Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([S:7]([N:10](S(C2SC(Cl)=CC=2)(=O)=O)[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])[CH:24]=3)[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[O:20][CH3:21])[N:13]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH2:30][CH2:31][N:32]([CH3:33])[CH3:34])[CH:24]=3)[N:12]=2)(=[O:8])=[O:9])=[CH:4][CH:3]=1
Reactant: COc1cccc2c1c(N(S(=O)(=O)c1ccc(Cl)s1)S(=O)(=O)c1ccc(Cl)s1)nn2Cc1cccc(OCCN(C)C)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1cccc2c1c(NS(=O)(=O)c1ccc(Cl)s1)nn2Cc1cccc(OCCN(C)C)c1
Temperature: 60 °C
Yield: 39 %

Procedure:
5-Chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[1-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)methyl]-4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 18) (140 mg, 0.2 mmol) was suspended in methanol (25 mL) and treated with 2M NaOH aqueous solution (2 mL). The mixture was heated to 60° C. for 4 h and then concentrated under reduced pressure. The residue was partitioned between 2M HCl (2 mL) and ethyl acetate. The aq. layer was back-extracted and the organic solution was washed with brine, dried (MgSO4) and evaporated. The residue was dissolved in 1:1 MeOH:DMSO (1.5 mL) and purified by MDAP on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier. Appropriate fractions were evaporated in vacuo to give the title product (40 mg, 39%). LCMS (System C) RT=2.29 min, ES+ve m/z 521/523 (M+H)+.
Reaction SMILES: [CH3:1][SH:2].C[O-].[Na+].Br[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]/[CH:12]=[C:13](\[NH:17][C:18]([CH:20]1[CH2:22][C:21]1([CH3:24])[CH3:23])=[O:19])/[C:14]([OH:16])=[O:15].N#N>CO>[CH3:23][C:21]1([CH3:24])[CH2:22][CH:20]1[C:18]([NH:17]/[C:13](=[CH:12]\[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][S:2][CH3:1])/[C:14]([OH:16])=[O:15])=[O:19]
Reactant: CS
Reactant: CC1(C)CC1C(=O)N/C(=C\CCCCCBr)C(=O)O
Agent: C[O-]
Agent: N#N
Agent: [Na+]
Solvent: CO
Product: CSCCCCC/C=C(\NC(=O)C1CC1(C)C)C(=O)O
Temperature: 25 °C

Procedure:
A stream of CH3SH gas was bubbled through a solution of 162 mg (3 mmoles) of sodium methoxide in 5 ml of methanol for 10 min. with cooling in an ice bath. The solution was allowed to warm to room temperature and 332 mg (1 mmole) of Z-8-bromo-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic acid was added. The solution was heated under reflux for 30 min. in a N2 atmosphere. Most of the methanol was evaporated under reduced pressure, the residue 2.5 N HCl. The precipitated oil was extracted with ether (3×). The ether extracts were washed with water, saturated brine and dried over MgSO4. Removal of the ether under reduced pressure gave a colorless oil that crystallized upon standing. It was recrystallized from ether-hexane to give 178 mg of Z-2-(2,2-dimethylcyclopropanecarboxamido)-8-methylthio-2-octenoic acid, m.p. 82°-84° C. Homogeneous by TLC (toluene-acetic acid, 4:1). The NMR spectrum was in accord with the desired structure
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2].C[CH2:16][N:17](C(C)C)C(C)C.Cl.CN>C(#N)C>[CH3:16][NH:17][C:7]1[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:11][N:10]=[C:9]([S:12][CH3:13])[N:8]=1
Reactant: CCN(C(C)C)C(C)C
Reactant: CCOC(=O)c1cnc(SC)nc1Cl
Agent: CN
Agent: Cl
Solvent: CC#N
Product: CCOC(=O)c1cnc(SC)nc1NC
Temperature: 100 °C
Reaction time: 3 h
Yield: 11.3 %

Procedure:
4-Chloro-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester (10 g, 429 mmol) was dissolved in acetonitrile to which DIPEA (4.34 g, 642 mmol) and methylamine hydrochloride (11.10 g, 858 mmol) was added. The reaction mixture was stirred at 100° C. for 3 hours, then cooled to room temperature and poured in to ice water. Off-white crystalline solid precipitated out. The solid was collected by filtration on a Buchner funnel and dried under vacuum to give the desired product (11 g). 1H NMR (DMSO-d6): δ 1.30 (t, J=7 Hz, 3H), δ 2.46 (s, 3H), δ 2.99 (d, J=5 Hz, 3H), δ 4.29 (q, J=7 Hz, 2H), δ 8.09 (br, s, 1H), δ 8.53 (s, 1H).
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:13][C@@H:12]([N:14]([CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=[CH:24][CH:23]=2)C(=O)C(F)(F)F)[CH2:11][CH2:10][N:9]1[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>>[CH2:1]([C@@H:8]1[CH2:13][C@@H:12]([NH:14][CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=[CH:24][CH:23]=2)[CH2:11][CH2:10][N:9]1[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)N1CC[C@H](N(Cc2ccnc3ccccc23)C(=O)C(F)(F)F)C[C@H]1Cc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Product: O=C(OCc1ccccc1)N1CC[C@H](NCc2ccnc3ccccc23)C[C@H]1Cc1ccccc1

Procedure:
80 mg (0.142 mmol) of (2R*,4S*)-2-benzyl-1-(benzyloxycarbonyl)-N-(4-quinolylmethyl)-N-trifluoroacetyl-4-piperidinamine are reacted with 22 mg (0.57 mmol) of sodium borohydride in analogy to Example 2. The title compound ##STR36## is obtained as colourless oil. TLC: methylene chloride/methanol/conc. ammonia (700:50:1) Rf =0.43, FD-MS: M+ =465.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1[S:10](=[O:20])(=[O:19])[N:11]([CH2:13][C:14]([O:16][CH2:17]C)=[O:15])[CH3:12])=O.C[O-].[Na+]>>[C:14]([C:13]1[N:11]([CH3:12])[S:10](=[O:20])(=[O:19])[C:9]2[CH:8]=[CH:7][S:6][C:5]=2[C:3]=1[OH:2])([O:16][CH3:17])=[O:15]
Reactant: CCOC(=O)CN(C)S(=O)(=O)c1ccsc1C(=O)OC
Agent: C[O-]
Agent: [Na+]
Product: COC(=O)C1=C(O)c2sccc2S(=O)(=O)N1C
Reaction time: 0.25 h

Procedure:
13.2 G. of 3-(N-carbethoxymethyl-N-methyl-sulfamoyl)-thiophene-2-carboxylic acid methyl ester are suspended in 42 ml. of a 1-N methanolic sodium methylate solution in the cold and under a nitrogen stream. After stirring for 15 minutes, a clear solution results. The solution is heated to reflux for 20 minutes, then cooled, neutralized and evaporated in vacuo. The residue is taken up in methylene chloride, shaken once each time with water and a sodium bicarbonate solution, dried and evaporated. The residue is brought to crystallization with methanol. There is obtained 3-carbomethoxy-4-hydroxy-2-methyl-2H-thieno[2,3-e]-1,2-thiazine 1,1-dioxide of melting point 193°-195° C.
Reaction SMILES: [CH3:1][C:2]1[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=O)[CH2:4][CH:3]=1.C1(C)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)(=O)C([Cl:29])=O>ClCCl.CN(C)C=O>[CH3:1][C:2]1[CH2:7][CH2:6][CH:5]([C:8]([Cl:29])=[O:10])[CH2:4][CH:3]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC1=CC[C@@H](C(=O)O)CC1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CC1=CCC(C(=O)Cl)CC1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
(1S)-4-Methyl-cyclohex-3-enecarboxylic acid (209 mg, 1.5 mmol), azeotropically dried by evaporation from toluene, was treated with potassium phosphate tribasic (383 mg, 1.8 mmol), suspended in dichloromethane (4 mL) and treated with dimethylformamide (2 drops). The reaction mixture was cooled to 0° C. and treated dropwise with oxalyl chloride (0.3 mL, 3.2 mmol). The reaction mixture was allowed to warm to ambient temperature while stirring for 2 h. After filtering the solids, the solution was concentrated, treated with hexanes and concentrated again to afford 4-methyl-cyclohex-3-enecarbonyl chloride (S) as a light yellow oil which was used immediately in the next step.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([C:25]2[C:30](Cl)=[N:29][CH:28]=[CH:27][N:26]=2)[NH:16][C:17](=O)[CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1C=C(C(NC(C2CCC2)=O)C2C(Cl)=NC=C[N:48]=2)C=CC=1)C1C=CC=CC=1>>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH2:18][CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[N:26]3[CH:27]=[CH:28][N:29]=[C:30]([NH2:48])[C:25]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(NC(c1cccc(OCc2ccccc2)c1)c1nccnc1Cl)C1CCC1
Reactant: O=C(CC1CCCC1)NC(c1cccc(OCc2ccccc2)c1)c1nccnc1Cl
Product: Nc1nccn2c(CC3CCCC3)nc(-c3cccc(OCc4ccccc4)c3)c12

Procedure:
N-[(3-Benzyloxyphenyl)-(3-chloropyrazin-2-yl)-methyl]-2-cyclopentyl-acetamide: Prepared according to the procedures for Cyclobutanecarboxylic Acid [(3-benzyloxy-phenyl)-(3-chloro-pyrazin-2-yl)-methyl]Amide, White solid, MS (ES) 436.32 (M+1).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[CH2:5][CH2:6][CH2:7][C:8](=[O:24])[C:9]=2[CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=2)[C:11]=1C(O)=O.S(=O)(=O)(O)O>C(O)C>[CH3:1][C:2]1[NH:3][C:4]2[CH2:5][CH2:6][CH2:7][C:8](=[O:24])[C:9]=2[CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=2)[CH:11]=1
Reactant: CC1=C(C(=O)O)C(c2cccc([N+](=O)[O-])c2)C2=C(CCCC2=O)N1
Agent: O=S(=O)(O)O
Solvent: CCO
Product: CC1=CC(c2cccc([N+](=O)[O-])c2)C2=C(CCCC2=O)N1
Yield: 39.6 %

Procedure:
2-Methyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydro-3-quinolinecarboxylic acid (4.66 g) was suspended in ethanol (200 mL) with concentrated sulfuric acid (0.5 mL). The mixture was heated at reflux for 5 h, during which time all of the solid went into solution. The solvent was evaporated, and the residue was partitioned between aqueous 2N sodium hydroxide and ethyl acetate. The aqueous portion was extracted with ethyl acetate. The combined extracts were washed (water, brine), dried, and evaporated to yield a residue which was purified by chromatography, eluting with ethyl acetate, to afford the title compound as a pale yellow solid (1.6 g); mp 183°-185° C.; MS: 284 (M); 250 MHz NMR: 1.76 (s,3, CH3), 187 (m,2, CH2), 2.16 (m,2, CH2), 2.46 (m,2, CH2), 4.58 (d,1, J=4.9, CH), 4.64 (d,1, J=4.9, CH), 7.53 (t, 1, 7.6, Ar), 7.62 (d, 1, J=7.6, Ar), 7.96 (s,1, Ar), 7.98 (m,1, Ar), 8.80 (s,1, NH). Analysis for C16H16N2O3 :Calculated: C, 67.59; H, 5.67; N, 9.85; Found: C, 67,44; H, 5.75; 9.56.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][C:6]=1[OH:14])([CH3:4])([CH3:3])[CH3:2].Br[CH2:16][CH2:17][O:18][CH2:19][CH3:20]>CC#N>[CH2:17]([O:18][CH2:19][CH2:20][O:14][C:6]1[CH:7]=[C:8]([NH2:11])[CH:9]=[CH:10][C:5]=1[C:1]([CH3:4])([CH3:3])[CH3:2])[CH3:16]
Reactant: CC(C)(C)c1ccc([N+](=O)[O-])cc1O
Reactant: CCOCCBr
Solvent: CC#N
Product: CCOCCOc1cc(N)ccc1C(C)(C)C

Procedure:
3-(2-Ethoxyethoxy)-4-tert-butylbenzenamine (C-3) was synthesized following the general scheme above starting from 2-tert-butyl-5-nitrophenol (C-1-a) and 1-bromo-2-ethoxyethane. 1H NMR (400 MHz, CDCl3) δ 6.97 (d,J=7.9 Hz, 1H), 6.17 (s, 1H), 6.14 (d,J=2.3 Hz, 1H), 4.00 (t,J=5.2 Hz, 2H), 3.76 (t,J=5.2 Hz, 2H), 3.53 (q,J=7.0 Hz, 2H), 1.27 (s, 9H), 1.16 (t,J=7.0 Hz, 3H); HPLC ret. time 2.55 min, 10-99% CH3CN, 5 min run; ESI-MS 238.3 m/z (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:14]2=[C:15]3[N:10]([CH2:11][CH2:12][CH2:13]2)[CH2:9][CH2:8][CH2:7][C:6]3=[CH:5][C:4]=1[CH:16]=[CH:17][C:18]1[S:19][CH:20]=[CH:21][CH:22]=1.C([Li])CCC.CN(C)[CH:30]=[O:31].O>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[C:14]2=[C:15]3[N:10]([CH2:11][CH2:12][CH2:13]2)[CH2:9][CH2:8][CH2:7][C:6]3=[CH:5][C:4]=1[CH:16]=[CH:17][C:18]1[S:19][C:20]([CH:30]=[O:31])=[CH:21][CH:22]=1
Reactant: CN(C)C=O
Reactant: COc1c(C=Cc2cccs2)cc2c3c1CCCN3CCC2
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: COc1c(C=Cc2ccc(C=O)s2)cc2c3c1CCCN3CCC2
Temperature: -70 °C
Reaction time: 1 h
Yield: 35.5 %

Procedure:
In a stream of argon, in 25 ml of tetrahydrofuran was dissolved 1.29 g (4.14 mmol) of 8-methoxy-9-[2-(thiophene-2-yl)vinyl]-2,3,6,7-tetrahydro-1H,5H-benzo[ij]quinolizine, and 3.9 ml of n-butyllithium (1.6 mol solution in hexane) (6.24 mmol) was added dropwise thereto under cooling at −70° C. After the mixture was stirred for 1 hour, 0.43 g (5.88 mmol) of N,N-dimethylformamide was added dropwise thereto. The reaction mixture was stirred for 1 hour and the temperature was allowed to rise. To this mixture, 10 ml of water was added dropwise. After the reaction mixture was added to water, extraction with ethyl acetate, washing with a saturated saline solution, drying over anhydrous sodium sulfate, and concentration were performed. The residual liquid was dissolved in 300 ml of ether and 50 mg of iodine pieces were added thereto. After stirred at room temperature, the mixture was washed with a 5% sodium bisulfite solution and then with a saturated saline solution. Drying over anhydrous sodium sulfate and concentration were performed. The residue was purified by silica gel column chromatography to give 496 mg of a dark reddish brown oily matter (yield: 35.5%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][N:7]([CH2:9][C@H:10]([OH:13])[CH2:11][OH:12])[CH:8]=1)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:5]=[N:6][N:7]([CH2:9][C@H:10]([OH:13])[CH2:11][OH:12])[CH:8]=1
Reactant: O=[N+]([O-])c1cnn(C[C@H](O)CO)c1
Agent: [Pd]
Solvent: CO
Product: Nc1cnn(C[C@H](O)CO)c1

Procedure:
(S)-3-(4-Nitro-pyrazol-1-yl)-propane-1,2-diol (29) (180 mg, 10 mmol), and 10% Pd/C (116 mg) in methanol (20 mL) were stirred under hydrogen for at atmospheric pressure and room temperature for 48 h. The reaction mixture was subsequently filtered through celite and concentrated to give A3-2 (160 mg, 100%); LCMS, Rt=0.28 min (MeOH-FA method), m/z 158 (MH+).
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([Cl:17])=[C:5]([CH:10]=[CH:11][C:12]=1[S:13]([CH3:16])(=[O:15])=[O:14])[C:6]([O:8][CH3:9])=[O:7].C1OCCOCCOCCOCCOCCOC1.[C-:36]#[N:37].[K+]>C(#N)C>[Cl:17][C:4]1[C:3]([CH2:2][C:36]#[N:37])=[C:12]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7]
Reactant: [C-]#N
Reactant: COC(=O)c1ccc(S(C)(=O)=O)c(CBr)c1Cl
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccc(S(C)(=O)=O)c(CC#N)c1Cl
Reaction time: 72 h
Yield: 97.4 %

Procedure:
5.0 g of methyl 3-bromomethyl-2-chloro-4-methanesulfonylbenzoate was added to a solution of 0.4 g of 18-crown-6 and 1.9 g of potassium cyanide in 50 ml of acetonitrile. The mixture was stireed for 72 hours at room temperature. After filtering off the solid, water was added to the filtrate, and the mixture was extracted with chloroform. After washing the extract with water and drying it, the solvent was distilled off to obtain a crude product. The crude product was purified by short silica gel column chlomatography (eluent: chloroform) to obtain 4.1 g of the desired product. Melting point: 151°-155° C.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:30][CH:31]([CH2:34][CH2:35][CH3:36])[CH:32]=O.[H-].[Na+]>C(#N)C.O>[CH3:30][CH:31]([CH2:34][CH2:35][CH3:36])[CH:32]=[CH:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: CCOC(=O)CCCCBr
Reactant: CCCC(C)C=O
Agent: [H-]
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: O
Product: CCCC(C)C=CCCCC(=O)OCC
Yield: 54 %

Procedure:
104.54 g (0.5 mol) of ethyl 5-bromovalerate and 137.5 g (0.525 mol) of triphenyl phosphine were refluxed for 36 hours in 1 l of acetonitrile. After the reaction terminated, 500 ml of acetonitrile was distilled off, then the reaction mixture was dried. Under nitrogen atmosphere, 50.1 g (0.5 mol) of 2-methyl valeraldehyde was added, then the reaction mixture was stirred. Controlling the reaction temperature to within the range of 25°-35° C., 20.0 g (0.5 mol) of oily (60%) sodium hydride was added little by little. After the addition, the reaction mixture was stirred over night at room temperature. After the reaction ended, 250 g of water was added into the reaction mixture, then oil layer was separated and the water layer was extracted three times with 150 ml of hexane. The organic layers were combined and washed with 150 ml of water. After the hexane solution was dried sufficiently with anhydrous Magnesium sulfate, solvent was removed under reduced pressure, and distilled to obtain 57.3 g of ethyl 7-methyl-5-decenoate (Yield: 54%, based upon starting material). The product was gradually added dropwise into 500 ml of dried ethylether solution including 5.12 g (0.135 mol) of aluminum lithium hydride under nitrogen stream. The dropwise addition was done while a reaction vessel was cooled sufficiently by ice water. After the addition was completed, the reaction temperature was returned to room temperature and stirred for 2 hours. Then, 300 ml of water was added gradually into the reaction mixture, and the organic layer was separated. The water layer was returned to pH7 and extracted three times with 100 ml of diethylether. The organic layers were combined and washed with 100 ml of water, and solvent was removed from the reaction mixture under reduced pressure to obtain 44.2g of 7-methyl-5-decen-1-ol (Yield: 52", based upon starting material).
Reaction SMILES: [Cl:1][Si](C)(C)C.[CH3:6][N:7]([CH:9]1[CH2:14][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][CH2:11][C:10]1=[CH:21][C:22]([NH:24][CH2:25][CH2:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)=[O:23])[CH3:8]>CC(CC)=O>[ClH:1].[CH3:6][N:7]([CH:9]1[CH2:14][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:12][CH2:11][C:10]1=[CH:21][C:22]([NH:24][CH2:25][CH2:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)=[O:23])[CH3:8]
Reactant: C[Si](C)(C)Cl
Agent: CN(C)C1CC(c2ccccc2)CCC1=CC(=O)NCCc1c[nH]c2ccccc12
Solvent: CCC(C)=O
Product: Cl
Reaction time: 2 h

Procedure:
Chlorotrimethylsilane (0.034 ml, 0.26 mmol) was added to the solution of 2-(dimethylamino-4-phenylcyclohexylidene)-N-[2-(1H-indol-3-yl)ethyl]acetamide (75 mg, 0.178 mmol) in ethyl methyl ketone (15 ml). After 2 h it was possible to isolate the hydrochloride as a beige-coloured solid in a yield of 75% (61 mg) with an m.p. of 203-207° C.
Reaction SMILES: [BH4-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][C:13]1[O:12][C:11](=[O:19])[C:10]([N:20]3[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[N:21]3)=[CH:9][C:8]2=1.Cl.CO>O1CCCC1>[OH:19][CH2:11][CH:10]([N:20]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[N:21]1)[CH2:9][C:8]1[C:7]2[C:16](=[CH:17][CH:18]=[C:5]([O:4][CH3:3])[CH:6]=2)[N:15]=[CH:14][C:13]=1[OH:12]
Reactant: COc1ccc2ncc3oc(=O)c(-n4cc([N+](=O)[O-])cn4)cc3c2c1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc2ncc(O)c(CC(CO)n3cc([N+](=O)[O-])cn3)c2c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 83.7 %

Procedure:
Sodium borohydride (179 mg, 4.73 mmol, 8.0 eq) is added at 0° C. to a stirred solution of 6-methoxy-3-(4-nitro-pyrazol-1-yl)-1-oxa-9-aza-phenanthren-2-one (200 mg, 0.59 mmol, 1.0 eq) in tetrahydrofuran (50 mL). After 2 hours stirring at 0° C., the reaction mixture is cautiously acidified to pH=1 with a 4N hydrochloric acid aqueous solution. Tetrahydrofuran is evaporated and the residue is extracted with ethyl acetate (3×40 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ethyl acetate:methanol, 20:1, v/v) to afford 4-[3-hydroxy-2-(4-nitro-pyrazol-1-yl)-propyl]-6-methoxy-quinolin-3-ol as a white solid (170 mg, 84% yield).
Reaction SMILES: [Cl:1][C:2]1[S:11][C:10]2[C:9](=O)[C:8](=[CH:13][N:14](C)[CH3:15])[CH2:7][CH2:6][N:5]([C:17](=O)[C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)[C:4]=2[CH:3]=1.C[NH:29]N>CO>[Cl:1][C:2]1[S:11][C:10]2[C:9]3=[N:29][N:14]([CH3:15])[CH:13]=[C:8]3[CH2:7][CH2:6][N:5]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)[C:4]=2[CH:3]=1
Reactant: CN(C)C=C1CCN(C(=O)c2ccc([N+](=O)[O-])cc2)c2cc(Cl)sc2C1=O
Reactant: CNN
Solvent: CO
Product: Cn1cc2c(n1)-c1sc(Cl)cc1N(Cc1ccc([N+](=O)[O-])cc1)CC2
Temperature: 80 °C

Procedure:
A mixture of 500 mg of 2-chloro-7-[(dimethylamino)methylene]-4,5,6,7-tetrahydro-4-(4-nitrobenzoyl)-8H-thieno[3,2-b]azepin-8-one in 15 ml of absolute methanol is stirred under argon while 131 μl of N-methylhydrazine is added. The reaction mixture is heated at 80° C. for 18 hours. The reaction mixture is cooled to room temperature and concentrated in vacuo to give 420 mg of the desired product as a solid.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][O:6][CH2:5][C@@H:4]([CH3:8])[NH:3]1.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.[NH2:42][C:43]1[CH:51]=[CH:50][C:46]([C:47](O)=[O:48])=[CH:45][N:44]=1>CN(C=O)C>[NH2:42][C:43]1[N:44]=[CH:45][C:46]([C:47]([N:3]2[C@@H:4]([CH3:8])[CH2:5][O:6][CH2:7][C@H:2]2[CH3:1])=[O:48])=[CH:50][CH:51]=1
Reactant: C[C@@H]1COC[C@H](C)N1
Reactant: Nc1ccc(C(=O)O)cn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@@H]1COC[C@H](C)N1C(=O)c1ccc(N)nc1
Reaction time: 18 h
Yield: 27.6 %

Procedure:
To a solution of (3S,5R)-3,5-dimethylmorpholine (1.15 g, 10 mmol) in DMF (15 mL) was added HATU (3.8 g, 10 mmol), DIPEA (2.6 g, 20 mmol), and 6-aminonicotinic acid (1.38 g, 10 mmol) at room temperature. The reaction mixture was stirred for 18 h. It was then filtered and the filtrate was purified with Combiflash (A: 1% NH4HCO3/water, B: acetonitrile) to afford 320a (650 mg, 27%) as a yellow solid. MS-ESI: [M+H]+ 236.1.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][NH2:18])[CH:12]=1>C1C=CC=CC=1>[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][NH:18][C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([SH:1])=[CH:3][CH:4]=2)=[O:10])[CH:12]=1
Reactant: O=C=Nc1ccc(S)cc1
Reactant: NCc1cccnc1
Solvent: c1ccccc1
Product: O=C(NCc1cccnc1)Nc1ccc(S)cc1
Temperature: 25 °C
Yield: 77.5 %

Procedure:
To 4-mercaptophenyl isocyanate (0.9 g., 0.006 mol) in 50 ml. of anhydrous benzene was added 3-pyridylmethylamine (0.65 g., 0.006 mol). An exothermic reaction caused the temperature to rise to 40°C. and a white precipitate formed. The reaction mixture was momentarily heated to reflux, then cooled to room temperature and filtered to give 1.2 g. melting at 155°-159°C. The product was a 77.5% yield of 1-(3-pyridylmethyl)-3-(4-mercaptophenyl)urea.
Reaction SMILES: [CH3:1][CH:2]1[C:14](=[O:15])[C:5]2=[C:6]3[C:11](=[CH:12][CH:13]=[C:4]2[CH2:3]1)[CH:10]=[CH:9][CH:8]=[CH:7]3.[H-].[H-].[H-].[H-].[Li+].[Al+3].Cl>C1COCC1.CCOCC>[CH3:1][CH:2]1[CH:14]([OH:15])[C:5]2=[C:6]3[C:11](=[CH:12][CH:13]=[C:4]2[CH2:3]1)[CH:10]=[CH:9][CH:8]=[CH:7]3
Reactant: CC1Cc2ccc3ccccc3c2C1=O
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC1Cc2ccc3ccccc3c2C1O

Procedure:
A solution of 2-methyl-2,3-dihydro-1H-cyclopenta[a]naphtalen-1-one (28.09 g, 0.143 mol) in 100 mL of THF was slowly added to a suspension of LiAlH4 (2.18 g, 58 mmol) in 200 mL of ether and refluxed for 2 h under stirring. The reaction mixture was subsequently transferred into a 2-L beaker and slowly hydrolyzed, under constant stirring, by dropwise addition of a 10% aq. solution of HCl until pH 5. The organic layer was separated, while the water layer was extracted with ether (3×100 mL). The organic layers were collected, washed with potassium carbonate/water until neutral pH, dried over MgSO4 and evaporated off to dryness. The so-obtained product, as a mixture of two isomers, was used in the next step without further purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH2:11][NH2:12].[CH3:13][S:14](Cl)(=[O:16])=[O:15]>N1C=CC=CC=1.ClCCl>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH2:11][NH:12][S:14]([CH3:13])(=[O:16])=[O:15]
Reactant: NCc1ccc([N+](=O)[O-])cc1F
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CS(=O)(=O)NCc1ccc([N+](=O)[O-])cc1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.3 %

Procedure:
To a stirred solution of (2-fluoro-4-nitrophenyl)methanamine (194 mg, 1.140 mmol) in pyridine, cooled to 0° C., were added methanesulfonyl chloride (248 mg, 2.166 mmol). The resulting reaction mixture was stirred for 1 h at room temperature. The mixture was dissolved in dichloromethane and washed with 1N HCl. The organic layer was dried over magnesium sulfate and filtered. The filtrate removed in vacuo. The crude was purified by column chromatography. N-(2-Fluoro-4-nitrobenzyl)methanesulfonamide (250 mg) was obtained as 88% yield.