Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:3]([NH:12][CH:13]([C:17]2[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][CH:18]=2)[CH2:14][CH2:15][CH3:16])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl.[CH2:27]([O:29][C:30](=[O:34])[CH2:31][CH2:32][NH2:33])C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:1][C:2]1[C:3]([NH:12][CH:13]([C:17]2[CH:18]=[CH:19][C:20]([C:21]([NH:33][CH2:32][CH2:31][C:30]([O:29][CH3:27])=[O:34])=[O:22])=[CH:24][CH:25]=2)[CH2:14][CH2:15][CH3:16])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: CCOC(=O)CCN
Reactant: CCCC(Nc1nc2ccccc2cc1C)c1ccc(C(=O)O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCC(Nc1nc2ccccc2cc1C)c1ccc(C(=O)NCCC(=O)OC)cc1
Temperature: 25 °C
Reaction time: 10 h

Procedure:
Intermediate 5 (31.64 g, 94.61 mmol), β-alanine ethyl ester hydrochloride (45.9 g, 284 mmol), and 1-hydroxybenzotriazole hydrate (80%, 20 wt % water, 47.9 g, 284 mmol) were suspended in dichloromethane (946 mL). Triethylamine (119 mL, 852 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (46.0 g, 237 mmol) were added, and the solution was stirred at room temperature for 10 h. The reaction mixture was washed with water (3×900 mL), then sat. aq NaCl (300 mL). The organic layer was dried over Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure. Purification by silica gel flash chromatography (ethyl acetate/heptane) followed by chiral SFC (Chiralpak AD-H column, 30×250, 20% methanol/carbon dioxide eluent, 0.2% isopropylamine modifier) gave methyl (+)-3-(4-(1-((3-methylquinolin-2-yl)amino)butyl)benzamido)propanoate (Intermediate 6, analytical chiral SFC 4.6 min retention) and methyl (−)-3-(4-(1-((3-methylquinolin-2-yl)amino)butyl)benzamido)propanoate (Intermediate 7, analytical chiral SFC 6.5 min retention)—note that ethyl ester was converted to methyl ester during the reaction and/or purification sequence. 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J=8.4 Hz, 2H), 7.64-7.58 (m, 2 H), 7.55-7.48 (m, 3 H), 7.44 (t, J=7.7 Hz, 1 H), 7.16 (t, J=7.4 Hz, 1 H), 6.76 (t, J=5.5 Hz, 1 H), 5.48 (q, J=7.2 Hz, 1 H), 4.78 (d, J=7.0 Hz, 1 H), 3.76 (q, J=6.0 Hz, 2 H), 3.70 (s, 3 H), 2.64 (t, J=5.9 Hz, 2 H), 2.29 (s, 3 H), 2.04-1.82 (m, 2 H), 1.52-1.29 (m, 2 H), 0.98 (t, J=7.3 Hz, 3 H).
Reaction SMILES: [CH3:1][CH:2]1[C:14]2[N:13]3[CH:15]=[CH:16][N:17]=[C:12]3[C:11](=[O:18])[NH:10][C:9]=2[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.[H-].[Na+].C[Si](C)(C)Cl.Cl.Cl[CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1>C(O)(=O)C.CN(C)C=O>[CH3:1][C:2]1([CH2:28][C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)[C:14]2[N:13]3[CH:15]=[CH:16][N:17]=[C:12]3[C:11](=[O:18])[NH:10][C:9]=2[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2
Reactant: ClCc1ccncc1
Reactant: CC1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Agent: C[Si](C)(C)Cl
Agent: Cl
Agent: [H-]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: CC1(Cc2ccncc2)c2ccccc2-c2[nH]c(=O)c3nccn3c21
Temperature: 0 °C
Reaction time: 1 h
Yield: 27.1 %

Procedure:
To a stirred mixture of 0.48 g of 10-methyl-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one, 25 ml of dimethylformamide and 0.33 g of 80% sodium hydride is added 0.3 ml of trimethylchlorosilane at a temperature in the region of 20° C. and under cover of argon. The stirring is continued for one hour, followed by the addition of 0.07 g of 80% sodium hydride and the stirring is continued for 30 minutes. 0.36 g of 4-chloromethylpyridine hydrochloride is then added and the stirring is continued for 20 minutes. 2 ml of acetic acid are added to the reaction mixture, which is poured into 150 ml of ice-water and concentrated on a rotary evaporator. The evaporation residue is treated with 200 ml of ethyl acetate and filtered, and the filtrate is evaporated. The yellow-orange paste obtained is purified by chromatography on a column of silica (30 g), eluting with a mixture of dichloromethane and methanol (95/5 by volume). After trituration in 40 ml of ethyl ether, filtration and drying at 60° C. under vacuum (1 mmHg; 0.13 kPa), 0.18 g of 10-methyl-10-(4-pyridylmethyl)-5H,10H-imidazo-[1,2-a]indeno[1,2-e]pyrazin-4-one is obtained, in the form of a cream-coloured solid melting above 260° C. (Analysis % calculated C: 73.15, H: 4.91, N: 17.06, O: 4.87, % found C: 73.2, H: 5.1, N: 17.0).
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([C:18](F)=[O:19])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]#[N:17])([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][C:24]([C:26]1[N:27]=[C:28]([NH2:31])[S:29][CH:30]=1)=[O:25]>O1CCOCC1>[CH3:22][O:23][C:24]([C:26]1[N:27]=[C:28]([NH:31][C:18](=[O:19])[C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:21])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]#[N:17])[S:29][CH:30]=1)=[O:25]
Reactant: COC(=O)c1csc(N)n1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1C#N)C(=O)F
Solvent: C1COCCO1
Product: COC(=O)c1csc(NC(=O)[C@H](Cc2ccccc2C#N)NC(=O)OC(C)(C)C)n1
Temperature: 120 °C
Yield: 95.3 %

Procedure:
[(S)-2-(2-Cyano-phenyl)-1-fluorocarbonyl-ethyl]-carbamic acid tert-butyl ester (2.4 g, 8.2 mmol) and 2-amino-thiazole-4-carboxylic acid methyl ester (1.24 g, 7.8 mmol) were dissolved in p-dioxane (40 mL). The mixture was heated in a sealed tube under microwave irradiation at 120° C. for 15 minutes The solution was concentrated, and the residue was purified by chromatography over silica gel eluted with 1:1 ethyl acetate/hexanes to give 2-[(S)-2-tert-butoxycarbonylamino-3-(2-cyano-phenyl)-propionylamino]-thiazole-4-carboxylic acid methyl ester as a white solid (3.2 g, 95%).
Reaction SMILES: [CH3:1][CH:2]([CH3:12])[C@H:3]([N:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)[C@H:4](O)[CH3:5].CCN(CC)CC.CS(Cl)(=O)=O.[CH3:25][C:26]([SH:28])=O>C1C=CC=CC=1.O.C(Cl)Cl>[CH3:1][CH:2]([CH3:12])[C@H:3]([N:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)[C@H:4]([C:26](=[S:28])[CH3:25])[CH3:5]
Reactant: CC(C)[C@@H]([C@@H](C)O)N1CCCC1
Reactant: CC(=O)S
Agent: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CC(=S)[C@H](C)[C@H](C(C)C)N1CCCC1
Reaction time: 12 h

Procedure:
To a three-necked flask, compound (6b4a) (0.855 g, 5.0 mmol), CH2Cl2 (20 mL) and NEt3 (1.01 g, 10.0 mmol) are added under nitrogen system. Next, MeSO2Cl (0.69 g, 6.0 mmol, dissolved in 20 mL CH2Cl2) is added dropwisely at 0° C. After complete reaction for 2 hours, a coarse product is obtained through repeated depressing concentration and adding benzene therein. The coarse product is then added into benzene (20 mL) with refluxing, and MeCOSH (0.46 g, 6.0 mmol) and NEt3 (1.01 g, 10.0 mmol) dissolved in 20 mL benzene are injected into the above solution under the nitrogen system. After 12 hours, H2O (20 mL) is added to terminate the reaction. The product is repeatedly extracted with EtOAc (20 mL), wherein the organic phase is dehydrated with Na2SO4. A coarse product is obtained after filtration and concentration. Column chromatography (Silica gel 70 g, eluent is n-Hexane:NEt3=100:1) is used to purify the coarse product and two orange liquids, compound (6b4b) (0.229 g) and compound (2f4b) (0.458 g), are obtained. The yields of compound (6b4b) and compound (2f4b) are 20% and 40%, respectively. The other analysis for compound (6b4b) includes:
Reaction SMILES: C(OC([NH:8][CH2:9][C:10]([NH:12][C:13]1[CH:18]=[C:17]([C:19]2[S:41][C:22]3=[N:23][C:24]([N:28]4[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]4)=[CH:25][C:26](=[O:27])[N:21]3[N:20]=2)[CH:16]=[CH:15][N:14]=1)=[O:11])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][CH2:9][C:10]([NH:12][C:13]1[CH:18]=[C:17]([C:19]2[S:41][C:22]3=[N:23][C:24]([N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[CH:25][C:26](=[O:27])[N:21]3[N:20]=2)[CH:16]=[CH:15][N:14]=1)=[O:11]
Reactant: CC(C)(C)OC(=O)NCC(=O)Nc1cc(-c2nn3c(=O)cc(N4CCN(C(=O)OC(C)(C)C)CC4)nc3s2)ccn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCC(=O)Nc1cc(-c2nn3c(=O)cc(N4CCNCC4)nc3s2)ccn1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of tert-butyl 4-(2-(2-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-4-yl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (50 mg, 0.085 mmol) in DCM (1 ml) is added TFA (0.25 ml) and the mixture is stirred at room temperature for 2 h. The solvent is removed in vacuo and the residue is directly purified through preparative HPLC to give the desired 2-Amino-N-(4-(5-oxo-7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)pyridin-2-yl)acetamide. 1H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 9.10-8.60 (br.s., 2H), 8.61 (d, J=5.1 Hz, 1H), 8.58 (s, 1H), 8.35-8.05 (br.s., 3H), 7.66 (dd, J=5.1, 1.6 Hz, 1H), 5.63 (s, 1H), 3.92 (s, 2H), 3.79 (t, J=4.7 Hz, 4H), 3.19 (t, J=4.7 Hz, 4H); LC/MS: tR=2.163 min; HRMS: m/z (M+H+)=387.1346 (Calculated for C16H19N8O2S=387.1352).
Reaction SMILES: [N:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([O:14][C:15]1[C:24]3[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=3)[N:18]=[CH:17][CH:16]=1)=[CH:9]2)=[C:2]=[S:3].[CH3:29][O:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1>C(Cl)Cl>[CH3:26][O:25][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][C:21]=1[O:27][CH3:28])[N:18]=[CH:17][CH:16]=[C:15]2[O:14][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[C:4]([NH:1][C:2]([NH:35][C:34]1[CH:36]=[CH:37][C:31]([O:30][CH3:29])=[CH:32][CH:33]=1)=[S:3])=[CH:13][CH:12]=[CH:11]2
Reactant: COc1ccc(N)cc1
Reactant: COc1cc2nccc(Oc3ccc4c(N=C=S)cccc4c3)c2cc1OC
Solvent: ClCCl
Product: COc1ccc(NC(=S)Nc2cccc3cc(Oc4ccnc5cc(OC)c(OC)cc45)ccc23)cc1
Reaction time: 14 h

Procedure:
To a solution of 4-(5-isothiocyanatonaphthalen-2-yloxy)-6,7-dimethoxyquinoline (27 mg, 0.070 mmol) in DCM (348 μL) at RT was added 4-methoxyaniline (17.2 mg, 0.140 mmol) in one portion. After stirring for 14 h, the crude mixture was concentrated under reduced pressure and purified by silica gel chromatography. MS (ESI, pos. ion) m/z: 512.1. (M+1). Mass Calc'd for C18H15NO3: 511.60.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C([Li])CCC.[NH:21]1[CH:25]=[C:24]([C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[N:23]=[CH:22]1.[Cl-].[NH4+]>C1COCC1.CCCCCC>[NH:21]1[CH:25]=[C:24]([C:26]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=3)=[CH:4][CH:3]=2)([OH:30])[CH:27]([CH3:29])[CH3:28])[N:23]=[CH:22]1
Reactant: CC(C)C(=O)c1c[nH]cn1
Reactant: COc1ccc(-c2ccc(Br)cc2)cc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1ccc(-c2ccc(C(O)(c3c[nH]cn3)C(C)C)cc2)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 41.2 %

Procedure:
4-Bromo-4′-methoxy-1,1′-biphenyl (1.95 g) was dissolved in THF (40 ml) and the mixture was cooled to −78° C. A solution (1.6 M; 5.5 ml) of n-butyllithium in hexane was added dropwise, and the mixture was stirred at −78° C. for 1 h. Then, a solution (10 ml) of 1-(1H-imidazol-4-yl)-2-methyl-1-propanone (335 mg) in THF was slowly added dropwise. The reaction mixture was heated from −78° C. to room temperature and saturated aqueous ammonium chloride solution was added to the reaction mixture. The mixture was extracted with ethyl acetate and the organic layer was dried and concentrated. The obtained residue was recrystallized from ethyl acetate to give the title compound (322 mg) as a colorless solid.
Reaction SMILES: FC(F)(F)C(O)=O.[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][C:21]1=[O:26])(=[O:19])=[O:18].[CH3:27][O:28][C:29]1[CH:53]=[CH:52][C:32]([CH2:33][O:34][C:35]([NH:37][C:38]2[NH:39][C:40](=[O:51])[C:41]3[N:42]=[CH:43][N:44]([CH2:47][C:48](O)=[O:49])[C:45]=3[N:46]=2)=[O:36])=[CH:31][CH:30]=1>>[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17]([N:20]1[CH2:25][CH2:24][N:23]([C:48](=[O:49])[CH2:47][N:44]2[CH:43]=[N:42][C:41]3[C:40](=[O:51])[NH:39][C:38]([NH:37][C:35]([O:34][CH2:33][C:32]4[CH:52]=[CH:53][C:29]([O:28][CH3:27])=[CH:30][CH:31]=4)=[O:36])=[N:46][C:45]2=3)[CH2:22][C:21]1=[O:26])(=[O:19])=[O:18]
Reactant: O=C1CNCCN1S(=O)(=O)c1nc2ccccc2s1
Reactant: COc1ccc(COC(=O)Nc2nc3c(ncn3CC(=O)O)c(=O)[nH]2)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(COC(=O)Nc2nc3c(ncn3CC(=O)N3CCN(S(=O)(=O)c4nc5ccccc5s4)C(=O)C3)c(=O)[nH]2)cc1

Procedure:
The title compound was synthesized by the reaction of 1-(benzothiazole-2-sulfonyl)-piperazin-2-one trifluoroacetic acid salt with [2-N-(4-methoxybenzyloxycarbonyl)-guanin-9-yl]-acetic acid as per the procedure of Example 52. 1H NMR (500 MHz; DMSO-d6) δ 11.38 (bs, 2H), 8.33 (m, 1H), 8.24 (m, 1H), 7.81 (d, 0.6H), 7.77 (d, 0.4H), 7.71 (m, 2H), 7.36 (d, 2H), 6.94 (d, 2H), 5.16 (s, 2H), 5.12 (s, 1.2H), 5.02 (s, 0.8H), 4.51 (s, 0.8H), 4.26 (s, 1.2H), 4.24 (t, 1.2H), 4.08 (t, 0.8H), 4.03 (t, 1.2H), 3.85 (t, 0.8H), 3.75 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[C:7]2[CH:8]=[CH:9][N:10]=[CH:11][C:6]=2[C:5]([CH3:12])=[C:4]2[C:13]3[CH:19]=[C:18]([O:20]C)[CH:17]=[CH:16][C:14]=3[NH:15][C:3]=12.Cl.N1C=CC=CC=1>>[CH3:1][C:2]1[C:7]2[CH:8]=[CH:9][N:10]=[CH:11][C:6]=2[C:5]([CH3:12])=[C:4]2[C:13]3[CH:19]=[C:18]([OH:20])[CH:17]=[CH:16][C:14]=3[NH:15][C:3]=12
Reactant: COc1ccc2[nH]c3c(C)c4ccncc4c(C)c3c2c1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1c2ccncc2c(C)c2c1[nH]c1ccc(O)cc12

Procedure:
A mixture of one part by weight 9-methoxy-ellipticine obtained by extraction from "yellowwood" (Ochrosia maculata) from the island of Reunion, and from 3 to 11 parts by weight of pyridine hydrochloride were heated with gentle reflux for 30 to 90 minutes. The reaction mass became a dark brown colour; it was then poured over crushed ice, the precipitate formed was centrifuged and washed several times with iced water and then recrystallized in methanol. The crystals obtained were orange coloured.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)=[N:7][N:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[CH:10][C:9]=12)=[O:4].[OH-].[Na+].Cl>C(O)C>[F:24][C:20]1[CH:19]=[C:18]([C:6]2[C:5]([C:3]([OH:4])=[O:2])=[C:9]3[CH:10]=[CH:11][C:12]([C:14]([F:16])([F:15])[F:17])=[CH:13][N:8]3[N:7]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: COC(=O)c1c(-c2cccc(F)c2)nn2cc(C(F)(F)F)ccc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1c(-c2cccc(F)c2)nn2cc(C(F)(F)F)ccc12
Yield: 93.8 %

Procedure:
To a suspension of 2-(3-fluoro-phenyl)-6-trifluoromethyl-pyrazolo[1,5-a]pyridine-3-carboxylic acid methyl ester (448 mg) in ethanol (10 ml) was added 2N sodium hydroxide and heated at reflux for 3 h. The cooled reaction mixture was acidified with 2N hydrochloric acid and the resulting solid isolated by filtration and dried in vacuo at 60° to give the title compound as an off-white solid (403 mg, 93%).
Reaction SMILES: CN(CCN(C)C)C.[Li]CCCC.[CH3:14][S:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1.CN([CH:25]=[O:26])C.C(=O)(O)[O-].[Na+]>C(OCC)C>[CH3:14][S:15][C:16]1[C:17]([CH:25]=[O:26])=[N:18][CH:19]=[CH:20][CH:21]=1
Reactant: CSc1cccnc1
Reactant: CN(C)C=O
Agent: CN(C)CCN(C)C
Agent: O=C([O-])O
Agent: [Li]CCCC
Solvent: CCOCC
Product: CSc1cccnc1C=O
Temperature: -78 °C
Reaction time: 2 h
Yield: 19.4 %

Procedure:
To a cold (−78° C.) stirred solution of TMEDA (0.60 mL, 4.0 mmol) in dry diethyl ether (15 mL) was added a 2.5 M solution of nBuLi in hexanes (1.6 mL, 4.0 mmol). The resulting mixture was stirred 30 min at −78° C., at which point a solution of 3-(methylthio)pyridine (prepared as described by Trecourt, F.; Breton, G.; Bonnet, V.; Mongin, F.; Marsais, F.; Queguiner, G. Tetrahedron 2000, 56, 1349-1360) (500 mg, 4.0 mmol) in dry diethyl ether (5 mL) was added dropwise. The resulting red/orange solution was stirred 2 h at −78° C., then neat DMF (0.31 mL, 4.4 mmol) was added dropwise and stirring was continued for a further 2 h. Saturated aqueous sodium bicarbonate (20 mL) was added, then the phases were separated and the aqueous layer was extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (MgSO4), and concentrated in vacuo. Purification of the crude material thus obtained by flash chromatography (silica gel, 4:1 hexanes-EtOAc) afforded 119 mg (19%) of 3-methylsulfanyl-pyridine-2-carbaldehyde. 1H NMR (CDCl3) □ 2.45 (s, 3H), 7.42 (dd, 1H, J=8, 5 Hz), 7.67 (d, 1H, J=9 Hz), 8.50-8.52 (m, 1H), 10.14 (s, 1H).
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][CH2:9][C@@H:10]([OH:19])[C@@H:11]([OH:18])[C@H:12]([OH:17])[C@H:13]([OH:16])[CH2:14][OH:15])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22]>O>[CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@H:9]2[O:16][C@H:13]([CH2:14][OH:15])[C@@H:12]([OH:17])[C@H:11]([OH:18])[C@H:10]2[OH:19])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22]
Reactant: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Solvent: O
Product: OC[C@H]1O[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 125 °C

Procedure:
Ninety-five parts by weight of high-purity crystalline trehalose hydrate and 18 parts by weight of palatinit were placed in a dissolving tank, and admixed with and dissolved by heating in 63 parts by weight of water. The solution was placed in a concentrator, concentrated to boil down by heating to 125° C. under reduced pressure, continued concentrating by heating under reduced pressure while keeping the temperature until reaching to a moisture content of about 1.0%. Similarly as in Example A-1, the concentrate was subjected to an extruder for forming, cooled to ambient temperature to obtain a short-rod thermoplastic shaped-body of trehalose, about 2 mm in diameter and about 4 mm in length. Since the product was a colorless, transparent or translucent, and substantially amorphous shaped-body having thermoplasticity and satisfactory storage-stability under indoor circumstances, it can be arbitrarily reheated to a temperature of about 90° C. to about 160° C. to impart it free-flowing ability, then transformed or processed into a shaped-body with an appropriate form with or without using other substances having different functions. The product can be also used arbitrarily for preparing a paste containing trehalose by dissolving in a relatively-small amount of hot water, and the resulting paste can be used intact in an amorphous form or used as a powdered base after crystallization of trehalose.
Reaction SMILES: CN(C)[CH:3]=[C:4]1[CH2:9][CH2:8][CH2:7][CH:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]1=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([NH:39][C:40]([NH2:42])=[NH:41])[CH:30]=[CH:31][C:32]=1[N:33]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]1>>[CH3:25][O:26][C:27]1[CH:28]=[C:29]([NH:39][C:40]2[N:42]=[CH:3][C:4]3[CH2:9][CH2:8][CH2:7][CH:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]=3[N:41]=2)[CH:30]=[CH:31][C:32]=1[N:33]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]1
Reactant: CCOC(=O)C1CCCC(=CN(C)C)C1=O
Reactant: COc1cc(NC(=N)N)ccc1-n1cnc(C)c1
Solvent: O=[N+]([O-])O
Product: CCOC(=O)C1CCCc2cnc(Nc3ccc(-n4cnc(C)c4)c(OC)c3)nc21

Procedure:
The title compound was prepared from ethyl 3-[1-dimethylamino-methylidene]-2-oxo-cyclohexanecarboxylate (49 mg, 0.22 mmol) and N-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-guanidine dinitrate (55 mg, 0.15 mmol) using in analogous manner the procedure described in example 45b). Obtained as a pale-yellow solid (8 mg, 10%). MS ISP (m/e): 408.4 [(M+H)+]. mp 162-164° C.
Reaction SMILES: [CH:1]([N:3]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[CH:16][CH:15]=3)=[CH:13][C:8]=2[CH:7]=[C:6]([C:24](O)=[O:25])[CH2:5][CH2:4]1)=[O:2].S(Cl)(Cl)=O.[CH3:31][N:32]([CH:34]=O)[CH3:33]>>[CH:1]([N:3]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[CH:16][CH:15]=3)=[CH:13][C:8]=2[CH:7]=[C:6]([C:24]([NH:3][C:9]2[CH:10]=[CH:11][C:12]([CH2:34][N:32]([CH3:31])[CH:33]3[CH2:22][CH2:21][O:20][CH2:17][CH2:16]3)=[CH:13][CH:8]=2)=[O:25])[CH2:5][CH2:4]1)=[O:2]
Reactant: CN(C)C=O
Reactant: CCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3C=O)cc1
Solvent: O=S(Cl)Cl
Product: CCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3C=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81 %

Procedure:
In DMF (10.0 ml) was suspended 1-formyl-7-(4-propoxyphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (433 mg). To the suspension was added thionyl chloride (0.22 ml), and the mixture was stirred at room temperature for 30 minutes. Under reduced pressure, the solvent was evaporated, and to the mixture was added THF (15.0 ml). On the other hand, to 4-[[N-methyl-N-tetrahydro-2H-pyran-4-yl)amino]methyl]aniline dihydrochloride (434 mg) was added THF (10.0 ml) and then added triethylamine (1.29 ml). The previously prepared acid chloride suspension was added dropwise at 0° C. The mixture was stirred at room temperature for 4 hours. To the mixture was added water, and the mixture was washed with water and saturated brine, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was recrystallized from ethanol to give 1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-(4-propoxyphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide (554 mg, 81%) as white crystals.
Reaction SMILES: [C:1]([C:3](=[C:8]([C:10]1[CH:15]=[C:14]([F:16])[C:13]([F:17])=[CH:12][C:11]=1[Cl:18])[OH:9])[C:4]([O:6][CH3:7])=[O:5])#[N:2]>CO.[Ni]>[NH2:2][CH:1]=[C:3]([C:8](=[O:9])[C:10]1[CH:15]=[C:14]([F:16])[C:13]([F:17])=[CH:12][C:11]=1[Cl:18])[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)C(C#N)=C(O)c1cc(F)c(F)cc1Cl
Agent: [Ni]
Solvent: CO
Product: COC(=O)C(=CN)C(=O)c1cc(F)c(F)cc1Cl
Reaction time: 4 h

Procedure:
1.0 g of the product from Example 2 was dissolved in methanol, 0.5 g of Raney nickel was added and hydrogenation was carried out under normal pressure at room temperature for four hours. The catalyst was separated off, the solution which remained was evaporated and the evaporation residue was recrystallized from i-propanol.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)=[O:8].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N:31]2[CH2:36][CH2:35][N:34]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([NH:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[O:8])[CH2:33][CH2:32]2)=[CH:23][CH:24]=1
Reactant: O=C(CCCCCBr)NCc1ccccn1
Reactant: COc1ccc(-c2ccccc2N2CCNCC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1ccc(-c2ccccc2N2CCN(CCCCCC(=O)NCc3ccccn3)CC2)cc1
Yield: 60 %

Procedure:
A stirred mixture of 6-bromo-N-(2-pyridylmethyl)hexanamide (0.60 g, 2.1 mmol), 1-[2-(4-methoxyphenyl)phenyl]piperazine (0.68 g, 2.5 mmol) and K2CO3 (3.5 mmol) in acetonitrile was refluxed overnight. After cooling, the mixture was evaporated to dryness and H2O (20 mL) was added to the residue. The aqueous phase was extracted with AcOEt (2×30 mL). The collected organic layers were dried over Na2SO4 and evaporated under reduced pressure. The crude residue was chromatographed (CHCl3/MeOH, 19:1, as eluent) to afford pure compound in 60% yield. 1H NMR (CDCl3): δ 1.35-1.42 (m, 2H), 1.53-1.63 (m, 2H), 1.68-1.78 (m, 2H), 2.28 (t, 2H, J=7.4 Hz), 2.42 (app. t, 2H), 2.65 (br s, 4H), 3.09 (br s, 4H), 3.81 (s, 3H), 4.45 (d, 2H, J=6.1 Hz), 6.12 (br t, 1H, D2O exchanged), 6.94 (d, 2H, J=8.8 Hz), 7.00 (d, 1H, J=8.0 Hz), 7.09-7.16 (m, 2H), 7.22-7.30 (m, 3H), 7.46 (d, 2H, J=8.8 Hz), 8.58 (m, 1H). GC-MS m/z 473 (M+1, 1), 472 (M+, 5), 379 (20), 282 (50), 226 (100), 210 (35).