Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].I[CH2:18][CH3:19].[BH4-].[Na+]>C(O)C>[CH2:18]([N:14]1[CH2:15][CH:16]=[C:11]([C:10]2[C:2]([F:1])=[C:3]([CH:7]=[CH:8][CH:9]=2)[C:4]([NH2:6])=[O:5])[CH2:12][CH2:13]1)[CH3:19]
Reactant: CCI
Reactant: NC(=O)c1cccc(-c2ccncc2)c1F
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CCN1CC=C(c2cccc(C(N)=O)c2F)CC1

Procedure:
Preparation according to preparation 6: 2-fluoro-3-pyridin-4-ylbenzamide (0.94 g, 4.34 mmol), 1-iodoethane (3 ml), ethanol (40 ml), sodium borohydride (1.25 g, 34.8 mmol). Yield: 0.75 g. MS m/z (rel. intensity, 70 eV) 248 (M+, bp), 247 (37), 233 (99), 146 (22), 110 (41).
Reaction SMILES: C[O-].[Na+].CO.[CH3:6][O:7][CH:8]([C:13]([O:15]C)=O)[C:9](OC)=[O:10].C(O)(=O)C.[CH:21]([NH2:23])=[NH:22]>>[CH3:6][O:7][C:8]1[C:13]([OH:15])=[N:22][CH:21]=[N:23][C:9]=1[OH:10]
Reactant: N=CN
Reactant: COC(=O)C(OC)C(=O)OC
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: COc1c(O)ncnc1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.8 %

Procedure:
A 2-liter, three-necked, round-bottomed flask equipped with a mechanical stirrer and a reflux condenser was dried at 100° C. and cooled to 25° C. under N2. Methanol (260 mL) was added, followed by a solution of sodium methoxide in methanol (25% by weight, 670 mL, 3.10 mol). The resulting solution was cooled to 0° C. Dimethyl methoxymalonate (151 g, 0.930 mol) was added in one portion, followed by formamidine acetate (100 g, 0.96 mol). The temperature was kept below 10° C. The resulting suspension was then stirred at 0° C. for 30 min, and refluxed for 1 h. The resulting suspension was cooled to 0° C. and quenched with concentrated HCl (250 mL) over 30 min, during which time the temperature was kept below 10° C. Stirring was continued at 5° C. for 30 min. The suspension was then filtered. The filter cake was re-suspended in water (1000 mL) and refluxed until a nearly clear solution was obtained. The solution was filtered while hot. The filtrate was cooled to 0-5° C. and stirred for 1 h. The solid precipitate was collected by filtration, washed with cold methanol (500 mL), and dried in a vacuum oven at 50° C. for 1 h to give the title compound (96.2 g, 73% yield) as a white solid. Exact Mass calculated for C5H6N2O3: 142.0, LCMS m/z=143.2 (M+H+); 1H NMR (400 MHz, DMSO-d6) δ 3.63 (s, 3H), 7.81 (s, 1H), 11.75 (br s, 2H).
Reaction SMILES: C(OC([NH:8][C:9]1[C:10]([C:16]([OH:18])=[O:17])=[CH:11][C:12]([Cl:15])=[N:13][CH:14]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:8][C:9]1[C:10]([C:16]([OH:18])=[O:17])=[CH:11][C:12]([Cl:15])=[N:13][CH:14]=1
Reactant: CC(C)(C)OC(=O)Nc1cnc(Cl)cc1C(=O)O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Nc1cnc(Cl)cc1C(=O)O
Reaction time: 8 h
Yield: 86.9 %

Procedure:
A stirred suspension of 5-[N-(tert-butoxycarbonyl)amino]-2-chloropyridine-4-carboxylic acid (1.91 g, 7 mmol) in CH2Cl2 (200 mL) is treated slowly with trifluoroacetic acid until homogeneous (ca. 12 mL). The solution is stirred overnight and extracted with dilute NH4OH, and the aqueous layer is then acidified with dilute HCl to gave a precipitate of 5-amino-2-chloropyridine-4-carboxylic acid (1.05 g, 87% yield). 1H NMR (DMSO) δ 9.01 (2H, m), 8.03 (1H, s), 7.48 (1H, s).
Reaction SMILES: [Cl:1][S:2]([C:5]1[S:6][C:7]([Cl:10])=[CH:8][CH:9]=1)(=[O:4])=[O:3].[N+:11]([O-])([OH:13])=[O:12]>>[Cl:1][S:2]([C:5]1[S:6][C:7]([Cl:10])=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=1)(=[O:4])=[O:3]
Reactant: O=[N+]([O-])O
Reactant: O=S(=O)(Cl)c1ccc(Cl)s1
Product: O=[N+]([O-])c1cc(S(=O)(=O)Cl)sc1Cl
Temperature: 50 °C
Reaction time: 2 h

Procedure:
2--Chlorosulphonyl-5-chlorothiophene (19.8 parts) was added to fuming nitric acid (80 parts), allowing to exotherm to 35° C. Heated to 50° C. and stirred under these conditions for 2 hours. Cooled to room temperature then poured onto ice/water with vigorous stirring. The white solid was filtered off and dried to yield the product 2-chlorosulphonyl-4-nitro-5-chlorothiophene (19 parts).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.Br[CH2:16][CH2:17][CH2:18][O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[CH2:20]([O:19][CH2:18][CH2:17][CH2:16][N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: BrCCCOCc1ccccc1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)OB(c2cnn(CCCOCc3ccccc3)c2)OC1(C)C
Temperature: 90 °C
Reaction time: 8 h

Procedure:
A solution of 4-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (8.47 g, 43.6 mmol) in DMF (85 mL) was treated with 1-bromo-3-benzyloxypropane (10.0 g, 43.6 mmol) and Cs2CO3 (14.2 g, 43.6 mmol). This mixture was heated to 90° C. and allowed to stir under N2 overnight. The reaction mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with water 3 times, once with brine, dried over Na2SO4, filtered and concentrated to an orange oil which was purified on a Teledyne ISCO Combiflash® Rf system (0-30% EtOAc/DCM) to afford the title compound as 8.5 g of a clear oil (57%). 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.66 (s, 1H), 7.29-7.40 (m, 5H), 4.48 (s, 2H), 4.26 (t, J=6.8 Hz, 2H), 3.43 (t, J=5.9 Hz, 2H), 2.16 (quin, J=6.3 Hz, 2H), 1.60 (dd, J=6.6, 8.6 Hz, 2H), 1.33 (s, 12H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[NH:7][CH2:8][CH2:9][CH2:10][NH:11][CH:12]([C:16]1[N:17]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:18](=[O:26])[C:19]2[C:24]([CH3:25])=[N:23][S:22][C:20]=2[N:21]=1)[CH:13]([CH3:15])[CH3:14])([CH3:4])([CH3:3])[CH3:2].[C:35]1([CH3:44])[CH:40]=[CH:39][C:38]([C:41](Cl)=[O:42])=[CH:37][CH:36]=1>N1C=CC=CC=1.C(Cl)Cl>[C:1]([O:5][C:6](=[O:34])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH:12]([C:16]1[N:17]([CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:18](=[O:26])[C:19]2[C:24]([CH3:25])=[N:23][S:22][C:20]=2[N:21]=1)[CH:13]([CH3:15])[CH3:14])[C:41](=[O:42])[C:38]1[CH:39]=[CH:40][C:35]([CH3:44])=[CH:36][CH:37]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: Cc1ccc(C(=O)Cl)cc1
Reactant: Cc1nsc2nc(C(NCCCNC(=O)OC(C)(C)C)C(C)C)n(Cc3ccccc3)c(=O)c12
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccc(C(=O)N(CCCNC(=O)OC(C)(C)C)C(c2nc3snc(C)c3c(=O)n2Cc2ccccc2)C(C)C)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a solution of the crude {3-[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-2-methyl-propylamino]-propyl}-carbamic acid tert-butyl ester (method 31) in pyridine (10 mL) at r.t., a solution of the p-toluoyl chloride (0.616 g, 4 mmol) in DCM (10 mL) was added dropwise and the resulting solution was stirred at r.t. for 2 days. The reaction mixture was diluted with DCM (100 mL) washed with water (2×100 mL), brine (100 mL) and dried (Na2SO4). Concentration of the organic layer provided the crude product which was purified by column (silica gel) chromatography using 20-30% EtOAc in hexanes as eluent. Product isolated was 0.276 g. m/z 604 (MH+).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.O.Cl.[NH:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1>>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:16]3[CH2:17][CH2:18][NH:13][CH2:14][CH:15]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C1CCNCC1
Reactant: Cc1ccc2cc[nH]c2c1
Agent: Cl
Solvent: O
Product: Cc1ccc2c(C3=CCNCC3)c[nH]c2c1
Yield: 18.5 %

Procedure:
Beginning with 3.0 gm (28.0 mMol) 6-methyl-1H-indole and 7.04 gm (45.7 mMol) 4-piperidone hydrochloride monohydrate, 1.1 gm (22%) of the title compound were recovered as a tan powder.
Reaction SMILES: [OH-].[K+].Cl.O.[NH:5]1[CH2:10][CH2:9][C:8](=O)[CH2:7][CH2:6]1.[CH3:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][NH:19]2)=[CH:15][CH:14]=1>CO>[CH3:12][C:13]1[CH:21]=[C:20]2[C:16]([C:17]([C:8]3[CH2:7][CH2:6][NH:5][CH2:10][CH:9]=3)=[CH:18][NH:19]2)=[CH:15][CH:14]=1
Reactant: Cc1ccc2cc[nH]c2c1
Reactant: O=C1CCNCC1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1ccc2c(C3=CCNCC3)c[nH]c2c1
Yield: 92.7 %

Procedure:
To a solution of potassium hydroxide (16 g) in methanol were added at 5° C. 4-piperidone hydrate hydrochloride (30 g) and a solution of 6-methyl-1H-indole (10 g) in methanol (50 ml). The mixture was refluxed for 16 hours. After cooling precipitated inorganic salts were filtered off. Methanol was evaporated and the remaining oil was dissolved in ethyl acetate (200 ml) and subsequently washed with brine (2×100 ml). After drying (anh. MgSO4) the solvent was evaporated leaving 15 g of crude 6-methyl-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole, which was used without further purification. The pure tetrahydropyridyl derivative crystallized from diethyl ether. Mp: 150°-152° C. To a solution of 1-(2-chloroethyl)-3-(2-propyl)-2-imidazolidinon (32 g) in MIBK (500 ml) were added 6-methyl-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (15 g), potassium carbonate (16 g) and potassium iodide (5 g). The mixture was refluxed for 19 hours and finally filtered while still hot. MIBK was evaporated and the resulting oil was dissolved in ethyl acetate (500 ml) and washed with brine (2×100 ml). After drying (anh. Na2SO4) ethyl acetate was evaporated. The remaining oil was stirred with diethyl ether (200 ml) and the precipitated, crystalline 3-[1-[2-[3-(2-propyl)-2-imidazolidinon-1-yl]ethyl]-1,2,3,6-tetrahydro-4-pyridyl]-6-methyl-1H-indole was filtered off. Yield: 14.5 g. Mp: 170°-174° C. To a solution of the thus prepared imidazolidinon derivative (14 g) in acetic acid (300 ml), was added PtO2 (600 mg). This mixture was hydrogenated in a Parr apparatus at 3 atm. for 72 hours. The catalyst was filtered off and most of the acetic acid was evaporated in vacuo. The remaining oil was dissolved in H2O and pH was adjusted to 9-10 by addition of dil. NaOH solution. The title compound 14a was extracted with dichloromethane (2×200 ml) and isolated as above. The crude product was purified by eluting (eluent:ethyl acetate/dichloromethane/ethanol/triethylamine (40:40:20:5) through silica gel. Yield: 4.5 g. Mp: 185° C.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([CH2:7][NH:8][C:9]2[CH:18]=[CH:17][C:16]3[C:15]([CH:19]=[O:20])=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=2)=[CH:4][CH:3]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH3:1][C:2]1[O:6][C:5]([CH2:7][NH:8][C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[CH2:19][OH:20])[N:10]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(CNc2ccc3c(C=O)cccc3n2)o1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Product: Cc1ccc(CNc2ccc3c(CO)cccc3n2)o1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-[(5-Methyl-furan-2-ylmethyl)-amino]-quinoline-5-carbaldehyde (150 mg, 0.56 mmol) was dissolved in 5 mL dichloroethan. Acetic acid (136 mg, 2.3 mmol) and sodium triacetoxy borohydride (258 mg, 1.2 mmol) were added. The reaction mixture was stirred at room temperature overnight and quenched by addition of 2N sodium carbonate solution (50 mL). The mixture was extracted three times with ethyl acetate (100 mL each). The organic phases were pooled, dried with sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography on silica gel (heptane/ethyl acetate 100:0->50:50 gradient). The title compound was obtained as a light brown solid (105 mg, 69%), MS: m/e=269.5 (M+H+).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[CH:5]([NH:11][C:12](=[O:14])[CH3:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[O-]CC.[Na+].[Na].Br[CH:22]([C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1)[CH3:23]>C(O)C>[CH2:9]([O:8][C:6](=[O:7])[C:5]([NH:11][C:12](=[O:14])[CH3:13])([CH:22]([C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1)[CH3:23])[C:4]([O:3][CH2:1][CH3:2])=[O:15])[CH3:10]
Reactant: CC(Br)c1cccc2ccccc12
Reactant: CCOC(=O)C(NC(C)=O)C(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C(NC(C)=O)(C(=O)OCC)C(C)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2-Acetylaminopropanedioic acid diethyl ester (20.8 g) was added to a solution of sodium ethoxide in ethanol (prepared from sodium (2.2 g) and ethanol (100 ml). After the mixture was stirred for 10 minutes at ambient temperature, 1-(1-bromoethyl)naphthalene was added. The reaction mixture was stirred for 18 hours at room temperature. The precipitated solid was collected by filtration and dissolved in chloroform. The chloroform solution was dried over magnesium sulfate and evaporated to give 2-acetylamino-2-[1-(1-naphthyl)ethyl]propanedioic acid diethyl ester (21.59 g).
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[C:23]([NH2:25])[CH:22]=[CH:21][C:3]=1[C:4]([N:6]1[CH2:12][C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[CH2:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2)=[O:5].C(N(CC)C(C)C)(C)C.[CH3:35][C:36]1[CH:44]=[CH:43][CH:42]=[CH:41][C:37]=1[C:38](Cl)=[O:39]>>[CH:17]1[C:8]2[CH2:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[CH2:12][N:6]([C:4]([C:3]3[CH:21]=[CH:22][C:23]([NH:25][C:38](=[O:39])[C:37]4[CH:41]=[CH:42][CH:43]=[CH:44][C:36]=4[CH3:35])=[CH:24][C:2]=3[Cl:1])=[O:5])[C:7]=2[CH:20]=[CH:19][CH:18]=1
Reactant: Nc1ccc(C(=O)N2Cc3ccccc3Cc3ccccc32)c(Cl)c1
Reactant: Cc1ccccc1C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2Cc3ccccc3Cc3ccccc32)c(Cl)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 81.9 %

Procedure:
A mixture of 0.31 g of 5-(2-chloro-4-amino-benzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine and 0.15 g of N,N-diisopropylethylamine in 10 ml of methylene -5 chloride is cooled in an ice bath while 0.18 g of 2-methylbenzoyl chloride is added. The bath is removed and the reactants stirred at room temperature for 18 hours. The mixture is washed with water, 1N HCl, water, 1M NaHCO3, brine and dried (Na2SO4). The methylene chloride is removed in vacuo to give 0.34 g of the desired product as crystalline solid, m.p. 138°-150° C. M+ =467.
Reaction SMILES: [F:1][C:2]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-])=O)[CH:6]=1)([F:4])[CH3:3].C(N)CN>CO.[Pd]>[F:1][C:2]([C:5]1[CH:6]=[C:7]([CH:8]=[CH:9][CH:10]=1)[NH2:11])([F:4])[CH3:3]
Reactant: CC(F)(F)c1cccc([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CO
Solvent: NCCN
Product: CC(F)(F)c1cccc(N)c1
Reaction time: 5.5 h
Yield: 95.3 %

Procedure:
To a solution of 1-(1,1-difluoroethyl)-3-nitrobenzene (1.00 g, 5.34 mmol) in methanol (5.0 mL) was added Pd/C (catalytic amount) and ethylene diamine (catalytic amount). The reaction mixture was subjected for hydrogenation in Parr apparatus under 30 psi for 5-6 h. The excess of solvent was removed under vacuum to afford 0.800 g of the desired product. 1HNMR (DMSO-d6): δ 1.88 (d, J=18.0 Hz, 3H), 3.74 (s, 1H), 7.72 (t, J=8.4 Hz, 1H), 6.81 (s, 1H), 6.87 (d, J=7.8 Hz, 1H), 7.19 (t, J=7.8 Hz, 1H).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].O.[Br:7][C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][C:9]=1[Cl:15]>N1C=CC=CC=1>[Br:7][C:8]1[CH:14]=[CH:13][C:11]([NH:12][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][C:9]=1[Cl:15]
Reactant: Nc1ccc(Br)c(Cl)c1
Reactant: CS(=O)(=O)Cl
Solvent: O
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc(Br)c(Cl)c1
Reaction time: 1.5 h

Procedure:
In a 100 mL round bottomed flask 4-bromo-3-chloroaniline (A, 2.06 g, 10.0 mmol) was dissolve in pyridine (30 mL) at room temperature. Methanesulfonyl chloride (1.72 g, 15.0 mmol, 1.5 equiv) was added under an ice-water bath cooling. The ice bath was removed immediately after addition of the reagent. After stirring for 1.5 h, another methanesulfonyl chloride (0.57 g, 5.0 mmol, 0.5 equiv) was added at room temperature for the reaction to go to completion. After stirring for 0.5 h, the mixture was treated with H2O (50 mL) and extracted with EtOAc (50 mL×3). Combined organic layers were washed with brine (50 mL×2) and dried over Na2SO4. The solvent was removed in vacuo to give the crude material (very light brown solid, 5.32 g). The crude product was purified by a silica gel column chromatography (SiO2=80 g, EtOAc/hexane=1:1, Rf=0.3) to give the desired product as colorless crystals. The obtained crystals were recrystallized from EtOAc/hexane=1:2 (24 mL) to give the desired material [N-(4-bromo-3-chlorophenyl)methanesulfonamide (B)].
Reaction SMILES: [CH3:1][N:2]([CH3:15])[C:3]([CH:5]1[S:10][C:9]2[S:11][CH:12]=[CH:13][C:8]=2[C:7](=O)[CH2:6]1)=O>O1CCCC1>[CH3:15][N:2]([CH2:3][CH:5]1[S:10][C:9]2[S:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6]1)[CH3:1]
Reactant: CN(C)C(=O)C1CC(=O)c2ccsc2S1
Solvent: C1CCOC1
Product: CN(C)CC1CCc2ccsc2S1
Reaction time: 3 h
Yield: 85.1 %

Procedure:
To a stirred, refluxing solution of N,N-dimethyl-4-oxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-6-carboxamide (7.57 g, 0.0314 mol) under nitrogen in tetrahydrofuran (150 ml) was added dropwise over 10 minutes borane-dimethylsulfide complex (9.4 ml, 0.094 mol). Stirring at reflux was continued for 3 hours and 6NHCl (25 ml) was added dropwise and reflux was continued for 1/2 hour. Most of the tetrahydrofuran was removed in vacuo and the residue was diluted with 6NHCl (50 ml) and was heated for 1/2 hour at steam bath temperature under nitrogen. The mixture was cooled in ice and water (100 ml) was added to dissolve the solid, washed with ether (50 ml) and basified with 10N NaOH (75 ml). The product was extracted into ethyl acetate (200 ml) in four portions, washed with water and dried over Na2SO4. The solution was filtered and concentrated in vacuo to obtain an amber oil (5.7 g). Yield was 85%.
Reaction SMILES: [C:1]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([N+:14]([O-])=O)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)([CH3:4])([CH3:3])[CH3:2]>[Ni]>[C:1]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH2:14])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)n1ccc2cc([N+](=O)[O-])ccc21
Agent: [Ni]
Product: CC(C)(C)n1ccc2cc(N)ccc21
Temperature: 30 °C
Reaction time: 1 h
Yield: 44.3 %

Procedure:
To a solution of 1-tert-butyl-5-nitro-1H-indole (6.5 g, 0.030 mol) MeOH (100 mL) was added Raney Nickel (0.65 g, 10%) under N2 protection. The mixture was stirred under hydrogen atmosphere (1 atm) at 30° C. for 1 h. The catalyst was filtered off and the filtrate was concentrated under vacuum to dryness. The residue was purified by column chromatography on silica gel (PE/EtOAc 1:2) to give 1-tert-butyl-1H-indol-5-amine (2.5 g, 45%). 1H-NMR (CDCl3, 400 MHz) δ 7.44 (d, J=8.8 Hz, 1H), 7.19 (dd, J=3.2 Hz, 1H), 6.96 (d, J=2.0 Hz, 1H), 6.66 (d, J=2.0, 8.8 Hz, 1H), 6.26 (d, J=3.2 Hz, 1H), 1.67 (s, 9H). MS (ESI) m/e (M+H+) 189.2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Cl-].[Al+3].[Cl-].[Cl-].[C:18](Cl)(=[O:20])[CH3:19].Cl>C(=S)=S>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]([C:18](=[O:20])[CH3:19])=[CH:12][CH:13]=1
Reactant: CC(=O)Cl
Reactant: Fc1ccccc1-c1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: CC(=O)c1ccc(-c2ccccc2F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 200 g of 2-fluorobiphenyl in 1500 ml of carbon disulfide was cooled to 0°-5°C and successively treated with 200 g of aluminum chloride over a period of 140 minutes and 113 g of acetyl chloride over a period of 165 minutes. The resulting mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture then was poured carefully into a mixture of ice and aqueous hydrochloric acid. Organic materials were extracted from the resulting acidic mixture with a mixture of diethyl ether and ethyl acetate. The organic extract was washed successively with water, ten percent aqueous sodium hydroxide, and water, and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure and the solid residue was recrystallized from hexane to give 4'-(2-fluorophenyl)-acetophenone. Recrystallization of the material from hexane gave two crops of crystals having the following elemental analyses:
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1/[C:6](=[N:24]/[O:25][CH3:26])/[C:7]([NH:9][C@@H:10]1[C:22](=[O:23])[N:12]2[C:13]([C:19]([OH:21])=[O:20])=[C:14]([CH2:17][OH:18])[CH2:15][S:16][C@H:11]12)=[O:8].[N-:27]=[C:28]=[O:29]>O1CCOCC1>[CH3:26][O:25]/[N:24]=[C:6](\[C:7]([NH:9][C@@H:10]1[C:22](=[O:23])[N:12]2[C:13]([C:19]([OH:21])=[O:20])=[C:14]([CH2:17][O:18][C:28]([NH2:27])=[O:29])[CH2:15][S:16][C@H:11]12)=[O:8])/[C:2]1[O:1][CH:5]=[CH:4][CH:3]=1
Reactant: CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(CO)CS[C@H]12)c1ccco1
Reactant: [N-]=C=O
Solvent: C1COCCO1
Product: CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@H]12)c1ccco1
Yield: 77 %

Procedure:
A solution of (6R,7R)-7-[Z-2-(fur-2-yl)-2-methoxyiminoacetamido]-3-hydroxymethyl-ceph-3-em-4-carboxylic acid (3.84 g) in dioxan (35 ml) was added to the above isocyanate solution at ca 25°. The reaction and work up was similar to that described in Example 8, except that the product was not triturated with ether, and yielded the title compound as a pale yellow solid, (3.28 g, 77%) m.p. (M802)179°; [α]D22 +54.4° (c.1.0, DMSO).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:22]=[CH:21][C:9]3[C:10]4[N:11]=[C:12]([C:18]([OH:20])=O)[S:13][C:14]=4[CH2:15][CH2:16][O:17][C:8]=3[CH:7]=2)[CH:3]=[N:2]1.CN(C)C=O.C(NC(C)C)(C)C.[CH:35]([NH:38][CH2:39][CH2:40][OH:41])([CH3:37])[CH3:36]>>[OH:41][CH2:40][CH2:39][N:38]([CH:35]([CH3:37])[CH3:36])[C:18]([C:12]1[S:13][C:14]2[CH2:15][CH2:16][O:17][C:8]3[CH:7]=[C:6]([C:4]4[CH:3]=[N:2][NH:1][CH:5]=4)[CH:22]=[CH:21][C:9]=3[C:10]=2[N:11]=1)=[O:20]
Reactant: CC(C)NCCO
Reactant: O=C(O)c1nc2c(s1)CCOc1cc(-c3cn[nH]c3)ccc1-2
Solvent: CN(C)C=O
Solvent: CC(C)NC(C)C
Product: CC(C)N(CCO)C(=O)c1nc2c(s1)CCOc1cc(-c3cn[nH]c3)ccc1-2
Temperature: 50 °C
Yield: 15.1 %

Procedure:
To a solution of 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (363.8 mg, 1.161 mmol) in N,N-dimethylformamide (39-60 equiv.) and N,N-Diisopropylamine (1.5 equiv.) was added 2-(isopropylamino)ethanol (133.1 mg, 1.29 mmol) followed by the addition of N,N,N′N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uranium hexafluorophosphate (1.1 equiv.). The reaction mixture was heated at 50° C. for 2 hrs to 24 hours depending on when complete by LCMS. Reaction mixture was concentrated on the genevac and purified by HPLC or diluted with ethyl acetate, washed with brine, dried over sodium sulfate and concentrated in vacuo prior to purification by HPLC to give 103 (70 mg, 15% yield, M+1 399.1)