Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2](Cl)(Cl)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].[CH2:34](Br)CCCCCCCCCCCCCCCCCCC.C([Mg]Br)=CCCCCCCCCC>>[CH3:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:34]
Reactant: CCCCCCCCCCCCCCCCCCCCBr
Reactant: CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(Cl)(Cl)Cl
Agent: CCCCCCCCCC=C[Mg]Br
Product: CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC

Procedure:
In accordance with (1--1) and (1-2) of Example 1, using eicosanyl bromide and undecenylmagnesium bromide as the raw material, a similar reaction was carried out to obtain hentriacontane as the intermediate product and then by another reaction 1,1,1-trichlorodotriacontane was obtained. One gram of the thus obtained, 1,1,1-trichlorodotriacontane dissolved in 6 ml of n-butyl alcohol was placed in a 50-ml conical flask and 1.4 ml of distilled water and 2.5 g of potassium hydroxide were added to the solution in the flask. The mixture was heated to a temperature of 60° C. to make reaction for 30 hours under agitation. Then, iced water was added to the reaction mixture to cool the mixture, and after neutralizing with an aqueous dilute hydrochloric acid, the separated precipitate was collected by filtration and dried to obtain 0.82 g of the product. After recrystallizing from benzene, 0.52 g of dotriacontanoic acid melting at 95.5° C. was obtained with a yield of 60%.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:13][C:12]3=[O:25])[CH:9]=2)[C:4]2[CH2:26][CH2:27][N:28](C(OC(C)(C)C)=O)[CH2:29][C:3]1=2.C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:49].Cl>>[ClH:49].[ClH:49].[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:13][C:12]3=[O:25])[CH:9]=2)[C:4]2[CH2:26][CH2:27][NH:28][CH2:29][C:3]1=2
Reactant: Cn1c2c(c3ccc(-n4ccc(CCc5ccccc5)cc4=O)cc31)CCN(C(=O)OC(C)(C)C)C2
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Product: Cn1c2c(c3ccc(-n4ccc(CCc5ccccc5)cc4=O)cc31)CCNC2
Yield: 51 %

Procedure:
tert-Butyl 9-methyl-7-(2-oxo-4-phenethylpyridin-1(2H)-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (1.2 g, 2.4 mmol) was deprotected and converted to the dihydrochloride salt according to the procedure of Example 30 (steps e and g) to provide the title compound (550 mg, 51%) as a yellow solid: mp 280-295° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.67 (s, 2H), 7.59-7.52 (m, 3H), 7.35-7.27 (m, 4H), 7.24-7.17 (m, 1H), 7.01 (dd, J=7.4, 2.0 Hz, 1H), 6.38-6.27 (m, 2H), 4.45 (s, 2H), 3.67 (s, 3H), 3.42 (t, J=6.4 Hz, 2H), 2.97-2.89 (m, 4H), 2.81-2.76 (m, 2H); ESI MS m/z 384 [M+H]+; HPLC (Method B)>99% (AUC), tR=13.3 min.
Reaction SMILES: [OH:1][C:2]([CH:4]([C:6]1[CH:15]=[CH:14][C:9]([CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:8][CH:7]=1)[CH3:5])=[O:3].O.[CH2:17]([NH:25][CH2:26][C@@H:27]([C@H:29]([C@@H:31]([C@@H:33]([CH2:35][OH:36])[OH:34])[OH:32])[OH:30])[OH:28])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>C1(C)C=CC=CC=1>[CH2:17]([NH:25][CH2:26][C@@H:27]([C@H:29]([C@@H:31]([C@@H:33]([CH2:35][OH:36])[OH:34])[OH:32])[OH:30])[OH:28])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[OH:3][C:2]([C@H:4]([C:6]1[CH:7]=[CH:8][C:9]([CH2:10][CH:11]([CH3:12])[CH3:13])=[CH:14][CH:15]=1)[CH3:5])=[O:1]
Reactant: CC(C)Cc1ccc(C(C)C(=O)O)cc1
Agent: CCCCCCCCNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)Cc1ccc([C@H](C)C(=O)O)cc1
Temperature: 75 °C

Procedure:
Initial resolution. Racemic ibuprofen (18 g, 87 mmol) was dissolved in toluene (150 mL), and water (0.5 mL) and N-octyl-D-glucamine (12.12 g, 41 mmol) were added to the solution. The mixture was heated slowly to 75° C., forming a clear solution, and the solution then cooled to 20° C. over 3 hours. The resulting precipitate was recovered by filtration, washed with toluene (50 mL), and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (14.75 g, 30 mmol, MR=136.5°~137° C., [α]D =-11.2° (c=0.1, MeOH), 99% ee). The toluene liquors were saved for racemization and recycle of the contained (R)-ibuprofen.
Reaction SMILES: Cl.C[N:3]([C:10]1[CH:15]=[N:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][N:11]=1)[C@H:4]1[CH2:8][CH2:7][CH2:6][C@@H:5]1[NH2:9].[N:20]1[CH:25]=[CH:24][CH:23]=[N:22][C:21]=1[C:26]1[C:27]([C:32]([OH:34])=O)=[N:28][CH:29]=[CH:30][CH:31]=1.N1C2[C:38](=NC=CC=2)N(O)N=1.C(Cl)CCl.C(N(CC)CC)C>C(Cl)Cl>[CH3:38][C:15]1[C:10]([NH:3][C@H:4]2[CH2:8][CH2:7][CH2:6][C@@H:5]2[NH:9][C:32]([C:27]2[C:26]([C:21]3[N:22]=[CH:23][CH:24]=[CH:25][N:20]=3)=[CH:31][CH:30]=[CH:29][N:28]=2)=[O:34])=[N:11][CH:12]=[C:13]([C:16]([F:17])([F:18])[F:19])[N:14]=1
Reactant: CN(c1cnc(C(F)(F)F)cn1)[C@H]1CCC[C@@H]1N
Reactant: O=C(O)c1ncccc1-c1ncccn1
Reactant: On1nnc2cccnc21
Agent: Cl
Solvent: ClCCl
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: Cc1nc(C(F)(F)F)cnc1N[C@H]1CCC[C@@H]1NC(=O)c1ncccc1-c1ncccn1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of (1S,2S)-1-N-methyl-1-N-[5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 23; 100 mg, 0.34 mmol) in DCM (1.2 ml) was added 3-(pyrimidin-2-yl)pyridine-2-carboxylic acid (CAS number 1228431-21-7; 81 mg, 0.40 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (69 mg, 0.51 mmol), EDC (97 mg, 0.51 mmol) and triethylamine (0.14 ml, 1.01 mmol). The reaction was stirred at room temperature for 18 hours and then partitioned between water and DCM, passing through a hydrophobic frit. The organics were concentrated in vacuo and then purified by column chromatography (0-100% ethyl acetate/petrol) to afford the title compound.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([CH2:11][CH3:12])=[CH:5][C:6]=1[C:7]([O:9]C)=O.ClC(Cl)(O[C:17](=[O:23])OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[C:32]1([CH2:38][CH2:39][CH2:40][NH2:41])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(Cl)Cl>[CH2:11]([C:4]1[S:3][C:2]2[NH:1][C:17](=[O:23])[N:41]([CH2:40][CH2:39][CH2:38][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:7](=[O:9])[C:6]=2[CH:5]=1)[CH3:12]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: NCCCc1ccccc1
Reactant: CCc1cc(C(=O)OC)c(N)s1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCc1cc2c(=O)n(CCCc3ccccc3)c(=O)[nH]c2s1
Temperature: 25 °C
Reaction time: 2 h
Yield: 238.9 %

Procedure:
To a solution (40 mL) of methyl 2-amino-5-ethylthiophene-3-carboxylate (0.5 g) in methylene chloride were added triphosgene (0.32 g) and triethylamine (0.59 mL), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added 3-phenylpropan-1-amine (1 g), and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in methanol (20 mL), sodium methoxide (28% methanol solution, 1.3 g) was added, and the mixture was stirred at 60° C. for 2 hr. The reaction mixture was neutralized with hydrochloric acid (10% methanol solution), insoluble material was filtered off, and the solvent was evaporated under reduced pressure. The precipitated solid was collected by filtration to give the title compound as a colorless solid (0.81 g, 95%).
Reaction SMILES: O[C:2]1([C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=2)[CH2:5][O:4][CH2:3]1.C(N(S(F)(F)[F:20])CC)C.[OH-].[Na+]>ClCCl.O>[F:20][C:2]1([C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=2)[CH2:5][O:4][CH2:3]1
Reactant: N#Cc1ccc(C2(O)COC2)cc1
Reactant: CCN(CC)S(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: N#Cc1ccc(C2(F)COC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 4-(3-hydroxyoxetan-3-yl)benzonitrile (Step 1, 600 mg, 3.43 mmol) in dichloromethane (55 mL) was added dropwise N-ethyl-N-(trifluoro-λ4-sulfanyl)ethanamine (662 mg, 4.11 mmol, dissolved in 5 mL dichloromethane) at a temperature of −78° C. After 30 minutes at this temperature, the reaction mixture was rapidly warmed to −20° C. by the aid of a water/ice bath for no longer than 30 seconds whereupon NaOH (1N aq., 20 mL) was added and the reaction mixture was allowed to warm to rt. The mixture was diluted with water (150 mL) and extracted with diethyl ether (3×50 mL). The organic extract was dried with anhydrous magnesium sulfate and filtered. After evaporation of the solvent, the crude product was purified by MPLC (silica, cyclohexane/ethyl acetate 8:1) to afford the title compound in pure form (495 mg, 82%): 1H NMR (400 MHz, CDCl3) δ 7.76 (d, 2H), 7.73 (d, 2H), 5.15 (dd, 2H), 4.81 (dd, 2H); ES-MS m/z 178 (MH)+; HPLC RT (Method F) 1.59 min.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]1([CH2:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][N:19](CCO)[CH2:18][CH2:17]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32](Cl)[C:33]2[S:34][CH:35]=[CH:36][C:37]=2[CH3:38])=[CH:28][CH:27]=1.C(O)(=O)/C=[CH:42]\[C:43](O)=[O:44]>CC(C)=O.C1(C)C=CC=CC=1.C(#N)C>[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]([C:33]2[S:34][CH:35]=[CH:36][C:37]=2[CH3:38])[O:44][CH2:43][CH2:42][CH:18]2[CH2:17][N:16]([CH2:15][CH2:14][CH2:13][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH2:21][CH2:20][NH:19]2)=[CH:28][CH:27]=1
Reactant: Cc1ccsc1C(Cl)c1ccc(F)cc1
Reactant: OCCN1CCN(CCCc2ccccc2)CC1
Reactant: O=C(O)/C=C\C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CC(C)=O
Solvent: CC#N
Product: Cc1ccsc1C(OCCC1CN(CCCc2ccccc2)CCN1)c1ccc(F)cc1

Procedure:
3.0 g (0.022 mol) potassium carbonate were added to a stirred solution of 1.5 g (0.006 mol) 4-(3-phenylpropyl)-1-piperazineethanol (GB Pat. No. 1545094) and 2.41 g (0.010 mol) (4-fluorophenyl)(3-methyl-2-thienyl)methyl chloride (e.g. German patent appl. DE 3726068) in 50 ml acetone. The mixture was refluxed for 2 h, then cooled and diluted with toluene (100 ml). The solution was washed twice with water and once with brine. Evaporation of the organic layer in vacuo yielded an oil, which was redissolved in 50 ml acetonitrile and treated with a solution of maleic acid in acetonitrile. The precipitate was filtered off, washed with diethylether and dried. Recrystallization from ethanol gave 2.88 g (70% of theoretical yield) of the title compound as the dimaleate salt, white solid, m.p. 146°-47° C.
Reaction SMILES: Br[C:2](Cl)(Cl)[C:3]([Br:6])(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:28][C:29]([F:44])([F:43])[C:30]1[CH:31]=[C:32]([C@H](O)C)[CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1.CCCCCC>C1(C)C=CC=CC=1>[Br:6][C@H:3]([C:32]1[CH:33]=[C:34]([C:36]([F:39])([F:37])[F:38])[CH:35]=[C:30]([C:29]([F:28])([F:44])[F:43])[CH:31]=1)[CH3:2]
Reactant: C[C@@H](O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: ClC(Cl)(Br)C(Cl)(Cl)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: C[C@H](Br)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87.5 %

Procedure:
Under an argon atmosphere, 1,2-dibromo-1,1,2,2-tetrachloroethane (7.57 g, 23.2 mmol) was dissolved in toluene (12.5 mL), the solution was added with triphenylphosphine (6.1 g, 23.2 mmol) at 0° C., and the mixture was stirred for 30 minutes. The reaction mixture was added dropwise with a solution of (R)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol (5.0 g, 19.4 mmol, >99.5% ee) in toluene (12.5 mL) at 0° C. over 10 minutes or more, and then the mixture was warmed to room temperature, and stirred at the same temperature for 1 hour. The reaction mixture was added with n-hexane (25 mL), and the mixture was filtered through Celite. The filtrate was washed successively with water, saturated aqueous sodium hydrogencarbonate, and saturated brine, dried over sodium sulfate, and evaporated under reduced pressure. The resulting residue was distilled under reduced pressure (56° C., 0.7 mmHg) to obtain 5.45 g of (S)-1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane as colorless oil.
Reaction SMILES: [CH3:1][N:2]1[CH2:8][CH:7]([OH:9])[C:6]2[CH:10]=[CH:11][S:12][C:5]=2[CH2:4][CH2:3]1.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16](F)[C:15]=1[C:21]([F:24])([F:23])[F:22]>>[Cl:13][C:14]1[C:15]([C:21]([F:22])([F:23])[F:24])=[C:16]([O:9][CH:7]2[CH2:8][N:2]([CH3:1])[CH2:3][CH2:4][C:5]3[S:12][CH:11]=[CH:10][C:6]2=3)[CH:17]=[CH:18][CH:19]=1
Reactant: Fc1cccc(Cl)c1C(F)(F)F
Reactant: CN1CCc2sccc2C(O)C1
Product: CN1CCc2sccc2C(Oc2cccc(Cl)c2C(F)(F)F)C1

Procedure:
The same method as in Example 1 was conducted using 6-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepin-4-ol (Reference Example 28) instead of 6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-4-ol (Reference Example 6) and was conducted using 2-chloro-6-fluorobenzotrifluoride instead of 1-fluoronaphthalene to give the objective compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:15][S:16](Cl)(=[O:18])=[O:17]>CC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([O:8][S:16]([CH3:15])(=[O:18])=[O:17])[CH:5]=[N:6][CH:7]=1
Reactant: Oc1cncc(Br)c1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CS(=O)(=O)Oc1cncc(Br)c1
Reaction time: 2 h

Procedure:
A flask is charged with 5-bromo-pyridin-3-ol (0.200 g, 1.126 mmol), potassium carbonate (0.212 g, 1.487 mmol) and acetone (3 mL). Methanesulfonyl chloride (0.143 g, 1.239 mmol) is then added dropwise. After 2 h, an other portion of methanesulfonyl chloride (0.071 g, 0.61 mmol) is added. After overnight stirring, the suspension is concentrated, diluted with ethyl acetate and filtered through a pad of silica gel. The filtrate is concentrated in vacuo to give a residue, which is purified by silica gel flash chromatography (heptane-ethyl acetate, 4:1 to 7:3) to give a mixture of product and starting material. The fractions are combined, washed three times with saturated aqueous sodium bicarbonate and dried over MgSO4. Concentration in vacuo gives methanesulfonic acid 5-bromo-pyridin-3-yl ester as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 3.25 (s, 3H), 7.86 (m, 1H), 8.52 (d, J=2.3 Hz, 1H), 8.67 (d, J=1.8 Hz, 1H).
Reaction SMILES: O1C=C[CH2:4][CH2:3][CH2:2]1.Cl.[N:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:14]([Li])CCC>C(Cl)Cl.O1CCCC1>[CH:3]([NH:8][CH:13]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:14]1)([CH3:4])[CH3:2]
Reactant: [Li]CCCC
Reactant: C1=COCCC1
Reactant: c1ccncc1
Agent: Cl
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(C)NC1CCCCC1

Procedure:
Refer to Chart 0. The formula-CXIX 2-phenyl selenidyl compound is first prepared. The starting material is the methyl ester of (5E)-6a-carba-PGI2 (Example 23, 0.4 g.) which is converted to the formula-CXVIII bis(tetrahydropyran-2-yl ether) by reaction with dihydropyran in methylene chloride in the presence of pyridine hydrochloride following the procedure of Example 39-II. A solution of that bis(THP) methyl ester in 5 ml. of tetrahydrofuran is added dropwise to the amide formed from N-isopropylcyclohexylamine (0.3 g.) and n-butyllithium (equivalent 1.6 M hexane solution) in tetrahydrofuran (7 ml.) cooled to -78° C. The mixture is stirred at -78° C. for 45 min. and then phenylselenyl chloride is added in tetrahydrofuran solution over a 7 minute period. The mixture is stirred at -78° C. for an additional hour, then poured into 30 ml. of saturated ammonium chloride-ice-water mixture and extracted with diethyl ether. The organic phase is dried and concentrated. The residue is chromatographed on silica gel, eluting with ethyl acetate-toluene (1:8) to give the formula-CXIX compound.
Reaction SMILES: Cl[Si:2]([CH3:5])([CH3:4])[CH3:3].[C:6]([CH2:9][C:10](=[O:12])[CH3:11])(=[O:8])[CH3:7].CN1C=CN=C1>>[CH3:3][Si:2]([CH3:5])([CH3:4])[O:12][C:10]([CH3:11])=[CH:9][C:6](=[O:8])[CH3:7]
Reactant: CC(=O)CC(C)=O
Reactant: C[Si](C)(C)Cl
Agent: Cn1ccnc1
Product: CC(=O)C=C(C)O[Si](C)(C)C
Temperature: 0 °C
Yield: 81.4 %

Procedure:
5.97 g (55.0 mmol) of chlorotrimethylsilane were added dropwise to a solution of 5.00 g (49.9 mmol) of acetylacetone and 4.50 g (55.0 mmol) of 1-methylimidazole while stirring at 0° C. The reaction mixture was stirred for another 1 hour at 0° C. and for 5 minutes at 80° C., resulting in the formation of a liquid two-phase mixture. The upper phase was separated off to give 7.00 g (theory: 8.60 g) of 4-trimethylsilyloxypent-3-en-2-one as a light-yellow, turbid oil having a purity of 84% (GC).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[N:3]=1.O.[NH2:26][NH2:27]>CCO>[NH2:13][C:12]1[C:11]2[C:10](=[CH:9][C:8]([C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([NH:17][CH2:18][CH:19]4[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]4)[CH:5]=3)=[CH:15][CH:14]=2)[NH:27][N:26]=1
Reactant: NN
Reactant: N#Cc1ccc(-c2cc(NCC3CCCCC3)nc(N)n2)cc1F
Solvent: CCO
Solvent: O
Product: Nc1nc(NCC2CCCCC2)cc(-c2ccc3c(N)n[nH]c3c2)n1
Temperature: 120 °C
Reaction time: 1 h
Yield: 51.5 %

Procedure:
To a solution of 4-{2-amino-6-[(cyclohexylmethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile (300 mg, 0.92 mmol) in EtOH (2 mL) was added hydrazine monohydrate (3.0 mL, 61.2 mmol), and the resulting suspension was stirred at 120° C. for 1 hour under microwave conditions. The clear reaction mixture was concentrated, and the resulting residue was purified by RPHPLC (CH3CN/H2O w/0.1% THF) to afford the title compound (160 mg, 48%) as a light yellow solid. LC-MS (ES) m/z=338 [M+H]+. 1HNMR (400 MHz, DMSO-d6): δ 0.92 (m, 2H), 1.19 (m, 3H), 1.51 (m, 1H), 1.68 (m, 5H), 3.14 (s, 2H), 5.37 (s, 2H), 5.95 (s, 2H), 6.29 (s, 1H), 6.85 (bs, 1H), 7.40 (bs, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.83 (s, 1H), 11.5 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:24]=[CH:25]/[CH:26]=O)=[CH:4][N:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:42]([NH:44][CH2:45][CH3:46])[CH3:43]>C(O)(=O)C.ClCCCl>[CH2:42]([N:44]([CH2:45][CH3:46])[CH2:26]/[CH:25]=[CH:24]/[C:5]1[C:6]2[S:10][CH:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:15][CH:16]=3)[C:7]=2[C:2]([NH2:1])=[N:3][CH:4]=1)[CH3:43]
Reactant: Nc1ncc(/C=C/C=O)c2scc(-c3ccc(Oc4ccccc4)cc3)c12
Reactant: CCNCC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: CCN(CC)C/C=C/c1cnc(N)c2c(-c3ccc(Oc4ccccc4)cc3)csc12

Procedure:
A mixture of Example 360B (30 mg, 0.080 mmol), sodium triacetoxyborohydride (35 mg, 0.16 mmol), 1 drop of acetic acid, and diethylamine (12 mg, 0.166 mmol) in 1,2-dichloroethane (2 mL) was stirred for 2 hours at ambient temperature. The mixture was concentrated and the residue was purified by reverse phase chromatography followed by lyophilization to provide the desired product as the acetate salt. 1H NMR (DMSO-d6, 400 MHz) δ 7.94 (s, 1H), 7.55 (s, 1H), 7.44 (m, 4H), 7.20 (t, 1H), 7.11 (m, 4H), 6.67 (d, 1H), 6.22 (m, 1H), 5.55 (br s, 2H), 3.28 (d, 2H), 2.52 (q, 4H), 1.87 (s, 3H), 1.00 (t, 6H); MS m/e 430.4 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[CH:8][NH:9]2)=[CH:5][CH:4]=1.Br[CH2:13][CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].[H-].[Na+]>CN(C=O)C>[Si:16]([O:15][CH2:14][CH2:13][N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=2)[CH:7]=[CH:8]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]
Reactant: COc1ccc2cc[nH]c2c1
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc2ccn(CCO[Si](C)(C)C(C)(C)C)c2c1
Reaction time: 1 h
Yield: 101.8 %

Procedure:
To a solution of 6-methoxy-1H-indole (7.0 g, 47.6 mmol) and (2-bromoethoxy)-tert-butyldimethylsilane (10.7 mL, 50.0 mmol) in DMF (100 mL) under nitrogen was added, portionwise, sodium hydride (65% dispersion in oil) (2.8 g, 71.4 mmol) at room temperature. The reaction mixture was stirred for 1 h, quenched with saturated aq NaHCO3 (100 mL) and diluted with EtOAc (150 mL). The organic phase was washed with water (3×150 mL), saturated aq NaHCO3 (100 mL), brine (2×100 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (SiO2, 10% EtOAc/hexanes) gave the title compound (14.8 g, 98%) as a colorless oil. 1H NMR (300 MHz, CDCl3) 7.62 (d, J=7.2 Hz, 1H), 7.38 (s, 1H), 7.12 (d, J=3.1 Hz, 1H), 6.87 (d, J=7.2 Hz, 1H), 6.52 (d, J=3.1 Hz, 1H), 4.28 (m, 2H), 4.02 (m, 2H), 3.96 (s, 3H), 0.98 (s, 9H), 0.02 (s, 6H).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]([CH:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH3:18])([CH3:17])[CH2:9][CH2:8]1)=[O:6].[CH3:19]I.CO>O1CCCC1.O>[CH3:3][O:4][C:5]([C:7]1([CH3:19])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH3:18])([CH3:17])[CH2:9][CH2:8]1)=[O:6]
Reactant: CI
Reactant: COC(=O)C1CCC(C)(C)c2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: COC(=O)C1(C)CCC(C)(C)c2ccccc21

Procedure:
5.7 g of sodium hydride are placed in 80 ml of absolute tetrahydrofuran in a 500 ml flask provided with a thermometer, stirrer, reflux condenser and dropping funnel and 43.6 g of 1,1-dimethyl-tetralin-4-carboxylic acid methyl ester are added dropwise thereto. The mixture is then heated at reflux temperature for 1 hour. After cooling, 34 g of methyl iodide in 80 ml of absolute tetrahydrofuran are added dropwise and the mixture is held at reflux temperature for a further 1 hour. After cooling, a small amount of methanol is added, the mixture is poured into water and extracted with ether. The ether extracts are washed neutral, dried and evaporated. Distillation gives a quantitative yield of 1,1,4-trimethyl-tetralin-4-carboxylic acid methyl ester of boiling point 102° C./1.5 mmHg; nD20 =1.5219. Odour: tobacco, similar to (3).
Reaction SMILES: Cl.[CH2:2]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH2:5][C@@H:4]([CH2:15][C:16]([OH:18])=[O:17])[NH:3]1.C(N(CC)CC)C.[C:26](=[S:28])=[S:27].[CH3:29]I>CS(C)=O>[CH3:29][S:27][C:26]([N:3]1[C@H:4]([CH2:15][C:16]([OH:18])=[O:17])[CH2:5][C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[NH:13][C:14]=2[CH2:2]1)=[S:28]
Reactant: CI
Reactant: S=C=S
Reactant: O=C(O)C[C@@H]1Cc2c([nH]c3ccccc23)CN1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CSC(=S)N1Cc2[nH]c3ccccc3c2C[C@H]1CC(=O)O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
235 mg of (3S)-1,2,3,4-tetrahydro-β-carboline-3-acetic acid hydrochloride are dissolved in 2 ml of dimethylsulfoxide. 0.42 ml of triethylamine and 0.07 ml of carbon disulfide are added to the mixture, and the mixture is stirred at room temperature for 30 minutes. Then, 0.07 ml of methyl iodide are added dropwise to the mixture. The mixture is further stirred at the same temperature for 2 hours. The reaction mixture is evaporated to remove the solvent, and the residue is dissolved in water. The aqueous solution is acidified with 5% HCl, and extracted with ethyl acetate. The extract is washed with water, dried and then evaporated to remove the solvent. Aqueous ethanol is added to the residue, and the precipitates are collected. 102 mg of (3S)-2-(methylthio)thiocarbonyl-1,2,3,4-tetrahydro-β-carboline-3-acetic acid are obtained as white powder.