Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@@H]2N1CCC2.[CH3:22][O:23][C:24]([C:26]1[CH:35]=[CH:34][C:33]2[C:32](=[O:36])[CH2:31][CH2:30][CH2:29][C:28]=2[CH:27]=1)=[O:25].CO>C1(C)C=CC=CC=1.C1COCC1>[OH:36][C@H:32]1[CH2:31][CH2:30][CH2:29][C:28]2[CH:27]=[C:26]([C:24]([O:23][CH3:22])=[O:25])[CH:35]=[CH:34][C:33]1=2
Reactant: COC(=O)c1ccc2c(c1)CCCC2=O
Agent: CB1OC(c2ccccc2)(c2ccccc2)[C@H]2CCCN12
Solvent: CO
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc2c(c1)CCC[C@@H]2O
Temperature: -10 °C

Procedure:
To an oven-dried 2 L round-bottomed flask equipped with an argon inlet/outlet and magnetic stirring was added (R)-2-methyl-CBS-oxazaborolidine (7.4 mL of a 1M solution in toluene, 7.4 mmol, Aldrich). Toluene (190 mL) was added and the reaction mixture was cooled in an ice-salt bath (bath temp.=−10° C.). BH3—SMe2 was added (17 mL, 180 mmol, Aldrich), then 5-oxo-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid methyl ester (30 g, 150 mmol, Albany Molecular) in 200 mL of THF was added over 5 h using a syringe pump. After the addition was complete, the reaction mixture was stirred for an additional 1 h. The reaction mixture was poured into an addition funnel, and then added to 200 mL of MeOH, cooled in a ice-salt bath, over 30 min at such a rate that the internal temperature was kept below 0° C. The mixture was concentrated in vacuo. Et2O (1 L) was added, and the mixture was washed with 1M H3PO4 (3×), 5% NaHCO3, and brine (ca. 400 mL each wash). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was dissolved in Et2O again (500 mL), and the mixture was washed with 1M H3PO4 (3×200 mL), satd NaHCO3, and brine. After drying the organic layer over MgSO4, the mixture was filtered and concentrated in vacuo, which gave the title compound as a white-yellow solid. MS (+ion ESI) m/z =207 (MH+), 189 (MH+-H2O).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[C:7](=O)[O:6][C:5]2=[O:13].[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21]C(O)=O)=[CH:17][C:16]=1[C:25]([N:27]1[CH2:32][CH2:31][CH:30]([O:33][CH3:34])[CH2:29][CH2:28]1)=[O:26].C([O-])(=O)C.[Na+].[Al]>>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4](=[CH:3][C:2]=1[Cl:1])[C:5](=[O:13])[O:6]/[C:7]/2=[CH:21]\[C:18]1[CH:19]=[CH:20][C:15]([F:14])=[C:16]([C:25]([N:27]2[CH2:32][CH2:31][CH:30]([O:33][CH3:34])[CH2:29][CH2:28]2)=[O:26])[CH:17]=1
Reactant: O=C1OC(=O)c2cc(Cl)c(Cl)cc21
Reactant: COC1CCN(C(=O)c2cc(CC(=O)O)ccc2F)CC1
Agent: CC(=O)[O-]
Agent: [Al]
Agent: [Na+]
Product: COC1CCN(C(=O)c2cc(/C=C3\OC(=O)c4cc(Cl)c(Cl)cc43)ccc2F)CC1
Temperature: 240 °C
Reaction time: 1 h
Yield: 16.9 %

Procedure:
A flask charged with 5,6-dichloroisobenzofuran-1,3-dione (370 mg, 1.71 mmol), 2-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl)acetic acid (43) (496 mg, 1.68 mmol) and Sodium acetate (34 mg, 0.41 mmol) was lowered into a pre-heated aluminium block at 210° C. The resulting mixture was heated further and stirred at 240° C. for 1 hour then cooled. The residue was triturated, with sonication, under ethanol (˜25 mL) and solid collected by suction filtration to afford crude product (128 mg, 16.92%), which was used directly without further purification; m/z (LC-MS, ESI+), RT=2.79 (M+H 450.1 & 452.0).
Reaction SMILES: [NH2:1][C:2]1[C:7]2=[CH:8][CH:9]=[C:10]([C:11]3[N:12]=[C:13]([CH:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[S:14][CH:15]=3)[N:6]2[N:5]=[CH:4][N:3]=1.[Br:29]N1C(C)(C)C(=O)N(Br)C1=O>CN(C=O)C.CC(O)=O>[NH2:1][C:2]1[C:7]2=[C:8]([Br:29])[CH:9]=[C:10]([C:11]3[N:12]=[C:13]([CH:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[S:14][CH:15]=3)[N:6]2[N:5]=[CH:4][N:3]=1
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Reactant: CC(C)(C)OC(=O)N1CCC(c2nc(-c3ccc4c(N)ncnn34)cs2)CC1
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(c2nc(-c3cc(Br)c4c(N)ncnn34)cs2)CC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 109.1 %

Procedure:
To a cooled (−20° C.) solution of tert-butyl 4-[4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate (914 mg. 2.28 mmol) in DMF (12.6 mL) and AcOH (5 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (326 mg, 1.14 mmol) in 3 portions over 10 minutes. The mixture was stirred at 0° C. for 3 h. The reaction was quenched with the addition 5% aqueous K2CO3 (50 mL) and was allowed to warm to rt. The mixture was extracted with ethyl acetate (3×50 mL). The combined organics were washed with brine, dried (Na2SO4) and evaporated. The crude material was purified by ISCO® chromatography using a gradient of 50% to 75% ethyl acetate in hexanes to afford 596 mg (54%) of the desired product. ES-MS m/z 480.85 [M+H]+, HPLC RT (min) 3.45.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[N:16]=[C:15]([CH2:17][C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])[C:14]([CH2:26][NH:27][S:28]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=3)(=[O:30])=[O:29])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CO.[C:41]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.C(OCC)(=O)C.CCCCCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[N:16]=[C:15]([CH2:17][C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])[C:14]([CH2:26][N:27]([CH3:41])[S:28]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=3)(=[O:30])=[O:29])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: N#Cc1cccc(S(=O)(=O)NCc2ccc(S(=O)(=O)c3ccc(Cl)cc3)nc2Cc2cc(F)ccc2F)c1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CO
Product: CN(Cc1ccc(S(=O)(=O)c2ccc(Cl)cc2)nc1Cc1cc(F)ccc1F)S(=O)(=O)c1cccc(C#N)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 56.8 %

Procedure:
To a solution of N-[[6-(4-chlorophenylsulfonyl)(2,5-difluorophenyl)methylpyridin-3-yl]methyl]-3-cyanobenzenesulfonamide (21 mg, 0.037 mmol) in tetrahydrofuran (0.5 ml) were successively added methanol (0.003 ml, 0.073 mmol), triphenylphosphine (19 mg, 0.073 mmol) and diisopropyl azodicarboxylate (0.014 ml, 0.073 mmol) at 0° C. The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel chromatography. A fraction obtained from the elution portion with hexane:ethyl acetate=2:1 was concentrated under reduced pressure, whereby the title compound (13 mg, 0.021 mmol, 58%) was obtained as a white solid.
Reaction SMILES: [BH4-].[Na+].[N:3]([CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[NH:26])[NH:15][C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:10][CH2:9]1)=[N+]=[N-].Cl>O.O1CCCC1.[Pd]>[NH2:3][CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[NH:26])[NH:15][C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[CH2:10][CH2:9]1
Reactant: [N-]=[N+]=NCCC1CCN(C(=N)NC(=O)OCc2ccccc2)CC1
Agent: [Pd]
Agent: Cl
Agent: [BH4-]
Solvent: O
Solvent: C1CCOC1
Product: N=C(NC(=O)OCc1ccccc1)N1CCC(CCN)CC1
Temperature: 0 °C

Procedure:
To 30 ml of water was added 0.40 g of 10% Pd/C. Sodium borohydride, 1.0 g (0.031 mol), was dissolved in 30 ml of water and was added carefully to the stirred and ice-cooled slurry of Pd/C and water. 4-Azidoethyl-1-benzyloxycarbonylamidino piperidine, 2.9 g (8.8 mmol), was dissolved in 80 ml of tetrahydrofurane and this solution was added dropwise to the ice-cooled aqueous slurry above. After 4 h of stirring at room temperature the mixture was ice-cooled again and 30 ml of 2M HCl was added. The mixture was filtered through celite and the celite was rinsed with additional water. The tetrahydrofuran was evaporated and the aqueous phase was washed with ethyl acetate. The aqueous phase was made alkaline with 2M NaOH and extracted with methylene chloride three times. The combined organic phase was washed with water, dried (Na2SO4) and evaporated. The product was used in the following step without further purification.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4](O)[CH2:3]1.[NH:13]1[CH:17]=[CH:16][N:15]=[CH:14]1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CN(C)C(N=NC(N(C)C)=O)=O>C1(C)C=CC=CC=1.CCCCCCC>[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]([N:13]2[CH:17]=[CH:16][N:15]=[CH:14]2)[CH2:3]1
Reactant: c1c[nH]cn1
Reactant: CC1(C)CC(O)c2ccccc21
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CN(C)C(=O)N=NC(=O)N(C)C
Solvent: CCCCCCC
Solvent: Cc1ccccc1
Product: CC1(C)CC(n2ccnc2)c2ccccc21
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of 3,3-dimethyl-indan-1-ol (CAS#38393-92-9, 1.62 g, 1.0 mmol)] in toluene (30 mL) is added imidazole (1.36 g, 20.0 mmol) followed by tri-t-butylphosphine (2.5 mL, 10.1 mmol). The reaction is put at 0° C. and N,N,N′,N′-tetramethylazodicarboxamide (1.72 g, 10 mol) is then added. The reaction is permitted to stir for 10 minutes at 0° C. and then is heated at 60° C. over night. The next morning the reaction is diluted with heptane (30 mL) and filtered. The filtrate is extracted twice with 1 N aqueous HCl. The aqueous extracts are combined, washed with ethyl acetate and then basified (pH>10) by the careful addition of 5 N aqueous NaOH. The aqueous solution is then extracted three times with dichloromethane. The combined organic extracts are dried with Na2SO4. filtered and concentrated. The resulting residue is purified by semi-preparative reverse phase HPLC (15 to 85% acetonitrile/water w/0.1% NH4OH) to afford 1-(3,3-dimethyl-indan-1-yl)-1H-imidazole; HRMS: (ESI) m/z 213.1397 [(M+H)+; calcd for C14H17N2: 213.1392]; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 3 H), 1.42 (s, 3 H), 2.11 (dd, J=12.9, 8.3 Hz, 1 H), 2.57 (dd, J=12.9, 7.6 Hz, 1 H), 5.72 (t, J=8.1 Hz, 1 H), 6.86 (s, 1 H), 7.01 (d, J=8.3 Hz, 1 H), 7.09 (s, 1 H), 7.19-7.29 (m, 2 H), 7.35 (t, J=7.5 Hz, 1 H), 7.62 (s, 1 H). The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 1-(3,3-dimethyl-indan-1-yl)-1H-imidazole.
Reaction SMILES: O.C([NH:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[N:50][O:51][CH:52]([F:54])[F:53])[C:28]([NH:30][CH:31]2[C:48](=[O:49])[N:33]3[C:34]([C:45]([OH:47])=[O:46])=[C:35]([CH2:38][S:39][C:40]4[S:41][CH:42]=[N:43][N:44]=4)[CH2:36][S:37][C@H:32]23)=[O:29])[N:26]=1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>C(O)=O>[NH2:21][C:22]1[S:23][CH:24]=[C:25]([C:27](=[N:50][O:51][CH:52]([F:53])[F:54])[C:28]([NH:30][CH:31]2[C:48](=[O:49])[N:33]3[C:34]([C:45]([OH:47])=[O:46])=[C:35]([CH2:38][S:39][C:40]4[S:41][CH:42]=[N:43][N:44]=4)[CH2:36][S:37][C@H:32]23)=[O:29])[N:26]=1
Reactant: O=C(O)C1=C(CSc2nncs2)CS[C@@H]2C(NC(=O)C(=NOC(F)F)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)C(=O)N12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: O=CO
Solvent: CCOC(C)=O
Product: Nc1nc(C(=NOC(F)F)C(=O)NC2C(=O)N3C(C(=O)O)=C(CSc4nncs4)CS[C@H]23)cs1
Reaction time: 4 h
Yield: 64 %

Procedure:
Water (2.7 ml) was added to a stirred solution of 7-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (0.9 g) in formic acid (9 ml) at 7° C. under ice-cooling and the mixture was stirred at the same temperature for 4 hours. The reaction mixture was poured into a mixture of water (150 ml) and ethyl acetate (50 ml) and adjusted to pH 2.5 with an aqueous solution of sodium bicarbonate. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo to give 7-[2-(2-aminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (0.4 g).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]4[O:15][CH2:16][CH2:17][C:11]=4[N:10]3[C:18]=2[CH2:19][C:20]#[N:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:29](Cl)(=[O:31])[CH3:30]>N.C(O)C.C(=O)([O-])O.[Na+].[Co]>[C:1]1([C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]4[O:15][CH2:16][CH2:17][C:11]=4[N:10]3[C:18]=2[CH2:19][CH2:20][NH:21][C:29](=[O:31])[CH3:30])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: N#CCc1c(-c2ccccc2)nc2ccc3c(n12)CCO3
Reactant: CC(=O)Cl
Agent: [Co]
Agent: N
Agent: O=C([O-])O
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(=O)NCCc1c(-c2ccccc2)nc2ccc3c(n12)CCO3
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 64.7 %

Procedure:
To a solution (5 mL) of (7-phenyl-1,2-dihydrofuro[2,3-e]imidazo[1,2-a]pyridin-8-yl)acetonitrile (17.0 mg, 0.062 mmol) in 2M ammonia/ethanol was added Raney cobalt (500 mg), and the mixture was stirred at room temperature for 2.5 hr under a hydrogen atmosphere. The catalyst was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (2 mL), triethylamine (17.3 μL, 0.124 mmol) and acetyl chloride (5.3 μL, 0.074 mmol) were added, and the mixture was stirred at room temperature for 20 min. The reaction solution was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) and recrystallization (ethyl acetate/hexane) to give the title compound (12.9 mg, yield 65%).
Reaction SMILES: C1(P(=[N:20][C:21]2[CH:25]=[CH:24][S:23][C:22]=2[CH:26]=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:28]([O:36][CH2:37][CH3:38])(=[O:35])[CH2:29][C:30]([O:32][CH2:33][CH3:34])=O.N1CCCCC1>CCO>[CH2:33]([O:32][C:30]1[N:20]=[C:21]2[CH:25]=[CH:24][S:23][C:22]2=[CH:26][C:29]=1[C:28]([O:36][CH2:37][CH3:38])=[O:35])[CH3:34]
Reactant: O=Cc1sccc1N=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)CC(=O)OCC
Solvent: CCO
Solvent: C1CCNCC1
Product: CCOC(=O)c1cc2sccc2nc1OCC

Procedure:
A solution of 3-[(triphenylphosphoranylidene)amino]-2-thiophenecarbaldehyde (11-2, 2.50 g, 6.45 mmol, 1 equiv), diethyl malonate (1.96 mL, 12.9 mmol, 2.00 equiv), and piperidine (0.319 mL, 3.23 mmol, 0.500 equiv) in EtOH (50 mL) was heated at reflux for 16 h. The reaction mixture was concentrated, and the residue was purified by flash column chromatography (heaxane, initally, grading to 30% EtOAc in hexane) to give ethyl 5-ethoxythieno[3,2-b]pyridine-6-carboxylate (11-3) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.64 (s, 1H), 7.84 (d, 1H, J=7.4 Hz), 7.37 (d, 1H, J=7.2 Hz), 4.55 (q, 2H, J=7.0 Hz), 4.40 (q, 2H, J=7.1 Hz), 1.48 (t, 3H, J=7.0 Hz), 1.41 (t, 3H, J=7.1 Hz).
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH2:11]([N:13](C(C)C)C(C)C)C.O>ClCCl.O1CCCC1>[O:1]1[C:5]2([CH2:10][CH2:9][N:8]([C:11]#[N:13])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1
Reactant: C1CC2(CCN1)OCCO2
Reactant: CCN(C(C)C)C(C)C
Solvent: O
Solvent: C1CCOC1
Solvent: ClCCl
Product: N#CN1CCC2(CC1)OCCO2
Temperature: 25 °C

Procedure:
Bromonitrile (11.12 g) is added to a mixture of 1,4-dioxa-8-aza-spiro[4.5]decane (10.00 g) and ethyldiisopropylamine (59.92 mL) in dichloromethane (125 mL) and tetrahydrofuran (125 mL). The reaction mixture is stirred over night at room temperature. Water is added and the organic phase is separated, dried over Na2SO4 and concentrated in vacuo to give the title compound. TLC: rf=0.80 (aluminum oxide, ethyl acetate/petrol ether 3:1); Mass spectrum (ESI+): m/z=169 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[CH:27]=[CH:26][N:25]([CH3:28])[N:24]=3)=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:35].[Na+].O1CCCC1>CO.C(#N)C>[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:35])[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[CH:27]=[CH:26][N:25]([CH3:28])[N:24]=3)=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: [BH3-]C#N
Reactant: CC(=O)c1cc(Cl)c2cccnc2c1N1CCN(C(=O)c2ccn(C)n2)CC1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CC#N
Product: CC(N)c1cc(Cl)c2cccnc2c1N1CCN(C(=O)c2ccn(C)n2)CC1
Temperature: 65 °C

Procedure:
A mixture of 1-(5-chloro-8-{4-[(1-methyl-1H-pyrazol-3-yl)carbonyl]piperazin-1-yl}quinolin-7-yl)ethanone (0.032 g, 0.080 mmol) and ammonium acetate (0.0620 g, 0.804 mmol) in methanol (0.3 mL,) and acetonitrile (0.3 mL) was heated at 65° C. in a sealed tube for 1 hour. After cooling to room temperature, to the resulting mixture was added 1.0 M sodium cyanoborohydride in tetrahydrofuran (0.20 mL, 0.20 mmol). The reaction was heated at 65° C. overnight. The mixture was cooled to room temperature, quenched with sat. NaHCO3 solution, extracted with dichloromethane, dried over MgSO4 and concentrated to give the crude product. LCMS calculated for C20H24ClN6O (M+H)+: m/z=399.2; Found: 399.2.
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4]1.C(N(CC)CC)C.[CH3:24][S:25](Cl)(=[O:27])=[O:26]>C(Cl)Cl>[CH3:24][S:25]([O:1][CH2:2][C@H:3]1[O:7][C:6](=[O:8])[N:5]([NH:9][C:10]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:16])[CH2:4]1)(=[O:27])=[O:26]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)NN1C[C@H](CO)OC1=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NN1C[C@@H](COS(C)(=O)=O)OC1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 93.9 %

Procedure:
To a turbid solution of (R)-tert-butyl 5-(hydroxymethyl)-2-oxooxazolidin-3-ylcarbamate (840 mg, 3.62 mmol) in DCM (10 mL), triethylamine (458 mg, 4.52 mmol) and methanesulfonyl chloride (518 mg, 4.52 mmol) were added and the reaction was stirred, at r.t., under nitrogen, for 2 h 30 min. The solution was washed with: cold water (resulting pH=7-8), cold citric acid (resulting pH=4-5) and cold brine. The organic layer was dried over Na2SO4 and evaporated and the residue (beige foam) was triturated with diisopropyl ether, affording (S)-(3-(tert-butoxycarbonylamino)-2-oxooxazolidin-5-yl)methyl methanesulfonate (1.055 g, 3.40 mmol) as a white solid, that was dissolved in 7 mL of DMF. Sodium methanethiolate (317 mg, 4.52 mmol) was added to the solution and the mixture was stirred at 60° C. for 3 h. AcOEt was added and the solution was washed with cold water, cold citric acid (until pH=6) and cold brine. The organic layer was dried over Na2SO4 and evaporated to leave a yellow oil. The title compound was precipitated by crystallization from diisopropyl ether as a white solid, recovered by filtration on Buchner (429 mg, 1.635 mmol). Yield=45%.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]=1[C:20](O)=[O:21].C(OCC)(=O)C.O>O1CCCC1>[CH3:7][C:8]1[C:9]([CH2:20][OH:21])=[C:10]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:11]=[CH:12][CH:13]=1
Reactant: Cc1cccc(-c2ccccc2)c1C(=O)O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: Cc1cccc(-c2ccccc2)c1CO
Temperature: 25 °C
Reaction time: 17 h
Yield: 84.6 %

Procedure:
To an ice-cooling suspension of lithium aluminium hydride (1.79 g) in tetrahydrofuran (50 ml) was added dropwise a solution of 4,-methylbiphenyl-2-carboxylic acid (5.0 g) in tetrahydrofuran (30 ml). The mixture was stirred for 17 hours at room temperature. To the reaction mixture were added ethyl acetate (10 ml) and water (50 ml), and insoluble materials were removed by filtration through celite. The filtrate was concentrated to dryness, and the residue was dissolved in ethyl acetate. The solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and dried. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel to afford the title compound as colorless syrup (3.95 g, 84%).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.C([N-]C(C)C)(C)C.[Li+].[CH2:21]([NH:28][C:29](=[O:37])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH3:36])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CON(C)[C:41](=O)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C1COCC1.CCCCCC>[CH2:21]([N:28]1[C:41]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[CH:36][C:31]2[C:30](=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:29]1=[O:37])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: Cc1ccccc1C(=O)NCc1ccccc1
Reactant: CON(C)C(=O)c1ccccc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: O=c1c2ccccc2cc(-c2ccccc2)n1Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 11 %

Procedure:
To a solution of diisopropylamine (0.2 mL, 1.43 mmol) in THF (3 mL) at 0° C. was added n-butyllithium (0.9 mL of a 1.6 M solution in hexane, 1.44 mmol). After stirring at 0° C. for 10 minutes, the resulting lithium diisopropylamide solution was treated with a solution of N-benzyl-2-methylbenzamide (145 mg, 0.64 mmol) in THF (2 mL). The resulting deep purple solution was stirred at 0° C. for 75 minutes at which time it was treated with a solution of N-methoxy-N-methyl-benzamide (117 mg, 0.71 mmol) in THF (2 mL). After slowly warming to ambient temperature over 100 minutes the reaction was quenched by the addition of 3N HCl (12 mL). The biphasic mixture was then heated to reflux with vigorous stirring. After 1 hour at reflux the reaction mixture was allowed to cool to ambient temperature. After cooling, the reaction was diluted with ether (50 mL), and basified by careful addition of solid Na2CO3. The basic aqueous was extracted with ether (3×20 mL), combined organics were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated under educed pressure to afford a pale orange oil. The crude product was purified by silica gel column chromatography eluting with a gradient from 0% to 20% ethyl acetate/hexane on a 20 g silica column. The product peak was collected to afford 2-benzyl-3-phenyl-2H-isoquinolin-1-one (22 mg, 11% yield) as a clear oil that slowly solidified to a white waxy solid. 1H-NMR (400 MHz, CDCl3): δ 8.49 (1H, d J=8.3 Hz), 7.68-7.63 (1H, m), 7.53-7.48 (2H, m), 7.42-7.37 (1H, m), 7.35-7.30 (2H, m), 7.22-7.14 (5H, m), 6.92-6.88 (2H, m), 6.45 (1H, s), 5.25 (2H, s) ppm.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[OH:12].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C=O)C>[CH2:19]([O:12][C:3]1[CH:4]=[C:5]([N+:9]([O-:11])=[O:10])[C:6]([F:8])=[CH:7][C:2]=1[Br:1])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=[N+]([O-])c1cc(O)c(Br)cc1F
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc(OCc2ccccc2)c(Br)cc1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 2-bromo-4-fluoro-5-nitro-phenol (3.5 g, 14.83 mmol) and Cs2CO3 (5.80 g, 17.80 mmol) in DMF (26 mL) was added benzyl bromide (2.80 g, 1.94 mL, 16.31 mmol) dropwise. The reaction was stirred at room temperature under an inert atmosphere for 2 h. The reaction was quenched with water and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography using 40% DCM/hexane gradient to yield 1-(benzyloxy)-2-bromo-4-fluoro-5-nitrobenzene. 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J=6.4 Hz, 1H), 7.59 (d, J=9.9 Hz, 1H), 7.52-7.34 (m, 5H), 5.23 (s, 2H).