Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@@H:15]([CH2:22][CH2:23][CH3:24])[C:16](N(OC)C)=[O:17])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(OCC)(=O)C.CCCCCC>O1CCCC1>[CH2:25]([N:14]([CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C@@H:15]([CH2:22][CH2:23][CH3:24])[CH:16]=[O:17])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: CCC[C@@H](C(=O)N(C)OC)N(Cc1ccccc1)Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCC[C@@H](C=O)N(Cc1ccccc1)Cc1ccccc1
Reaction time: 2 h
Yield: 94.3 %

Procedure:
To anhydrous tetrahydrofuran (1.5 L) previously cooled to −20° C. to −30° C. was added solid lithium aluminum hydride (33.5 g; 0.882 mol; 120 mole %) slowly with stirring. A solution of (S)-2-(dibenzylamino)-N-methoxy-N-methylpentanamide (6) (250 g; 0.735 mol) in anhydrous tetrahydrofuran (1 L) at −30° C. was slowly added to the above mixture under a nitrogen atmosphere. The reaction was continued for 2 hours at −30° C., monitoring progress of the reaction by TLC analysis (ethyl acetate/hexane, 1:9). Upon completion of the reaction, the excess reagent was quenched by the dropwise addition of ethyl acetate (1 L) and ice-cold water (300 ml) at −30° C. The insoluble salts were filtered through celite, the filtrate diluted with water (3 L), and the product extracted into ethyl acetate (2 L). The combined ethyl acetate layers were washed with water (2 L), dried over sodium sulfate, filtered, and solvent removed under reduced pressure to provide (S)-2-(dibenzylamino)pentanal (7) (195 g) as a light yellow oil, which was used without purification in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([S:11]([Cl:14])(=[O:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[C:24]([F:27])([F:26])[F:25])[CH2:19][NH2:20].CCN(CC)CC>C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]([S:11]([Cl:14])(=[O:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([NH:20][CH2:19][C:18]1[CH:21]=[CH:22][C:23]([C:24]([F:25])([F:26])[F:27])=[C:16]([Cl:15])[CH:17]=1)=[O:5]
Reactant: O=C(Cl)c1ccc(S(=O)(=O)Cl)cc1Cl
Reactant: NCc1ccc(C(F)(F)F)c(Cl)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=C(NCc1ccc(C(F)(F)F)c(Cl)c1)c1ccc(S(=O)(=O)Cl)cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 40.7 %

Procedure:
To a solution of 2-chloro-4-(chlorosulfonyl)benzoyl chloride (J. Org. Chem, 56, 16, 1991, 4974) (300 mg, 0.877 mmol, 1 eq) in DCM (3 ml) was added 3-chloro-4-(trifluoromethyl)benzylamine (175 mg, 0.835 mmol, 0.95 eq) and Et3N (33 mg, 0.32 mmol, 0.37 eq) and the reaction mixture stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (10 ml), washed with water (10 ml), dried over sodium sulphate, filtered and evaporated. The crude material was purified by column chromatography eluting with ethyl acetate to yield the title compound (154 mg, 0.34 mmol, 39%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][CH2:24][CH:23]([CH3:27])[CH2:22]4)=[CH:14][CH:13]=3)O)=[C:8]([C:28]3[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=3)[S:7][C:6]=2[CH:35]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH2:10][C:12]3[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][CH2:24][CH:23]([CH3:27])[CH2:22]4)=[CH:16][CH:17]=3)=[C:8]([C:28]3[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=3)[S:7][C:6]=2[CH:35]=1
Reactant: CC1CCCN(CCOc2ccc(C(O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1CCCN(CCOc2ccc(Cc3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 65.5 %

Procedure:
To a suspension of the product of Example 24 (0.466 g, 0.980 mmol) stirring in dichloromethane (24 mL) at 0° C. was added triethylsilane (0.94 mL, 5.8 mmol). After 10 minutes, trifluoroacetic acid (6.4 mL) was added at such a rate that the temperature was maintained below 5° C. The resulting solution was stirred at 0° C. for 2 hours, then quenched by pouring it into a saturated aqueous sodium bicarbonate solution (50 mL). Methanol was added as necessary to dissolve any residue. This mixture was then extracted with ethyl acetate (2×200 mL). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated. Purification by radial chromatography (4 mm, silica gel, 8:2 ethyl acetate/methanol) gave 0.304 g (68%) of the title compound as a white foam: 1H NMR (300 MHz, MeOD-d4) δ7.26-7.30 (m, 3H), 7.18 (d, 1H, J=2.2 Hz), 7.03 (d, 2H, J=8.6 Hz), 6.74-6.83 (m, 5H), 4.07-4.11 (m, 4H), 3.00-3.20 (m, 4H), 2.80-2.85 (m, 1H), 2.35-2.41 (m, 2H), 2.05-2.18 (m, 1H), 1.43-1.48 (m, 1H), 1.06 (t, 3H, J=6.2 Hz); IR (KBr) 3385, 2958, 1677, 1610, 1509, 1239, 837 cm−1; MS (FD) m/z 460 (m+).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=O)[NH:8][C:6](=O)[C:5]2=[CH:11][CH:12]=1.CO.Cl.[OH-].[Na+]>O1CCCC1>[CH3:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:11][CH:12]=1)[CH2:6][NH:8][CH2:9]2
Reactant: Cc1ccc2c(c1)C(=O)NC2=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1ccc2c(c1)CNC2
Temperature: 60 °C
Reaction time: 8 h
Yield: 26.9 %

Procedure:
The 4-methylphthalimide (1.8 g) obtained above was suspended in tetrahydrofuran (3 ml), then 1 N borane tetrahydrofuran complex (30 ml) was added thereto at room temperature and stirred overnight at 60° C. The mixture was cooled to 0° C., then methanol (2.8 ml) and 6 N hydrochloric acid (3.2 ml) were added thereto, and the mixture was refluxed for 1 hour. The reaction mixture was cooled to 0° C., then 6 N sodium hydroxide solution was added thereto, and the reaction solution was extracted with ethyl acetate and then the extract was dried over sodium sulfate anhydrous. The resulting product was concentrated under reduced pressure, and the residue was purified by column chromatography (eluting solvent; dichloromethane→dichloromethane:methanol 10:1→5:1) to give the title compound (400 mg, Y.:27%).
Reaction SMILES: [CH2:1]([CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[NH:5][C:4]1=[O:13])[CH3:2].Br[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][Br:20]>>[Br:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C:3]1([CH2:1][CH3:2])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[NH:5][C:4]1=[O:13]
Reactant: CCC1C(=O)Nc2ccc(F)cc21
Reactant: BrCCCCCBr
Product: CCC1(CCCCCBr)C(=O)Nc2ccc(F)cc21

Procedure:
The title compound is prepared according to process E starting from 3-ethyl-5-fluoro-1,3-dihydro-2H-indol-2-one and 1,5-dibromopentane.
Reaction SMILES: [C:1]1([CH:11]([CH2:16][C:17](O)=[O:18])[CH2:12][C:13]([OH:15])=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(OC(=O)C)(=O)C>C(OC(C)C)(C)C>[C:1]1([CH:11]2[CH2:16][C:17](=[O:18])[O:14][C:13](=[O:15])[CH2:12]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)CC(CC(=O)O)c1cccc2ccccc12
Solvent: CC(=O)OC(C)=O
Solvent: CC(C)OC(C)C
Product: O=C1CC(c2cccc3ccccc23)CC(=O)O1
Temperature: 25 °C

Procedure:
20 g of 3-(1-naphthyl) glutaric acid (0.0774 moles) prepared by the method described by Hey et al [J. Chem. Soc. 1949, 3177-81] were suspended in 400 mL of isopropyl ether. 36.5 mL of acetic anhydride (0.387 moles) were added and the suspension, well agitated, was heated under reflux for three hours. At the end of this time, the mixture was cooled to ambient temperature and the precipitate filtered off and washed well with isopropyl ether. After drying at 60° C. under vacuum, 13.9 g of the product were recovered.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH2:9][CH2:10][N:11]([CH3:17])[CH2:12][CH2:13][CH2:14][CH2:15][NH2:16])=[CH:4][CH:3]=1.[C:24](N1C=CN=C1)(N1C=CN=C1)=[O:25].[NH:36]([C:40]1[S:41][CH:42]=[C:43]([CH2:45][S:46][CH2:47][CH2:48][NH2:49])[N:44]=1)[C:37]([NH2:39])=[NH:38]>C(OCC)(=O)C.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[CH2:9][CH2:10][N:11]([CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:24]([NH:49][CH2:48][CH2:47][S:46][CH2:45][C:43]2[N:44]=[C:40]([NH:36][C:37]([NH2:39])=[NH:38])[S:41][CH:42]=2)=[O:25])[CH3:17])=[CH:6][CH:7]=1
Reactant: N=C(N)Nc1nc(CSCCN)cs1
Reactant: CN(CCCCN)CCC(c1ccc(F)cc1)c1ccccn1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CCOC(C)=O
Solvent: CO
Product: CN(CCCCNC(=O)NCCSCc1csc(NC(=N)N)n1)CCC(c1ccc(F)cc1)c1ccccn1

Procedure:
Preparation is effected analogously to Example 63, using 0.95 g (3.5 mmol) of N-[3-(4-fluorophenyl)-3-(2-pyridyl)propyl]-N-methyl-1,4-butanediamine, an equimolar amount of 1,1'-carbonyldiimidazole and 0.82 g (3.5 mmol) of 2-[[(2-guanidino-4-thiazolyl)methyl]thio]ethaneamine as starting materials. Working up by chromatography (eluant: ethyl acetate/methanol 9+1) analogously to Example 63 yields the purified title compound in the form of a dry foam; MS (+FAB method): m/z (rel. int.[%])=573 ([M+H]+ 2), 214 (100); IR (KBr): 1632 cm-1 (C=O). For analytical purposes a sample is converted into the O,O'-ditoluoyltartaric acid salt and recrystallised from ether/isopropanol; m.p.: from 120° C. with decomposition.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:26])[C:5]([CH3:25])([CH3:24])[CH2:6][CH2:7][CH2:8][CH2:9][C:10](=[O:23])[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:22])([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH3:2].[BH4-].[Na+].O>CO>[CH2:19]([O:18][C:16](=[O:17])[C:15]([CH3:21])([CH3:22])[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]([OH:23])[CH2:9][CH2:8][CH2:7][CH2:6][C:5]([CH3:25])([CH3:24])[C:4]([O:3][CH2:1][CH3:2])=[O:26])[CH3:20]
Reactant: CCOC(=O)C(C)(C)CCCCC(=O)CCCCC(C)(C)C(=O)OCC
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCOC(=O)C(C)(C)CCCCC(O)CCCCC(C)(C)C(=O)OCC
Reaction time: 2 h
Yield: 91.3 %

Procedure:
7-Oxo-2,2,12,12-tetramethyltridecanedioic acid diethyl ester (9.2 g, 25 mmol) was dissolved in methanol (200 mL) and the solution was cooled in an ice-water bath. Sodium borohydride (0.95 g, 25 mmol) was added. After 2 h, another portion of sodium borohydride (0.95 g, 25 mmol) was added and stirring was continued for 2 h. The reaction mixture was hydrolyzed with water (200 mL). The aqueous solution was extracted with dichloromethane (3×150 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to give the product (8.5 g, 92%) as an oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 4.11 (q, 4H, J=7.0 Hz), 3.60-3.50 (m, 1H), 1.66-1.32 (m, 11H), 1.24 (pseudo-t, 12H, J=7.0 Hz), 1.15 (s, 12H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm): 178.0, 71.7, 60.1, 42.1, 40.6, 37.3, 26.0, 25.1, 24.9, 14.2. HRMS (LSIMS, nba): Calcd. for C21H41O3 (MH+): 373.2954, found: 373.2936. HPLC: 88.90% purity.
Reaction SMILES: [C:1]([C:5]1[CH:11]=[C:10]([SH:12])[CH:9]=[C:8]([CH3:13])[C:6]=1[NH2:7])([CH3:4])([CH3:3])[CH3:2].[CH3:14][N:15]1[C:19](=[O:20])[CH:18]=[CH:17][C:16]1=[O:21].C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:14][N:15]1[C:19](=[O:20])[CH2:18][CH:17]([S:12][C:10]2[CH:9]=[C:8]([CH3:13])[C:6]([NH2:7])=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:11]=2)[C:16]1=[O:21]
Reactant: Cc1cc(S)cc(C(C)(C)C)c1N
Reactant: CN1C(=O)C=CC1=O
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: Cc1cc(SC2CC(=O)N(C)C2=O)cc(C(C)(C)C)c1N
Yield: 52.2 %

Procedure:
A stirred solution of 1.0 g (5 mmol) of 2-tert-butyl-4-mercapto-6-methylaniline, 0.6 g (5 mmol) of N-methylmaleimide and 0.1 g (1 mmol) of triethylamine in 10 mL of toluene is heated at 50° C. for 18 hours. The solvent is removed in vacuo and the residue is purified by flash chromatography (silica gel, 3:2, heptane:ethyl acetate eluent) followed by recrystallization from a heptane:toluene solvent mixture to give 0.8 g (51%) of the title compound as a white solid melting at 92°-94° C. 1HNMR (CDCl3) (90 MHz) 1.37 (s, 9H), 2.08 (s, 3H), 2.66 (dd, 1H), 3.06 (dd, 1H), 2.80 (s, 3H) 3.82 (dd, 1H) 4.02 (exchangeable s, 2H), 7.15 (meta d, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.Cl[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)=[CH:4][CH:3]=1
Reactant: Oc1ccc(S)cc1
Reactant: Clc1ccccn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Oc1ccc(Sc2ccccn2)cc1
Temperature: 75 °C
Yield: 91.8 %

Procedure:
Under nitrogen atmosphere, 127 g of 4-hydroxythiophenol, 112 g of chloropyridine, and 140 g of potassium carbonate were mixed. To the mixture was added 250 mL of dimethylformamide. The resultant was stirred, heated to 75° C. and further heated at 10° C. for 5 hours. At the time when the reaction completed substantially, the resultant was poured into 1.5 L of water. The precipitated crystals were collected by filtration, washed with water, and dried (yielded amount 184 g, and yield 91.8%).
Reaction SMILES: O=C1NC=[C:5]2[S:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[NH:9][C:4]2=[C:3]1[C:16]#[N:17].I[CH3:19].[CH3:20][N:21]([CH3:24])[CH:22]=[O:23]>O>[CH3:20][N:21]1[C:22](=[O:23])[C:3]([C:16]#[N:17])=[C:4]2[C:5]([S:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[N:9]2[CH3:19])=[CH:24]1
Reactant: CI
Reactant: N#Cc1c2c(c[nH]c1=O)Sc1ccccc1N2
Reactant: CN(C)C=O
Solvent: O
Product: CN1c2ccccc2Sc2cn(C)c(=O)c(C#N)c21

Procedure:
A mixture of 10 parts of 2,3-dihydro-3oxo-5H-pyrido[3,4-b][1,4]benzothiazine-4-carbonitrile, 45 parts of iodomethane, and 95 parts of N,N-dimethylformamide is heated at 100° for 2 hours, then diluted with 100 parts of water. The precipitate which forms is filtered out, dried in vacuo, and recrystallized from ethanol to give 2,3-dihydro-2,5-dimethyl-3-oxo-5H-pyrido[3,4-b][1,4]benzothiazine-4-carbonitrile melting at approximately 236°-237°.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:7][C@H:6]([O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[CH2:5][C:4](=[O:16])[CH2:3]1.ClC1C=CC=C(C(OO)=[O:25])C=1>>[OH:25][CH2:3][C@@H:4]1[O:16][C:2](=[O:1])[CH2:7][C@@H:6]([O:8][Si:9]([C:12]([CH3:13])([CH3:14])[CH3:15])([CH3:10])[CH3:11])[CH2:5]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1CC(=O)C[C@H](O)C1
Product: CC(C)(C)[Si](C)(C)O[C@@H]1CC(=O)O[C@@H](CO)C1
Reaction time: 20 h

Procedure:
reacting 3-hydroxy-5-(tert-butyldimethyl silyloxy)-(3R,5S)-cyclohexan-1-one having formula 7 with m-chloroperbezoic acid at room temperature for the period ranging from 16-24 hours, extracting with organic layer, washing with sodium metabisulphite, brine, drying and on evaporation to obtain 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4S,6R)-tetrahydro-2H-2-pyranone having formula 1,
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CI.[H-].[Na+].[CH3:29]COC(C)=O>C1COCC1.O>[CH2:1]([O:8][C:9]([N:11]([CH3:29])[C@H:12]([CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)CC[C@@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: CCOC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CI
Solvent: O
Product: CN(C(=O)OCc1ccccc1)[C@H](CCC(=O)OC(C)(C)C)C(=O)O
Temperature: 25 °C

Procedure:
To a solution of (R)-2-(((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid (1.41 g, 4.18 mmol) and MeI (2.091 mL, 33.4 mmol) in THF (12.66 ml) at 0° C. was slowly added NaH (0.501 g, 12.54 mmol) and the suspension was allowed to stir while warming up to room temperature for 24 hours. The reaction mixture was cooled to 0° C. before 10 mL of EtOAc were added along with 5 mL of water to quench the excess of NaH. The crude product was partitioned between a saturated NaHCO3 aqueous solution and Et2O. The two phases were separated and the organic phase was washed with a saturated NaHCO3 solution and both aqueous extracts were combined. The aqueous solution was brought to pH 3 using a 6N HCl aqueous solution. The aqueous phase was extracted with EtOAc, the organic extracts were combined and dried over anhydrous sodium sulfate. After filtration and concentration, (R)-2-(((benzyloxy)carbonyl)(methyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid was obtained as a yellow oil, 1.4 g (78%). LCMS showed the m/z of desired product, (M+Na)+ 374.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15](=[O:16])[N:14]3[CH:17]=[CH:18][S:19][C:13]3=[N:12][C:11]=2[CH3:20])=[CH:6][CH:5]=1)[CH3:2].[CH:21]1(CBr)C[CH2:22]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[CH:2]1([CH2:1][O:3][C:4]2[CH:5]=[CH:6][C:7]([C:10]3[C:15](=[O:16])[N:14]4[CH:17]=[CH:18][S:19][C:13]4=[N:12][C:11]=3[CH3:20])=[CH:8][CH:9]=2)[CH2:22][CH2:21]1
Reactant: CCOc1ccc(-c2c(C)nc3sccn3c2=O)cc1
Reactant: BrCC1CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1nc2sccn2c(=O)c1-c1ccc(OCC2CC2)cc1
Temperature: 80 °C

Procedure:
To a solution of Step 1 intermediate from Intermediate 10 (500 mg, 1.932 mmol) in DMF (5 ml) was added cyclopropylmethyl bromide (0.313 g, 2.321 mmol) at room temperature followed by Cs2CO3 (1.88 g, 5.770 mmol) and the reaction temperature was heated to 80° C. for 15.0 h overnight. The reaction mixture was diluted with ethyl acetate, washed with water and brine and purified by column chromatography using 1% methanol in chloroform to afford the desired compound; 1H NMR (300 MHz, CDCl3) δ 0.35-0.37 (m, 2H), 0.59-0.61 (m, 2H), 1.01-1.03 (m, 1H), 2.19 (s, 3H), 3.80-3.85 (m, 2H), 7.09-7.11 (m, 2H), 7.26-7.29 (m, 2H), 7.52 (d, J=4.8 Hz, 1H), 7.97 (d, J=4.5 Hz, 1H); MS (m/z) 313.25 (M+H)+.
Reaction SMILES: [Mg].Br[CH2:3][CH2:4][CH:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH2:18]([N:25]1[C:29]([CH:30]=[O:31])=[CH:28][N:27]=[CH:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.O>O1CCCC1>[CH2:18]([N:25]1[C:29]([CH:30]([OH:31])[CH2:3][CH2:4][CH:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[CH:28][N:27]=[CH:26]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: O=Cc1cncn1Cc1ccccc1
Reactant: BrCCC(c1ccccc1)c1ccccc1
Agent: [Mg]
Solvent: O
Solvent: C1CCOC1
Product: OC(CCC(c1ccccc1)c1ccccc1)c1cncn1Cc1ccccc1
Temperature: 25 °C

Procedure:
2,0 g of magnesium turnings are covered with 60 ml of dry tetrahydrofuran. To the mixture is then added dropwise a solution of 1-bromo-3,3-diphenylpropane (22,9 g) in 20 ml of dry tetrahydrofuran at such a rate that a smooth reaction is maintained. After the addition is complete, the reaction mixture is refluxed for one additional hour and cooled to room temperature. The reaction mixture is then added dropwise to a solution of 1-benzyl-5-imidazolecarbaldehyde (7,35 g) in 80 ml of tetrahydrofuran at 60° C. After the addition is complete, the reaction mixture is refluxed for 2 hours, cooled and poured into cold water. Tetrahydrofuran is evaporated and to the solution is added conc. hydrochloric acid. The solution is cooled and the precipitate which contains the product as hydrochloride salt is removed by filtration, washed with water and dried. Yield 14,1 g. M.p. 160°-168° C.
Reaction SMILES: CN(C)C=O.[CH3:6][CH:7]1[CH2:16][C:15]2[N:14]=[N:13][C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=3)=[CH:11][C:10]=2[CH:9]([OH:27])[CH2:8]1.Cl.CN(C)CCCN=C=NCC.[C:40]([O:44][C:45]([NH:47][C@@H:48]([C:56](O)=[O:57])[CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:46])([CH3:43])([CH3:42])[CH3:41]>C(O)C.C(OCC)(=O)C>[C:40]([O:44][C:45]([NH:47][C@@H:48]([C:56]([O:27][C@H:9]1[CH2:8][C@@H:7]([CH3:6])[CH2:16][C:15]2[N:14]=[N:13][C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=3)=[CH:11][C:10]1=2)=[O:57])[CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:46])([CH3:42])([CH3:43])[CH3:41]
Reactant: CC1Cc2nnc(-c3cccc(C(F)(F)F)c3)cc2C(O)C1
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCO
Solvent: CCOC(C)=O
Product: C[C@H]1Cc2nnc(-c3cccc(C(F)(F)F)c3)cc2[C@@H](OC(=O)[C@@H](Cc2ccccc2)NC(=O)OC(C)(C)C)C1
Yield: 29.5 %

Procedure:
To a N,N-dimethylformamide solution (181 mL) of 7-methyl-3-(3-trifluoromethylphenyl)-5,6,7,8-tetrahydrocinnolin-5-ol (27.8 g, 90.4 mmol) obtained in Example 6 were added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (26 g, 135.7 mmol) and N-(tert-butoxycarbonyl)-D-phenylalanine (31.2 g, 117.6 mmol) with washing in N-methylpyrrolidone (36 ml), followed by adding N,N-dimethylaminopyridine (1.2 mg, 9.0 mmol) to the mixed liquid under ice cooling, stirring over night, adding ethyl acetate (0.6 mL) and distilled water (0.3 L) and washing thus extracted organic layer with a 5% by weight aqueous solution of potassium hydrogen sulfate (400 mL), a saturated aqueous solution of sodium bicarbonate (300 mL) and a 10% saline solution (300 mL) sequentially. To residue obtained after concentration of the organic layer was added ethanol (187 mL) and stirred over night at room temperature. Crystal generated was filtered and washed with ethanol (35 mL) to obtain the titled objective compound (14.8 g).
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([O:8][C@@H:9]2[CH2:13][CH2:12][NH:11][C:10]2=[O:14])=[CH:4][CH:3]=1.[CH3:15][S-:16].[Na+].CN(C=O)C.O>CC(=O)OCC>[CH3:15][S:16][C:2]1[N:7]=[CH:6][C:5]([O:8][C@@H:9]2[CH2:13][CH2:12][NH:11][C:10]2=[O:14])=[CH:4][CH:3]=1
Reactant: C[S-]
Reactant: O=C1NCC[C@H]1Oc1ccc(Br)nc1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CSc1ccc(O[C@@H]2CCNC2=O)cn1
Temperature: 100 °C

Procedure:
A mixture of (R)-3-(6-bromo-pyridin-3-yloxy)-pyrrolidin-2-one (0.8 g), sodium methanethiolate (327 mg) and DMF (15 mL) was heated to 100° C. for 15 minutes. After the mixture reached room temperature, it was distributed between water and EA. The organic phase was dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC to provide the title compound. MS ESI+: m/z=225 [M+H]+.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH:10]=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N+:17]([CH3:20])([O-:19])=[O:18].[OH-].[Na+]>CO.O>[CH:1]1([O:6][C:7]2[CH:8]=[C:9](/[CH:10]=[CH:20]/[N+:17]([O-:19])=[O:18])[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1ccc(C=O)cc1OC1CCCC1
Reactant: C[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1ccc(/C=C/[N+](=O)[O-])cc1OC1CCCC1
Reaction time: 4 h

Procedure:
To a stirred solution of 1.02 g (4.63 mmol) of 3-cyclopentoxy-4-methoxybenzaldehyde in 20 mL of methanol was added 0.3 mL (5.5 mmol) of nitromethane followed by 0.2 g (5.0 mmol) of sodium hydroxide in 5 mL of water in single portions. The mixture was stirred for 4 hours after which time the decomposing mixture was concentrated, diluted with 20 mL of water and acidified to pH 1 with concentrated hydrochloric acid. The aqueous solution was extracted with three, 10 mL portions of chloroform and the combined organic fractions were dried over magnesium sulfate and concentrated. Liquid chromatography of the crude mixture over 100 g of silica gel eluting with 5% ethyl acetate in hexane provided an analytically pure solid.