].Cl>O>[CH3:1][N:2]([CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CNc1ccccc1
Reactant: CCCCCCCCCCCCCCCCCCBr
Agent: Cl
Agent: [CH2-]CCC
Agent: [Li+]
Solvent: O
Solvent: CCCCCC
Product: CCCCCCCCCCCCCCCCCCN(C)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Add 23.6 g (0.22 mol) N-methylaniline into 92 g (0.2 mol) 14% hexane solution of N-butyllithium and stir it for 10-20 minutes. Add 33.3 g (0.1 mol) octadecylbromide into the above solution, while stirring it. Add 200 ml water into the solution, after heating and refluxing the solution for about 17 hours and cooling it down to room temperature. Add 6N hydrochloric acid to the solution after concentrating the solution extracted by 300 ml diethyl ether and deposit it. 32.3 g (0.09 mol) N, N-methyloctadecyl-aniline is obtained by refinement through crystaiization with ethyl alcohol and water. Dissolve the obtained 32.3 g (0.09 mol) N, N-methyloctadecyl-aniline into 250 ml concentrated sulfuric acid. Add 30 ml concentrated nitric acid into the solution while stirring it in an ice water bath. Leave it about one hour after adding the nitric acid. Add the solution into ice water, filter off the deposit from it, and refine it by crystallization with ethyl alcohol and water. With the above step, 14.5 g (0.036 mol) N, N-octadecylmethyl-o -nitroaniline is obtained. Add 100 ml 2N hydrochloric acid into this 14.5 g (0.036 mol) N, N-octadecylmethyl-o-nitroaniline which is dissolved into 200 ml ethyl alcohol. 11.7 g (0.031 mol) N, N-octadecylmethyl-o-phenylene-diamine is obtained after adding 11.75 (0.18 mol) zinc dust into the above solution to be heated and refluxed for one hour.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([Cl:19])[C:8]=1[O:9][CH:10]([CH3:18])[C:11]([F:17])([F:16])[C:12]([F:15])([F:14])[F:13])[NH2:5].[F:20][C:21]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:22]=1[C:23]([N:25]=[C:26]=[O:27])=[O:24]>ClCCCl>[F:20][C:21]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:22]=1[C:23]([NH:25][C:26]([NH:5][C:4]1[CH:3]=[C:2]([Cl:1])[C:8]([O:9][CH:10]([CH3:18])[C:11]([F:16])([F:17])[C:12]([F:14])([F:15])[F:13])=[C:7]([Cl:19])[CH:6]=1)=[O:27])=[O:24]
Reactant: O=C=NC(=O)c1c(F)cccc1F
Reactant: CC(Oc1c(Cl)cc(N)cc1Cl)C(F)(F)C(F)(F)F
Solvent: ClCCCl
Product: CC(Oc1c(Cl)cc(NC(=O)NC(=O)c2c(F)cccc2F)cc1Cl)C(F)(F)C(F)(F)F
Temperature: 25 °C

Procedure:
1.0 of 3,5-Dichloro-4-(1-methyl-2,2,3,3,3-pentafluoropropoxy)aniline was placed in a flask to which was added 15 mL of 1,2-dichloroethane. With stirring, 0.62 g 2.6-difluorobenzoyl isocyanate was added all at once to the mixture. The mixture was warmed to near reflux for one hour then cooled to room temperature and stirred overnight. It was then concentrated under vacuum to give 2.30 g crude product. The product was recrystallized from toluene, giving 208 mg of 1-(2,6-difluorobenzoyl)-3-[3,5-dichloro-4-(1-methyl-2,2,3,3,3-pentafluoropropoxy)phenyl]urea. 1H NMR: 10.59 (s, 1H) 9.58 (s, 1H), 7.34 (m, 3H), 7.07 (t, J=8.4 Hz,2H), 5.09 (m, 1H). MS: 506 m/z. IR:1746(s), 1710(s), 1539(s), 1470(m).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][O:4][C:5]1[C:6]([N+:26]([O-])=O)=[C:7]([CH2:12][S:13]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH:8]=[C:9]([F:11])[CH:10]=1.O.NN>C(O)C.[Pd]>[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([CH2:12][S:13]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)(=[O:14])=[O:15])[C:6]=1[NH2:26]
Reactant: O=[N+]([O-])c1c(CS(=O)(=O)c2cccc3ccccc23)cc(F)cc1OCCCl
Agent: [Pd]
Agent: NN
Solvent: O
Solvent: CCO
Product: Nc1c(CS(=O)(=O)c2cccc3ccccc23)cc(F)cc1OCCCl
Temperature: 60 °C

Procedure:
A mixture of 1-[3-(2-chloro-ethoxy)-5-fluoro-2-nitro-phenylmethanesulfonyl]-naphthalene (1.0 g, 2.36 mmoles) in ethanol (25 mL) was stirred under nitrogen in a round bottom flask at 60° C. 10% Pd/C was added, and the temperature was increased to 80° C. Hydrazine hydrate (2.0 mL) was added dropwise and the mixture was stirred at reflux for 3 hours. Reaction mixture was filtered off through Celite, and the solution was washed with H2O (3×), dried over Na2SO4, and concentrated under vacuum to afford the title compound as an off white solid (0.91 g, 2.31 mmoles).
Reaction SMILES: [OH:1][C:2]1[CH:19]=[CH:18][C:5]([C:6](=[O:17])[CH:7]=[CH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH2:22]([CH:24]1[O:26][CH2:25]1)Cl>CN(C)C=O>[O:26]1[CH2:25][CH:24]1[CH2:22][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](=[O:17])[CH:7]=[CH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)=[CH:18][CH:19]=1
Reactant: COc1ccc(C=CC(=O)c2ccc(O)cc2)cc1
Reactant: ClCC1CO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(C=CC(=O)c2ccc(OCC3CO3)cc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a well-stirred solution of 4′-hydroxy-4-methoxy-chalcone, 7 (15 g, 59 mmol) in dry dimethyl formamide (170 mL) was added 50% sodium hydride (5.6 g, 236 mmol) at 0-5° C. and after 30 minutes, excess of epichlorohydrin (13.8 mL, 177 mmol) was added and stirred at room temperature for overnight. The reaction mixture was concentrated under reduced pressure, diluted with water and extracted with chloroform. The combined organic layers were dried over sodium sulphate, filtered and evaporated to dryness. The crude product was purified by column chromatography to afford 13. Yield 11 g (60%); mp 85-87° C.; MS (FAB) 311 (M++1); IR (KBr) 1655; 1H NMR (200 MHz, CDCl3) δ 8.02 (d, J=8.8 Hz, 2H), 7.77 (d, J=15.6 Hz, 1H), 7.59 (d, J=8.7 Hz, 2H), 7.41 (d, J=15.6 Hz, 1H), 6.99 (d, J=8.8 Hz, 2H), 6.93 (d, J=8.7 Hz, 2H), 4.32 (dd, J=11.1 Hz, 2.9 Hz, 1H), 4.01 (dd, J=11.1 Hz, 5.7 Hz, 1H), 3.84 (s, 31H), 3.40-3.35 (m, 1H), 2.92 (t, J=4.5 Hz, 4.5 Hz, 1H), 2.77 (dd, J=4.8 Hz, 2.6 Hz, 1H).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11]Cl)=[CH:7][CH:6]=1)[CH:2]=[CH2:3].NC(N)=[S:15].O.N>C(O)C>[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][SH:15])=[CH:7][CH:6]=1)[CH:2]=[CH2:3]
Reactant: C=CCOc1ccc(CCl)cc1
Reactant: NC(N)=S
Agent: N
Solvent: O
Solvent: CCO
Product: C=CCOc1ccc(CS)cc1
Yield: 80.9 %

Procedure:
A mixture of 2.00 g (10.9 mmol) 1-allyloxy-4-chloromethyl-benzene and 917 mg (12.1 mmol) thiourea in 3.0 ml ethanol was heated to reflux for 7 h. Solvents were distilled off and the crystalline residue was washed with cold ethanol and isolated by filtration. After addition of 2.5 ml ethanol, 1.0 ml water and 0.7 ml 25% aqueous ammonia, the mixture was heated to reflux for 1 h. Ethanol was distilled off, then acidified with 0.5 ml half conc. HCl and extracted with ethyl acetate. The solution was dried over MgSO4 and solvents were removed in vacuo to yield 1.59 g (81%) colourless oil, which was used immediately.
Reaction SMILES: [OH:1][C:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH2:14]([N:21]1[CH2:26][C:25]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([Cl:41])[CH:35]=2)([CH2:27][CH2:28]OS(C)(=O)=O)[CH2:24][O:23][C:22]1=[O:42])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[I-].[K+].Cl>CN(C=O)C.C(Cl)Cl.CCOCC>[ClH:40].[CH2:14]([N:21]1[CH2:26][C:25]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([Cl:41])[CH:35]=2)([CH2:27][CH2:28][N:5]2[CH2:6][CH2:7][C:2]([OH:1])([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:3][CH2:4]2)[CH2:24][O:23][C:22]1=[O:42])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: OC1(c2ccccc2)CCNCC1
Reactant: CS(=O)(=O)OCCC1(c2ccc(Cl)c(Cl)c2)COC(=O)N(Cc2ccccc2)C1
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCOCC
Product: O=C1OCC(CCN2CCC(O)(c3ccccc3)CC2)(c2ccc(Cl)c(Cl)c2)CN1Cc1ccccc1
Yield: 73.9 %

Procedure:
This compound is prepared by the procedure described in step D of EXAMPLE 1 from 1.32 g of 4-hydroxy-4-phenylpiperidine, 1.55 g of the compound obtained in step C of EXAMPLE 1 and 0.56 g of potassium iodide in 10 ml of DMF. The residue is chromatographed on silica H using DCM and then a DCM/MeOH mixture (96/4; v/v) as the eluent. The product obtained is dissolved in DCM and acidified to pH 1 by the addition of a saturated solution of gaseous HCl in ether and the solvents are evaporated off under vacuum to give 0.72 g of the expected compound after crystallization from ether. M.p.=172° C.
Reaction SMILES: Br[C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:16]2[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[C:18]([CH3:24])[N:17]=2)=[CH:10]3)=[CH:4][C:3]=1[F:25].[Li+].[Cl-].C([Sn](CCCC)(CCCC)[C:33]([O:35][CH2:36][CH3:37])=[CH2:34])CCC.[F-].[K+]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:36]([O:35][C:33]([C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:16]2[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[C:18]([CH3:24])[N:17]=2)=[CH:10]3)=[CH:4][C:3]=1[F:25])=[CH2:34])[CH3:37]
Reactant: Cc1nc(-c2cn3c(n2)-c2cc(Br)c(F)cc2OCC3)n(C(C)C)n1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: [Pd]
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Product: C=C(OCC)c1cc2c(cc1F)OCCn1cc(-c3nc(C)nn3C(C)C)nc1-2
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.5 %

Procedure:
To a suspension of 13-bromo-12-fluoro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (2.00 g, 4.93 mmol) and LiCl (620 mg, 14.8 mmol) in dry THF (15 mL), was added tri-n-butyl(1-ethoxyvinyl)tin (1.78 g, 4.93 mmol) and tetrakis(triphenylphosphine) palladium (185 mg, 0.160 mmol) under nitrogen at room temperature. The resultant mixture was heated under 80° C. for 24 h in a seal tube. After cooling down, the mixture was diluted with THF, treated with an aqueous 0.16 M potassium fluoride solution (20 ml), and stirred at ambient temperature for 1 h. The precipitated tri-nbutylstannyl fluoride was removed by filtration. The filtrate was evaporated under reduced pressure to give an aqueous suspension, which was extracted with ethyl acetate. The combined organic layers were washed with water and evaporated in vacuo to give the crude product (1.97 g, over 100% yield) a yellow solid, which was used directly in the next step without further purification. LCMS m/z [M+H]+ 398.1
Reaction SMILES: [F:1][C:2]1[C:3]([OH:21])=[C:4]2[C:9]3=[C:10]([C:12](=[O:19])[C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:14][N:8]3[N:7]([CH3:20])[CH2:6][CH2:5]2)[CH:11]=1.N1C=CC=CC=1.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)(Cl)Cl>[F:1][C:2]1[C:3]([O:21][S:29]([CH3:28])(=[O:31])=[O:30])=[C:4]2[C:9]3=[C:10]([C:12](=[O:19])[CH:13]([C:15]([O:17][CH3:18])=[O:16])[CH2:14][N:8]3[N:7]([CH3:20])[CH2:6][CH2:5]2)[CH:11]=1
Reactant: COC(=O)c1cn2c3c(c(O)c(F)cc3c1=O)CCN2C
Reactant: CS(=O)(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: COC(=O)C1CN2c3c(cc(F)c(OS(C)(=O)=O)c3CCN2C)C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 67.1 %

Procedure:
304 mg of the compound (167) obtained in Example 44 was added to 2 ml of pyridine, and 120 mg of methane-sulfonyl chloride was added to the solution. The solution was stirred for 3 hours at room temperature. 50 ml of chloroform was added to the solution, and the solution was washed with aqueous 5% citric acid solution. The organic layer was separated, and after drying over magnesium sulfate, the solvent was removed by distillation. To the residue, ethanol was added, and the solid matter was filtered off and washed with isopropyl ether to obtain 260 mg of the subject compound (168).
Reaction SMILES: [CH2:1]([N:3]1[C:15]2[CH:14]=[CH:13][C:12]3[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=3[C:10]=2[C:9]2[CH:8]=[C:7]([CH3:20])[CH:6]=[CH:5][C:4]1=2)[CH3:2].CC1C=C2C(=CC=1)NC1C2=CC=C2C=CC=CC2=1>>[CH2:1]([N:3]1[C:15]2[C:10](=[CH:11][CH:19]=[C:18]3[CH:17]=[CH:16][CH:12]=[CH:13][C:14]3=2)[C:9]2[C:4]1=[CH:5][CH:6]=[C:7]([CH3:20])[CH:8]=2)[CH3:2]
Reactant: CCn1c2ccc(C)cc2c2c3ccccc3ccc21
Agent: Cc1ccc2[nH]c3c4ccccc4ccc3c2c1
Product: CCn1c2ccc(C)cc2c2ccc3ccccc3c21
Yield: 76.2 %

Procedure:
Using the procedure outlined in 34A, 8-methyl-11H-benzo[a]carbazole gave a 76.2% yield of 11-ethyl-8-methyl-11H-benzo[a]carbazole, mp 111°-114°, (CH2Cl2 /petroleum ether), (C,H,N).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[O:5][CH2:6][CH2:7][NH2:8].[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=O)[CH:14]=1.[BH4-].[Na+]>CO>[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][NH:8][CH2:7][CH2:6][O:5][C:4]2[CH:9]=[CH:10][CH:11]=[CH:12][C:3]=2[O:2][CH3:1])[CH:14]=1
Reactant: COc1ccccc1OCCN
Reactant: O=Cc1cccnc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1ccccc1OCCNCc1cccnc1
Temperature: 105 °C
Reaction time: 3 h

Procedure:
10 g (0.06 mol) o-Methoxy-phenoxyethylamine were mixed with 6.4 g (0.06 mol) pyridine-3-aldehyde, heated to 105° C and kept at this temperature for 3 hours. The cooled mixture was dissolved in 400 ml methanol. The solution was cooled to 5° C and 5.7 g (0.15 mol) sodium borohydride added in small portions. The mixture was stirred for half an hour at room temperature and then refluxed for 6 hours.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]2[C:14]([OH:15])=[C:13]([C:16]([OH:18])=O)[CH:12]=[N:11][C:10]=12)=[O:5])[CH3:2].[CH3:19][C:20]1[C:28]2([CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=1>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]2[C:14]([OH:15])=[C:13]([C:16]([N:31]3[CH2:32][CH2:33][C:28]4([C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[CH:21]=[C:20]4[CH3:19])[CH2:29][CH2:30]3)=[O:18])[CH:12]=[N:11][C:10]=12)=[O:5])[CH3:2]
Reactant: CC1=Cc2ccccc2C12CCNCC2
Reactant: CCOC(=O)c1cnn2c(O)c(C(=O)O)cnc12
Product: CCOC(=O)c1cnn2c(O)c(C(=O)N3CCC4(CC3)C(C)=Cc3ccccc34)cnc12
Yield: 77.7 %

Procedure:
In the same manner as in Example 19, step 3 and using 3-ethoxycarbonyl-7-hydroxypyrazolo[1,5-a]pyrimidine-6-carboxylic acid (0.533 g, 2.12 mmol) obtained in Example 19, step 2 and 2-methylspiro[inden-1,4′-piperidine] (0.465 g, 2.34 mmol), the title compound (0.712 g, 70%) was obtained.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCCC1>>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[CH2:10][OH:11])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1cccc(F)c1)C(=O)O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@H](CO)Cc1cccc(F)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3-fluorophenyl)propanoic acid [Aldrich] (3.00 g, 10.6 mmol) in tetrahydrofuran (30 mL, 400 mmol) at 0° C. was added 1.0 M borane-THF complex in tetrahydrofuran (32 mL, 32 mmol). The reaction mixture was stirred at room temperature for 3 hrs, cooled with an ice bath, quenched with AcOH:MeOH (1:5, 10 mL and partitioned between saturated aqueous NaHCO3 and DCM. The aqueous phase was then extracted several times with DCM. The combined organic fractions were dried over Na2SO4 and concentrated under reduced pressure. The residue was used directly for the next reaction. LCMS (ES) m/e 270 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C:11]2[CH2:15][CH2:14][CH2:13][CH:12]=2)=[C:4](Cl)[N:3]=1.[I:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[CH2:21][NH2:22]>C(N(CC)CC)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C:11]2[CH2:15][CH2:14][CH2:13][CH:12]=2)=[C:4]([NH:22][CH2:21][C:20]2[CH:23]=[CH:24][CH:25]=[C:18]([I:17])[CH:19]=2)[N:3]=1
Reactant: NCc1cccc(I)c1
Reactant: Clc1nc(Cl)c2ncn(C3=CCCC3)c2n1
Solvent: CCN(CC)CC
Product: Clc1nc(NCc2cccc(I)c2)c2ncn(C3=CCCC3)c2n1

Procedure:
2-Chloro-6-[(3-iodobenzyl)amino]-9-cyclopentenylpurine is prepared from 2,6-dichloro-9-cyclopentenylpurine, 3-iodobenzylamine, and triethylamine essentially as described above in Example 1, Scheme A, step b.
Reaction SMILES: [NH2:1][C@@H:2]([C@@H:38]([C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][CH:48]=1)[C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=1)[C:3]([NH:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([F:37])[C:11]=1[CH2:12][CH2:13][C@H:14]1[O:19][CH2:18][C@@H:17]([CH2:20][O:21][C:22](=[O:29])[NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])[N:16](C(OC(C)(C)C)=O)[CH2:15]1)=[O:4].O1CCOCC1>Cl>[ClH:53].[Cl:53][C:50]1[CH:51]=[CH:52][C:47]([C@@H:38]([C:39]2[CH:40]=[C:41]([F:46])[CH:42]=[C:43]([F:45])[CH:44]=2)[C@@H:2]([C:3]([NH:5][C:6]2[CH:7]=[N:8][CH:9]=[C:10]([F:37])[C:11]=2[CH2:12][CH2:13][C@H:14]2[O:19][CH2:18][C@@H:17]([CH2:20][O:21][C:22](=[O:29])[NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])[NH:16][CH2:15]2)=[O:4])[NH2:1])=[CH:48][CH:49]=1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](CCc2c(F)cncc2NC(=O)[C@@H](N)[C@@H](c2ccc(Cl)cc2)c2cc(F)cc(F)c2)OC[C@H]1COC(=O)NCC(F)(F)F
Agent: Cl
Solvent: C1COCCO1
Product: N[C@H](C(=O)Nc1cncc(F)c1CC[C@@H]1CN[C@H](COC(=O)NCC(F)(F)F)CO1)[C@@H](c1ccc(Cl)cc1)c1cc(F)cc(F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The product from step 3 (60 mg, 0.078 mmol) was dissolved in a solution of 4M HCl in dioxane (1 mL, 4 mmol) and the solution was stirred at ambient temperature for 1 h. The solvent was removed under reduced pressure and the residue was dried in vacuo for 12 h to give an HCl salt of the title compound as a solid. LCMS: RT=0.95 min (2 min gradient), MS (ES) m/z=674.6 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([CH2:9][CH2:10][CH2:11][CH3:12])[CH:6]=[CH:5][C:3]=1[NH2:4].O[CH2:14][CH:15]([CH2:17]O)O>>[CH2:9]([C:7]1[CH:6]=[C:5]2[C:3](=[C:2]([Br:1])[CH:8]=1)[N:4]=[CH:17][CH:15]=[CH:14]2)[CH2:10][CH2:11][CH3:12]
Reactant: CCCCc1ccc(N)c(Br)c1
Reactant: OCC(O)CO
Product: CCCCc1cc(Br)c2ncccc2c1

Procedure:
2-bromo-4-(n-butyl)aniline and glycerol can be combined to form 6-(n-butyl)-8-bromoquinoline,