Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([SH:5])([CH3:4])[CH3:3].[C:6](#[N:9])[CH:7]=[CH2:8].C[O-].[Na+]>>[CH3:1][C:2]([S:5][CH2:8][CH2:7][C:6]#[N:9])([CH3:4])[CH3:3]
Reactant: C=CC#N
Reactant: CC(C)(C)S
Agent: C[O-]
Agent: [Na+]
Product: CC(C)(C)SCCC#N

Procedure:
β-(2-Methyl-2-propylmercapto)propionitrile was prepared according to the procedure of Example 1 using 2-methyl-2-propanethiol according to the procedure of Example 1 using 2-methyl-2-propanethiol (25.0 g; 0.28 moles), acrylonitrile (14.9 g; 0.28 moles) and sodium methoxide (0.5 g).
Reaction SMILES: Cl[C:2]1[C:3]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:4]=2[N:5]([CH3:10])[C:6](=[O:9])[CH2:7][N:8]=1.[OH-].[Cs+].[CH3:18][O:19][C:20]1[CH:42]=[CH:41][C:23]([CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=2)=[CH:22][CH:21]=1>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:15][C:13]1[CH:12]=[CH:11][C:4]2[N:5]([CH3:10])[C:6](=[O:9])[CH2:7][N:8]=[C:2]([C:29]3[CH:28]=[CH:27][C:26]([O:25][CH2:24][C:23]4[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:42][CH:41]=4)=[CH:31][CH:30]=3)[C:3]=2[CH:14]=1
Reactant: CN1C(=O)CN=C(Cl)c2cc(Cl)ccc21
Reactant: COc1ccc(COc2ccc(B3OC(C)(C)C(C)(C)O3)cc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: COc1ccc(COc2ccc(C3=NCC(=O)N(C)c4ccc(Cl)cc43)cc2)cc1
Temperature: 90 °C

Procedure:
(E)-5,7-Dichloro-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (5.00 g, 20.57 mmol), cesium hydroxide (6.91 g, 41.1 mmol), and 2-(4-(4-methoxybenzyloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (9.10 g, 26.7 mmol) were dissolved in dioxane/water (100 mL/30 mL), and the mixture was subjected to vacuum followed by nitrogen gas. The de-gassing was repeated twice, and then tetrakis(triphenylphosphine)palladium (0) (475 mg, 0.41 mmol) was added. The reaction was then heated to 90° C. for 18 hours, and then cooled to room temperature. The crude mixture was diluted with ethyl acetate, and the organic solution was washed with water, then brine, and then dried over sodium sulfate, and concentrated. The crude product was vacuum pulled through a silica plug eluting with 6:4 ethyl acetate:hexanes. The filtrate was concentrated and then washed with methyl-tert-butyl ether. The product was collected as a light yellow solid by filtration (5.13 g, 59%). 1HNMR (300 MHz, CDCl3) δ 3.36 (s, 3H), 3.73 (d, 1H), 3.81 (s, 3H), 4.77 (d, 1H), 5.03 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.27 (d, 1H), 7.32 (d, 1H), 7.36 (d, 2H), 7.49 (dd, 1H), 7.55 (d, 2H).
Reaction SMILES: C([NH:8][C@@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(OC(C)(C)C)=O.[ClH:20].[CH2:21]([O:28][C:29](=[O:35])[C@@H:30]1[CH2:34][CH2:33][CH2:32][NH:31]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[NH2:8][C@@H:9]([C:17]([N:31]1[CH2:32][CH2:33][CH2:34][C@H:30]1[C:29]([O:28][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:35])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1.[ClH:20]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)C(=O)O
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: N[C@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 119.9 %

Procedure:
To a suspension of Boc-D-phenylalanine (42.4 g, 160 mmol) in methylene chloride was added proline benzyl ester hydrochloride (38.7 g, 160 mmol), 1-hydroxybenzotriazole hydrate (21.6 g, 160 mmol) and diisopropylethylamine (83 mL, 480 mmol). Once the solution was homogeneous, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (40 g, 200 mmol) was added. This mixture was allowed to stir at room temperature for 16 hrs and was then concentrated in vacuo. The residue was dissolved in ethyl acetate (500 mL) and this solution was washed twice with saturated aqueous ammonium chloride (400 mL), twice with saturated aqueous bicarbonate (400 mL), and twice with brine (400 mL). The organic solution was dried (MgSO4), filtered and concentrated in vacuo to give 74.6 g (103%) of a straw colored syrup. This syrup was dissolved in p-dioxane (400 mL) and anhydrous HCl gas was bubbled through for 15 minutes and was allowed to stir for 3 hr at room temperature. The solution was concentrated in vacuo to give a yellow foam coating the sides of the flask. The foam was washed several times with diethyl ether and the solvent was decanted. The foam was dried under high vacuum to give 61 g (98%).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][N:4]=1)#[N:2].[CH3:10]N(C=O)C.C([O-])([O-])=O.[K+].[K+].CI>O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][N:4]=1)#[N:2]
Reactant: CN(C)C=O
Reactant: N#Cc1ccc(O)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: O
Product: COc1ccc(C#N)nc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 78 %

Procedure:
2-Cyano-5-hydroxy pyridine (200 mg, 1.66 mmol), DMF (10 mL) and K2CO3 (253 mg, 1.83 mmol), and MeI (354 mg, 2.49 mmol) were combined at rt and the reaction mixture was stirred for 24 h at rt. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with water, dried and concentrated to give 2-cyano-5-methoxy pyridine (175 mg, 78%).
Reaction SMILES: [F:1][C:2]1[C:3]([CH3:12])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[S:46]1[C:50]([C:51]2[N:55]3[CH2:56][CH2:57][NH:58][CH2:59][C:54]3=[N:53][N:52]=2)=[N:49][CH:48]=[N:47]1>CN(C)C=O.C(Cl)Cl>[F:1][C:2]1[C:3]([CH3:12])=[C:4]([C:5]([N:58]2[CH2:57][CH2:56][N:55]3[C:51]([C:50]4[S:46][N:47]=[CH:48][N:49]=4)=[N:52][N:53]=[C:54]3[CH2:59]2)=[O:7])[CH:8]=[CH:9][C:10]=1[F:11]
Reactant: c1nsc(-c2nnc3n2CCNC3)n1
Reactant: Cc1c(C(=O)O)ccc(F)c1F
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1c(C(=O)N2CCn3c(nnc3-c3ncns3)C2)ccc(F)c1F
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
3,4-Difluoro-2-methylbenzoic acid (I68)(124 mg, 0.720 mmol) was dissolved in dry N,N-dimethylformamide (DMF) (4.7 mL) before treating with HATU (274 mg, 0.720 mmol) and DIPEA (0.252 mL, 1.441 mmol) and stirring for 15 mins at RT, under argon before adding 3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (I115)(100 mg, 0.480 mmol) and stirring for a further 18 hours. LCMS confirmed that the desired material was present and that no start material was left. The reaction was worked up by diluting with DCM (50 ml), washing with water (50 ml). The aqueous layer was extracted with DCM (2×30 ml). The combined extracts were washed with brine (30 ml), dried (Na2SO4), filtered and evaporated to afford a pale pink gum. The product was purified on a SNAP 50 g cartridge, eluting with 0-10% MeOH in DCM, the desired fractions were collected and the solvent was evaporated to afford a dark orange gum. Due to presence of residual DMF the crude gum product was diluted with DCM (30 ml), washed with brine (2×20 ml), dried (Na2SO4), filtered and evaporated to afford an orange foam. The foam triturated with n-hexane to afford a pale orange solid. Liquers were removed and the residue was triturated again with n-Hexane. Liquers were removed and the solid was dried overnight in the vac oven at 40° C. to afford desired product in 146 mg as a pale orange solid.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:11][C:12]1[CH:21]=[C:20]2[C:15]([CH:16]=[C:17]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:18]=[N:19]2)=[CH:14][CH:13]=1.N1C=CC=CC=1>C(Cl)(Cl)Cl>[CH2:25]([O:24][C:22]([C:17]1[CH:18]=[N:19][C:20]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[C:12]([NH:11][C:4](=[O:5])[C:3]1[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=1[Br:1])[CH:21]=2)=[O:23])[CH3:26]
Reactant: CCOC(=O)c1cnc2cc(N)ccc2c1
Reactant: O=C(Cl)c1ccccc1Br
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: CCOC(=O)c1cnc2cc(NC(=O)c3ccccc3Br)ccc2c1
Temperature: 25 °C
Yield: 50 %

Procedure:
A solution of 2-bromobenzoyl chloride (5.38 g, 24.5 mmol) in 100 ml chloroform was added dropwise at room temperature to a solution of ethyl 7-aminoquinoline-3-carboxylate (2.65 g, 12.25 mmol), 4-N,N-dimethylaminopyridine (150 mg, 1.23 mmol) and pyridine (3.96 ml, 49 mmol) in 100 ml chloroform. The resulting solution was heated under reflux for 4 hr, then cooled to room temperature. The chloroform solution was then washed sequentially with dilute aqueous hydrochloric acid solution, water and brine, dried over anhydrous sodium sulfate and concentrated to dryness in vacuo. The residue was chromatographed on silica gel, eluting with 60:40 hexane/ethyl acetate to yield the title product as a solid foam (2.45 g 50% yield).
Reaction SMILES: [F:1][C:2]1[CH:28]=[CH:27][C:5]([C:6](=[O:26])[CH2:7][CH2:8][NH:9][C:10]2[C:18]3[C:13](=[CH:14][C:15]([Cl:20])=[CH:16][C:17]=3[Cl:19])[NH:12][C:11]=2[C:21]([O:23]CC)=[O:22])=[CH:4][CH:3]=1.[OH-].[Li+].C(OCC)(=O)C>O1CCCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](=[O:26])[CH2:7][CH2:8][NH:9][C:10]2[C:18]3[C:13](=[CH:14][C:15]([Cl:20])=[CH:16][C:17]=3[Cl:19])[NH:12][C:11]=2[C:21]([OH:23])=[O:22])=[CH:27][CH:28]=1
Reactant: CCOC(=O)c1[nH]c2cc(Cl)cc(Cl)c2c1NCCC(=O)c1ccc(F)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: O=C(CCNc1c(C(=O)O)[nH]c2cc(Cl)cc(Cl)c12)c1ccc(F)cc1
Yield: 86.4 %

Procedure:
Dissolve 3-[(p-fluorophenacyl)methylamino]-2-carbethoxy-4,6-dichloroindole (660 mg, 1.61 mmol) in tetrahydrofuran (5 mL) and water (5 mL). Add lithium hydroxide (203 mg, 4.8 mmol) and stir for 24 hours at room temperature. Dilute the reaction with water (20 mL) and ethyl acetate (50 mL) and acidify. Separate the layers and dry the organic phase over magnesium sulfate, filter and dilute the filtrate with hexane (100 mL). Recrystallize from this solution to yield the title compound as a white powder (550 mg, 90%).
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[N:8]([CH2:9][CH3:10])[N:7]=[C:6]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[CH3:19])[C:5]=1[CH2:20][CH3:21].[CH2:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24][NH:23]1.C(N(CC)CC)C.[OH-].[Na+]>CN(C=O)C.O>[CH2:9]([N:8]1[C:4]([CH2:3][N:23]2[CH2:24][CH2:25][C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:22]2)=[C:5]([CH2:20][CH3:21])[C:6]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[CH3:19])=[N:7]1)[CH3:10]
Reactant: CCc1c(-c2c(C)cc(C)cc2C)nn(CC)c1CCl
Reactant: c1ccc2c(c1)CCNC2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: CCc1c(-c2c(C)cc(C)cc2C)nn(CC)c1CN1CCc2ccccc2C1
Temperature: 100 °C

Procedure:
A mixture of the product of step D (from above) and 1,2,3,4-tetrahydroisoquinoline (150 mg, 1.1 mmol) and triethylamine (1 mL in 5 mL of DMF was heated at 100° C. for 1 hour. The mixture was cooled, diluted with water, basified with 1 N NaOH, and finally extracted with ether. The organic layer was separated, washed with brine, dried over Na2SO4 and concentrated to give about 500 mg of the crude compound as an oil. The oil was purified through silica gel column chromatography to give 160 mg of the title compound as an oil. 1H NMR (CDCl3): 0.90 (t, 3H), 1.39 (t, 3H), 2.05 (s, 6H), 2.25 (q, 2H), 2.31 (s, 3H), 2.76 (q, 2H), 2.90 (q, 2H), 3.66 (s, 2H), 3.68 (s, 2H), 4.24 (q, 2H), 6.90 (s, 2H), 7.05 (m, 1H), 7.15 (m, 3H)ppm.
Reaction SMILES: [C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][NH2:17])=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][NH:17][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:14][CH:13]=1
Reactant: NCc1ccc(Cl)cc1
Reactant: O=C(Cl)Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Cc1ccccc1)NCc1ccc(Cl)cc1

Procedure:
A mixture of (4.0 g, 25.9 mmol) of phenylacetyl chloride, 3.15 mL (25.9 mmol) of 4-chlorobenzylamine and 5.1 mL of triethylamine in 120 mL of methylene chloride was prepared at 0° C. and then heated to reflux under a nitrogen atmosphere for 18 hours. The solvent was evaporated and the residue was treated with 2 mL of 4-chlorobenzylamine and 3 mL of triethylamine and reheated to reflux overnight. After cooling, the mixture was suspended in 100 mL of methylene chloride, washed with 0.5 N hydrochloric acid, 0.5 N sodium hydroxide and saturated aqueous sodium chloride, followed by drying with magnesium sulfate (MgSO4). The solvent was removed in vacuo to give a white solid which was recrystallized from ethyl acetate:hexane to provide N-(4-chlorobenzyl)-phenylacetamide as a white crystalline solid, 4.15 g (62%).
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2([CH2:28][O:29][CH2:30][CH:31]=[CH2:32])[C:25](=[O:26])[NH:24][C:23](=[O:27])[NH:22]2)=[CH:17][CH:16]=1>CC(N(C)C)=O.N.[Cu-]=O>[O:27]=[C:23]1[NH:22][C:21]([C:18]2[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=2)([CH2:28][O:29][CH2:30][CH:31]=[CH2:32])[C:25](=[O:26])[N:24]1[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1
Reactant: C=CCOCC1(c2ccc(F)cc2)NC(=O)NC1=O
Reactant: N#Cc1ccc(Br)cc1C(F)(F)F
Agent: O=[Cu-]
Agent: N
Solvent: CC(=O)N(C)C
Product: C=CCOCC1(c2ccc(F)cc2)NC(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C1=O
Temperature: 160 °C

Procedure:
0.33 g of copper (I) oxide and 0.95 g of 4-bromo-2-trifluoromethylbenzonitrile are added to a solution of 1 g 4-(4-fluorophenyl)-4-[(2-propenyloxy)methyl]imidazolidine-2,5-dione obtained in step 3 in 3 mL of DMAC. The mixture is heated at 160° C. for 3 hours. After cooling, the mixture is diluted with a 50% aqueous ammonia solution and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and evaporated. The crude product is purified by chromatography over silica gel while eluting with 2/1 heptane/ethyl acetate.
Reaction SMILES: C([O:4][CH2:5][C:6]1[C:11]([C:12]#[N:13])=[C:10](Cl)[CH:9]=[C:8]([NH:15][C:16]([NH:18][C@@H:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH3:20])=O)[N:7]=1)(=O)C.[NH2:27][NH2:28].[OH2:29]>C(O)C>[NH2:13][C:12]1[C:11]2[C:6]([CH2:5][OH:4])=[N:7][C:8]([NH:15][C:16]([NH:18][C@@H:19]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH3:20])=[O:29])=[CH:9][C:10]=2[NH:28][N:27]=1
Reactant: O
Reactant: NN
Reactant: CC(=O)OCc1nc(NC(=O)N[C@H](C)c2ccccc2)cc(Cl)c1C#N
Solvent: CCO
Product: C[C@@H](NC(=O)Nc1cc2[nH]nc(N)c2c(CO)n1)c1ccccc1
Temperature: 100 °C

Procedure:
A solution of (R)-(4-chloro-3-cyano-6-(3-(1-phenylethyl)ureido)pyridin-2-yl)methyl acetate (59.1 mg, 0.159 mmol) in ethanol (2 ml) was charged with hydrazine, H2O (46 μl, 0.948 mmol), sealed and heated to 100° C. for 14.5 hr. The mixture was concentrated in vacuo and the residue was purified via flash chromatography (0-20% MeOH/DCM, then 0-20% MeOH/EtOAc) to provide (R)-1-(3-amino-4-(hydroxymethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea. MS ESI calc'd. For C16H19N6O2 [M+H]+ 327. found 327. 1H NMR (ppm, 500 MHz, DMSO-d6) δ 11.51 (s, 1H), 8.91 (s, 1H), 7.33 (m, 5H), 7.22 (m, 1H), 6.00 (t, J=5.6 Hz, 1H), 5.60 (s, 2H), 4.84 (m, 1H), 4.67 (d, J=5.6, 2H), 1.39 (d, J=7.1 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:29](=[O:30])[N:28]([CH3:31])[C:12]2[N:13]([CH3:27])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][C:17]([C:20]1[N:21]=[C:22]([CH2:25][OH:26])[S:23][CH:24]=1)=[CH:16][CH:15]=3.Br[CH2:33][CH:34]1[CH2:36][CH2:35]1>>[CH:34]1([CH2:33][O:26][CH2:25][C:22]2[S:23][CH:24]=[C:20]([C:17]3[CH:18]=[C:19]4[C:14](=[CH:15][CH:16]=3)[N:13]([CH3:27])[C:12]3[N:28]([CH3:31])[C:29](=[O:30])[C:9]([C:3]5[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=5[Cl:1])=[CH:10][C:11]4=3)[N:21]=2)[CH2:36][CH2:35]1
Reactant: BrCC1CC1
Reactant: Cn1c(=O)c(-c2ccc(Cl)cc2Cl)cc2c3cc(-c4csc(CO)n4)ccc3n(C)c21
Product: Cn1c(=O)c(-c2ccc(Cl)cc2Cl)cc2c3cc(-c4csc(COCC5CC5)n4)ccc3n(C)c21

Procedure:
The process is carried out as indicated in Example 10 above, with the compound from Example 9, 3-(2,4-dichlorophenyl)-6-(2-hydroxymethylthiazol-4-yl)-1,9-dimethyl-1,9-dihydropyrido[2,3-b]indol-2-one, and bromomethylcyclopropane.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[CH2:10][CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][C:15]([CH3:21])=[C:16]([CH3:20])[CH:17]=2)[C:12]1=[O:22])(=[O:3])[CH3:2].[CH3:23][C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26][Br:27]>>[Br-:27].[C:1]([C:4]1[CH:5]=[N+:6]([CH2:23][C:24]2[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=2[CH3:26])[CH:7]=[CH:8][C:9]=1[CH2:10][CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][C:15]([CH3:21])=[C:16]([CH3:20])[CH:17]=2)[C:12]1=[O:22])(=[O:3])[CH3:2]
Reactant: Cc1ccccc1CBr
Reactant: CC(=O)c1cnccc1CC1Cc2cc(C)c(C)cc2C1=O
Product: CC(=O)c1c[n+](Cc2ccccc2C)ccc1CC1Cc2cc(C)c(C)cc2C1=O
Product: [Br-]

Procedure:
The title compound 152 is prepared according to the procedure reported in Example 38.1 with compound 111 (41.1 mg, 0.14 mmol) and 2-methylbenzyl bromide (32 μL, 0.24 mmol) as reactants. Pale yellow solid. (Yield 66 mg, 97%).
Reaction SMILES: [NH:1]1[C:9]2[C:4]3[C:5](=[CH:10][CH:11]=[CH:12][C:3]=3[C:2]1=[O:13])[CH:6]=[CH:7][CH:8]=2.[H-].[Na+].CI.[C:18](OCC)(=O)C>CN(C)C=O.O>[CH3:18][N:1]1[C:9]2[C:4]3[C:5](=[CH:10][CH:11]=[CH:12][C:3]=3[C:2]1=[O:13])[CH:6]=[CH:7][CH:8]=2
Reactant: O=C1Nc2cccc3cccc1c23
Reactant: CCOC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: CN(C)C=O
Solvent: O
Product: CN1C(=O)c2cccc3cccc1c23
Reaction time: 0.33 h

Procedure:
Benz[cd]indole-2(1H)-one (5.1 g, 30 mmol) was dissolved in anhydrous N,N-dimethylformamide (100 ml). Thereto was added sodium hydride (60% content, 1.2 g, 30 mmol), and the resulting solution was stirred for 20 minutes in an ice bath. The reaction solution was mixed with methyl iodide (2.6 ml, 42 mmol) and again stirred at a room temperature for 1 hour. The reaction solution was mixed with ethyl acetate (300 ml) and water (200 ml), and the reaction product was extracted with ethyl acetate. The ethyl acetate layer was separated, washed with water and then dried with anhydrous sodium sulfate. By evaporating ethyl acetate under a reduced pressure, 4.7 g (26 mmol, 74% in yield) of the title compound was obtained as yellow crystals.
Reaction SMILES: [OH:1][B:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=3)=[CH:10][C:5]=2[CH2:4][O:3]1.[CH3:21][N:22]([CH2:24][CH2:25]O)[CH3:23].CCN=C=NCCCN(C)C>CN(C=O)C>[CH3:21][N:22]([CH3:23])[CH2:24][CH2:25][O:17][C:16](=[O:18])[C:15]1[CH:14]=[CH:13][C:12]([O:11][C:9]2[CH:8]=[CH:7][C:6]3[B:2]([OH:1])[O:3][CH2:4][C:5]=3[CH:10]=2)=[CH:20][CH:19]=1
Reactant: CN(C)CCO
Reactant: O=C(O)c1ccc(Oc2ccc3c(c2)COB3O)cc1
Agent: CCN=C=NCCCN(C)C
Solvent: CN(C)C=O
Product: CN(C)CCOC(=O)c1ccc(Oc2ccc3c(c2)COB3O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 58.6 %

Procedure:
To a clear solution of 4-(1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-benzoic acid ((C38), 0.5 g, 1.75 mmol) in DMF (20 mL) were added N,N-dimethylamino ethanol (0.37 mL, 3.7 mmol) and EDCI (0.71 g, 3.7 mmol). The reaction was stirred at room temperature overnight. Then DMF was evaporated under vacuum. The residue was purified over sililca gel, eluting with 5% MeOH/DCM, to afford the 0.35 g of the title compound in 56% yield. 1H NMR 400 MHz (DMSO-d6) δ: 7.97 (d, J=8.9 Hz, 2H), 7.76 (d, J=7.8 Hz, 1H), 7.15-7.07 (m, 4H), 4.95 (s, 2H), 4.33 (t, J=5.5 Hz, 2H), 2.58 (t, J=5.9 Hz, 2H), 2.20 (s, 6H); MS (ES) m/z: 342 (M+H)'; HPLC purity: 91.90% (220 nm), 94.99% (254 nm).
Reaction SMILES: [ClH:1].C[C:3]1C=C2[C:6]([NH:7]C=C2CCN)=[C:5](Br)[CH:4]=1.Cl.[CH3:17][C:18]1[CH:19]=[C:20]([NH:25]N)[CH:21]=[C:22]([CH3:24])[CH:23]=1>>[ClH:1].[CH3:17][C:18]1[CH:23]=[C:22]([CH3:24])[CH:21]=[C:20]2[C:19]=1[C:4]([CH2:5][CH2:6][NH2:7])=[CH:3][NH:25]2
Reactant: Cc1cc(Br)c2[nH]cc(CCN)c2c1
Reactant: Cc1cc(C)cc(NN)c1
Agent: Cl
Product: Cc1cc(C)c2c(CCN)c[nH]c2c1

Procedure:
4,6-Dimethyltryptamine hydrochloride was prepared (1.06 g) as described for 5-methyl-7-bromotryptamine hydrochloride in Example 4, except using 3,5-dimethylphenylhydrazine hydrochloride (7.65 g) as starting material.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[Br:7][C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][C:9]=1[Cl:15].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH2:2]([N:12]([CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[C:11]1[CH:13]=[CH:14][C:8]([Br:7])=[C:9]([Cl:15])[CH:10]=1)[CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: Nc1ccc(Br)c(Cl)c1
Reactant: CCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCN(CCCCC)c1ccc(Br)c(Cl)c1
Yield: 106.4 %

Procedure:
1-Bromopentane (0.42 mL, 3.4 mmol) was added to a mixture of 4-bromo-3-chloroaniline (200 mg, 0.9 mmol) and potassium carbonate (199 mg, 1.4 mmol) in DMF (20 mL) and the reaction was heated to 13 0˜˜C overnight. The mixture was cooled, diluted with water (20 mL) and extracted with petroleum ether (3×25mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified via flash column chromatography using 9:1 petroleum ether:ethyl acetate as eluent to give N,N-Dipentyl-4-bromo-3-chloroaniline (1) (332 mg, 68%). 1HNMR (CDCI3) 67.02 (d, IH, ArH); 3.12 (t, 4H, 2×NCH2); 0.95 (t, 6H, 2×CH3). MS; 347 (M+H).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH:13]=[CH:12]2)=[C:4]([NH2:17])[N:3]=1.[O-:18][CH2:19][CH3:20].[Na+].Cl>C(O)C>[CH:11]1([N:8]2[CH:7]=[N:6][C:5]3[C:9]2=[N:10][C:2]([O:18][CH2:19][CH3:20])=[N:3][C:4]=3[NH2:17])[CH2:16][CH2:15][CH2:14][CH:13]=[CH:12]1
Reactant: Nc1nc(Cl)nc2c1ncn2C1C=CCCC1
Reactant: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOc1nc(N)c2ncn(C3C=CCCC3)c2n1
Temperature: 0 °C
Yield: 92 %

Procedure:
A mixture of 2-chloro-9-(2-cyclohexenyl)-9H-adenine (310 mg., 1.24 mmole) and a solution of sodium ethoxide in ethanol (0.25-1 N, ~10 ml.) was refluxed overnight under an atmosphere of nitrogen. The reaction mixture was poured into ice-water, neutralized with 1 N HCl and extracted with ethyl acetate (20 ml.). The extracts were washed with water, dried over Na2SO4 and filtered. The filtrate was evaporated and the residue then subjected to silica gel chromatography (silica gel 7 g., eluted with 1% CH3OH--CHCl3) to give the title product in 92% yield; m.p. 67°-72° C. IR(KBr): 3320, 2940, 1640, 1595, 1465, 1410, 1385, 1340 cm-1. UV: λmaxEtOH 254 nm(ε8400), 269 nm(ε12600). NMR(CDCl3): 1.44 (3H, t, J=7 Hz), 2.00(6H, m), 4.45(2H, q, J=7 Hz), 5.20(1H, m), 5.95(2H, m), 6.16(2H, s), 7.62(1H, s).