Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([OH:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[CH:13][CH2:14][CH3:15].[C:17](Cl)(=[O:21])[C:18]([CH3:20])=[CH2:19].C(N(CC)CC)C>C(Cl)Cl>[C:17]([O:16][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[CH:13][CH2:14][CH3:15])(=[O:21])[C:18]([CH3:20])=[CH2:19]
Reactant: C=C(C)C(=O)Cl
Reactant: CCC=CCCCCCCCCCCCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=C(C)C(=O)OCCCCCCCCCCCC=CCC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Pentadeca-12-ene-1-ol (22.6 grams) is placed in a three-neck flask under a blanket of nitrogen. The entire reaction contents are cooled in an ice bath. Methacryloyl chloride (10.5 grams) dissolved in about 50 mL of methylene chloride is added slowly to the cooled pentadeca-12-ene-1-ol with vigorous stirring in about 2 hours. Triethylamine (11.5 g) dissolved in 25 mL of methylene chloride is subsequently added in about an hour. After addition of triethylamine, the solution is allowed to warm to ambient temperature and is stirred for another 4 hours in order to complete the reaction. The precipitated triethylammonium chloride is removed by filtration, and the filtrate is washed with brine solution (saturated NaCI) followed by washings with dil. NaOH and dil. HCl. The organic layer is dried with anhydrous magnesium sulfate and the solvent is removed in vacuo to yield pentadeca-12-ene-1-yl methacrylate in good yields. Pentadeca-12-ene-1-yl methacrylate is stabilized from polymerization by addition of approximately 10 ppm hydroquinone. The structure of the product is verified by 1H and 13C NMR spectroscopy.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH2:27])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].Br[C:29]1[CH:34]=[N:33][CH:32]=[C:31]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:30]=1>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:29]4[CH:34]=[N:33][CH:32]=[C:31]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[N:30]=4)=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4N)cc3)cc2)CC1
Reactant: Brc1cncc(-c2ccccc2)n1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cncc(-c5ccccc5)n4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 41, Step 2, using 1-[4′-(4-amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and 2-bromo-6-phenyl-pyrazine.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[CH2:12][C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=[O:4].[CH3:23][Al](C)C.C[Zn]C.CCCCCCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([OH:20])([CH3:23])[CH2:12][C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=[O:4]
Reactant: COC(=O)c1cncn1C1c2ccccc2C(=O)CC1(C)C
Reactant: C[Al](C)C
Agent: C[Zn]C
Solvent: Cc1ccccc1
Solvent: CCCCCCC
Product: COC(=O)c1cncn1C1c2ccccc2C(C)(O)CC1(C)C
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a solution of 3-(2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester, which can be prepared as described in Example 13, (985 mg, 3.31 mmol) in toluene (35 mL) at −78° C. is added a 2.0 M solution of trimethyl aluminum in toluene (3.3 mL, 6.6 mmol) followed by a 1.0 M solution of dimethyl zinc in heptane (6.6 mL, 6.6 mmol). The reaction is allowed to warm to room temperature and stirred for approximately 48 hours. The reaction is then quenched with saturated aqueous NH4Cl, and diluted with saturated aqueous NaHCO3. The reaction mixture is then extracted with dichloromethane. The organic extract is dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (diethylamine-methanol-dichloromethane, 1:2:97) to furnish 3-(4-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester as a single diastereomer; MS: (ESI) m/z 315 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (s, 3 H), 1.04 (s, 3 H), 1.59 (br. s., 1 H), 1.65 (s, 3 H), 1.95-2.18 (m, 2 H), 3.90 (s, 3 H), 6.44 (s, 1 H), 6.76 (d, J=7.8 Hz, 1 H), 7.16-7.25 (m, 1 H), 7.37 (t, J=7.6 Hz, 1 H), 7.46 (s, 1 H), 7.66 (d, J=7.8 Hz, 1 H), 7.83 (s, 1 H);
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:20]=[CH:19][C:8]([O:9][C:10]2[S:11][C:12]3[C:13]([N:18]=2)=[N:14][CH:15]=[CH:16][CH:17]=3)=[CH:7][CH:6]=1.[NH:21]1[CH2:26][CH2:25][CH:24]([O:27][C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[CH2:23][CH2:22]1.C(N(CC)C(C)C)(C)C>CC#N>[N:29]1[CH:30]=[CH:31][CH:32]=[N:33][C:28]=1[O:27][CH:24]1[CH2:25][CH2:26][N:21]([CH2:2][CH2:3][O:4][C:5]2[CH:20]=[CH:19][C:8]([O:9][C:10]3[S:11][C:12]4[C:13]([N:18]=3)=[N:14][CH:15]=[CH:16][CH:17]=4)=[CH:7][CH:6]=2)[CH2:22][CH2:23]1
Reactant: c1cnc(OC2CCNCC2)nc1
Reactant: BrCCOc1ccc(Oc2nc3ncccc3s2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: c1cnc(OC2CCN(CCOc3ccc(Oc4nc5ncccc5s4)cc3)CC2)nc1
Temperature: 70 °C
Reaction time: 18 h
Yield: 38.5 %

Procedure:
To a solution of 2-[4-(2-bromoethoxy)phenoxy][1,3]thiazolo[4,5-b]pyridine (131 mg, 0.37 mmol) and 2-(piperidin-4-yloxy)-pyrimidine (80 mg, 0.45 mmol, 1.2 equiv.) in CH3CN (1.9 mL) was added N,N-diisopropylethylamine (97 μL, 0.56 mmol, 1.5 equiv.). The resulting solution was allowed to stir at 70° C. for 18 h. The solution was then cooled to rt, filtered and purified using preparative reverse phase HPLC to afford the desired product as a yellow-brown solid (64 mg, 38%). 1H NMR (600 MHz, CDCl3): 8.58-8.54 (m, 1H), 8.52-8.48 (m, 2H), 8.01-7.96 (m, 1H), 7.34-7.30 (m, 2H), 7.18 (dd, J=6.7, 4.8, 1H), 6.96 (d, J=8.1, 2H), 6.92-6.87 (m, 1H), 5.14-5.04 (m, 1H), 4.14 (t, J=5.6, 2H), 2.96-2.88 (m, 2H), 2.86 (t, J=5.5, 2H), 2.56-2.46 (m, 2H), 2.16-2.04 (m, 2H), 2.01-1.90 (m, 2H). MS (ESI): mass calcd. for C23H23N5O3S, 449.15; m/z found, 450.1 [M+H]+.
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2.[OH:15][C:16]1([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=2)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.[C:33]([OH:38])(=[O:37])[C:34]([OH:36])=[O:35].CO>C(OCC)(=O)C>[C:33]([OH:38])(=[O:37])[C:34]([OH:36])=[O:35].[NH:10]1[C:11]2[C:7](=[C:6]([O:5][CH2:4][C@@H:2]([OH:1])[CH2:3][N:19]3[CH2:20][CH2:21][C:16]([OH:15])([C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:30])([F:32])[F:31])[CH:23]=4)[CH2:17][CH2:18]3)[CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:9]1
Reactant: OC1(c2ccc(Cl)c(C(F)(F)F)c2)CCNCC1
Reactant: c1cc(OC[C@@H]2CO2)c2cc[nH]c2c1
Agent: O=C(O)C(=O)O
Solvent: CO
Solvent: CCOC(C)=O
Product: O[C@H](COc1cccc2[nH]ccc12)CN1CCC(O)(c2ccc(Cl)c(C(F)(F)F)c2)CC1

Procedure:
The title compound was prepared in similar fashion from (S)-(+)-4-(oxiranylmethoxy)-1H-indole and 4-hydroxy-4-(3-trifluoromethyl-4-chlorophenyl)piperidine. The resulting free base was dissolved in ethyl acetate, and precipitated with one equivalent of oxalic acid in ethyl acetate in 85% overall yield. FDMS m/e=469 (M+ of free base). α[D]589 =-11.53 (c=0.54, methanol).
Reaction SMILES: C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)=[CH:6][CH:5]=1.CO.[OH-].[Na+]>C1COCC1>[N:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:20]=[CH:21][C:12]=1[CH2:11][CH2:10][C:7]1[CH:6]=[CH:5][C:4]([C:3]([OH:22])=[O:2])=[CH:9][CH:8]=1
Reactant: COC(=O)c1ccc(CCc2ccc3ccccc3n2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1ccc(CCc2ccc3ccccc3n2)cc1
Reaction time: 4 h
Yield: 85 %

Procedure:
To a solution of 4-(2-Quinolin-2-yl-ethyl)-benzoic acid methyl ester (680 mg) in THF (11 ml)/methanol (3 ml) was added 1N sodium hydroxide solution (4.67 ml). The reaction mixture stirred for 4 h. and the pH adjusted to 3. The white solid was filtered to provide the title compound (550 mg, 86%). MS: (M+H m/z=278.1).
Reaction SMILES: [CH2:1]([Mg]Cl)[CH:2]=[CH2:3].[CH:6]([C:8]1[C@H:13]([C:14]([O:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[N:12]2[C:30](=[O:42])[C@@H:31]([NH:32][C:33](=[O:41])[CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C@H:11]2[S:10][CH:9]=1)=[O:7].[Cl-].[Li+].Cl>O1CCCC1.C(OCC)(=O)C>[OH:7][CH:6]([C:8]1[C@H:13]([C:14]([O:16][CH:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:15])[N:12]2[C:30](=[O:42])[C@@H:31]([NH:32][C:33](=[O:41])[CH2:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[C@H:11]2[S:10][CH:9]=1)[CH2:3][CH:2]=[CH2:1]
Reactant: C=CC[Mg]Cl
Reactant: O=CC1=CS[C@@H]2[C@H](NC(=O)Cc3ccccc3)C(=O)N2[C@H]1C(=O)OC(c1ccccc1)c1ccccc1
Agent: Cl
Agent: [Cl-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C=CCC(O)C1=CS[C@@H]2[C@H](NC(=O)Cc3ccccc3)C(=O)N2[C@H]1C(=O)OC(c1ccccc1)c1ccccc1
Reaction time: 0.33 h

Procedure:
Allylmagnesium chloride (2M in diethyl ether, 4.0 ml, 8 mmol) was added to a solution containing diphenylmethyl (4R, 6R, 7R)-3-formyl-7-phenylacetamidoceph-2-em-4-carboxylate (0.5 g, 1.0 mmol) and lithium chloride (0.35 g, 8 mmol) in tetrahydrofuran (5 ml) at −70° C. After 20 minutes at −70° C., hydrochloric acid (1M, 10 ml, 10 mmol) was added. Ethyl acetate was added and the organic layer was separated, washed with brine, dried (MgSO4), and evaporated. The resulting oil was purified by chromatography (20% to 60% ethyl acetate in hexane, silica gel) giving; first the title compound S-diastereomer, 90 mg (17%), dH (CDCl3) 2.18 (1H, dt, J 15 Hz and 8 Hz), 2.36 (1H, dt, J 17 and 5 Hz), 3.45 (2H, ABq), 4.18 (1H, m), 4.95-5.15 (4H, m), 5.55-5.7 (2H, m), 6.11 (1H, d, J 9 Hz), 6.36 (1H, s), 6.89 (1H, s), 7.3-7.4 (15H, m), and second; the title compound R-diastereomer, 250 mg (45%), dH (CDCl3) 2.28 (2H, t, J 7 Hz), 3.62 (2H, ABq), 4.15 (1H, t, J 7 Hz), 4.95-5.2 (4H, m), 5.5-5.65 (2H, m), 6.16 (1H, d, J 9 Hz), 6.20 (1H, s), 6.89 (1H, s), 7.3-7.4 (15H, m).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].Br[CH2:18][CH2:19][Cl:20]>CS(C)=O>[Cl:20][CH2:19][CH2:18][N:12]1[CH2:13][CH2:14][N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([Cl:2])[CH:4]=2)[CH2:10][CH2:11]1
Reactant: Clc1cccc(N2CCNCC2)c1
Reactant: ClCCBr
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Product: ClCCN1CCN(c2cccc(Cl)c2)CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 59.6 %

Procedure:
A mixture of (3-chloro-phenyl)-piperazine hydrochloride (51.5 mmol) and powdered sodium hydroxide (103 mmol) in DMSO (75 mL) was treated with 2-bromo-1-chloroethane (77.2 mmol) and stirred at ambient temperature for 4 h. The reaction was poured into ice cold water (200 mL) and stirred for 0.5 h. A solid mass formed and was separated by decanting the water. The aqueous layer was extracted with dichloromethane (100 mL). The solid mass was dissolved with dichloromethane (100 mL) and the combined organics were dried with sodium sulfate, filtered and the solvent removed under vacuum. Flash chromatography (chloroform:acetone 50:1 to 20:1) yielded an oil (7.95 g) as the titled compound.
Reaction SMILES: Br[C:2]1[S:6][C:5]2=[N:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=1>C(O)C(F)(F)F.ClCCl>[S:6]1[C:2]([NH:18][C:15]2[CH:16]=[CH:17][C:12]([O:11][CH3:10])=[CH:13][CH:14]=2)=[N:3][N:4]2[CH:9]=[CH:8][N:7]=[C:5]12
Reactant: Brc1nn2ccnc2s1
Reactant: COc1ccc(N)cc1
Solvent: ClCCl
Solvent: OCC(F)(F)F
Product: COc1ccc(Nc2nn3ccnc3s2)cc1
Temperature: 170 °C
Yield: 29.4 %

Procedure:
A mixture of 2-bromo-imidazo[2,1-b][1,3,4]thiadiazole (1.0 g, 4.90 mmol) and p-anisidine (19.6 mmol, 2.41 g) in trifluoroethanol (12 mL) was heated under microwave irradiation at 170° C. for 1 hour. On cooling, the mixture was diluted with dichloromethane (10 mL) and purified by column chromatography (Biotage™/Flash, silica, methanol: dichloromethane 0.2:9.8 to 1:9). The residue obtained was triturated with diethylether and few drops of methanol to give imidazo[2,1-b][1,3,4]thiadiazol-2-yl-(4-methoxyphenyl)amine as a white solid (355 mg, 29% yield).
Reaction SMILES: [CH2:1]([S:3][C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-])=O)=[CH:6][N:5]=1)[CH3:2].[Cl-].[NH4+].O>C(O)C>[NH2:10][C:7]1[CH:8]=[CH:9][C:4]([S:3][CH2:1][CH3:2])=[N:5][CH:6]=1
Reactant: CCSc1ccc([N+](=O)[O-])cn1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: CCSc1ccc(N)cn1
Yield: 88.4 %

Procedure:
A mixture of 5.0 g of 2-ethylthio-5-nitropyridine, 27 g of ammonium chloride, 54 ml of water, and 108 ml of ethanol is heated to 70°-80° C., and 16.2 g of reduced iron is added slowly with stirring. The mixture is stirred at the same temperature for 45 minutes. The hot reaction mixture is filtered, and the filtrate is concentrated. To the residue is added 50 ml of water, and the mixture is extracted with three 50-ml portions of chloroform. The combined extracts are washed with water, dried over magnesium sulfate and concentrated to give 3.7 g of crude 5-amino-2-ethylthiopyridine.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:11][O:12][C:13](=[O:30])[CH:14]([O:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[CH:25]1[O:29][CH2:28][CH2:27][O:26]1)[CH2:15][CH3:16].I[CH2:32][CH3:33]>C1COCC1.C(OCC)(=O)C>[CH3:11][O:12][C:13](=[O:30])[C:14]([O:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[CH:25]1[O:29][CH2:28][CH2:27][O:26]1)([CH2:32][CH3:33])[CH2:15][CH3:16]
Reactant: CCC(Oc1ccc(Cl)cc1C1OCCO1)C(=O)OC
Reactant: CCI
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCC(CC)(Oc1ccc(Cl)cc1C1OCCO1)C(=O)OC
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 97.3 %

Procedure:
Lithium bis(trimethylsilyl)amide (60 mL, 60 mmol, 1 M in THF) was slowly added to a solution of 2-(4-chloro-2-[1,3]dioxolan-2-yl-phenoxy)-butyric acid methyl ester (15 g, 50 mmol) in anhydrous THF (150 mL) at −78° C. After the mixture was stirred for 15 min, iodoethane (9.3 g, 60 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 2 h. Then the mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of NH4Cl, dried over anhydrous Na2SO4 and concentrated to give the crude product as a oil (16 g).
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.Cl[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[CH3:23]>>[CH3:23][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:17]=1[O:14][CH:11]1[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]1
Reactant: Cc1cnccc1Cl
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Agent: Cl
Product: Cc1cnccc1OC1CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 72 h

Procedure:
The title compound was prepared from 1-Boc-4-hydroxypiperidine and 4-chloro-3-methylpyridine hydrochloride, using a similar method to preparation 27. The reaction mixture was stirred for 72 hours to afford the title compound the desired product in 87% yield. 1H NMR(CDCl3, 400 MHz) δ: 1.44(s, 9H), 1.75-1.85(m, 2H), 1.87-1.97(m, 2H), 2.18(s, 3H), 3.42-3.53(m, 2H), 3.56-3.65(m, 2H), 4.57-4.65(m, 1H), 6.72(d, 1H), 8.29(s, 1H), 8.35(d, 1H); LRMS APCI m/z 293 [M+H]+
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[NH:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17]C(O)=O)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.C1C[O:34]CC1>>[C:1]([O:5][C:6](=[O:21])[NH:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][OH:34])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nn1ccc2cc(CC(=O)O)ccc21
Reactant: C1CCOC1
Agent: CC(C)C[AlH]CC(C)C
Product: CC(C)(C)OC(=O)Nn1ccc2cc(CO)ccc21
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 68 %

Procedure:
To a −78° C. solution of 5-(carboxymethyl)-indole-1-carbamic acid tert-butyl ester (10.8 g, 39 mmol) in THF (180 mL) was added DIBAL (127 mL of a 1 M solution in THF, 127 mmol), and the reaction mixture was stirred for 2.5 h. The reaction was quenched with 1:1 1 N HCl/MeOH (100 mL), the reaction mixture was warmed to room temperature, diluted with CH2Cl2 (100 mL), and separated. The organic solution was washed with saturated Rochelle salt, dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:1 EtOAc/hexanes) provided 5-hydroxymethylindole-1-carbamic acid tert-butyl ester as a yellow oil (6.5 g, 68%): 1H NMR (300 MHz, CDCl3) δ 8.07 (d, J=9 Hz, 1H), 7.59 (d, J=6 Hz, 1H), 7.54 (s, 1H), 7.28 (d, J=9 Hz, 1H), 6.58 (d, J=6 Hz, 1H), 4.73 (s, 2H), 1.97 (s, 9H).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.[Br:16][C:17]1[CH:18]=[C:19]([OH:24])[CH:20]=[C:21](Br)[CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:16][C:17]1[CH:18]=[C:19]([OH:24])[CH:20]=[C:21]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=2)[CH:22]=1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: Oc1cc(Br)cc(Br)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1cc(-c2cc(O)cc(Br)c2)cn1
Temperature: 800 °C
Yield: 37 %

Procedure:
1-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (750 mg; 3.6 mmol; 1.0 eq.), 3,5-Dibromo-phenol (4.54 g; 18.0 mmol; 5.0 eq.), bis(triphenylphosphine)palladium(II) chloride (253 mg; 0.36 mmol; 0.1 eq.) and potassium carbonate (2.49 g; 18.02 mmol; 5 eq.) were suspended in DMF (80 mL) and water (1 mL). The reaction mixture was then heated at 800° C. for 16 h in a sealed tube. It was filtered through Celite and the filtrate was concentrated under reduced pressure. Purification by flash chromatography on silica (n-heptane:EtOAc, gradient from 95:5 to 10:90) afforded the title compound as a clear oil (337 mg, 30%). 1H NMR (300 MHz, DMSO-d6) δ 10.01 (brs, 1H), 8.14 (s, 1H), 7.83 (d, J=0.7 Hz, 1H), 6.96 (d, J=1.7 Hz, 1H), 6.92 (dd, J=2.1, 1.5 Hz, 1H), 6.76 (t, J=2.0 Hz, 1H), 3.84 (s, 3H).
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[C:9]([C:14]2[N:19]=[N:18][C:17]([NH2:20])=[N:16][C:15]=2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:8]=1)(=O)=O.[CH2:29]([Sn](CCCC)(CCCC)C=C)[CH2:30]CC>>[Cl:13][C:11]1[CH:10]=[C:9]([C:14]2[N:19]=[N:18][C:17]([NH2:20])=[N:16][C:15]=2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:8]=[C:7]([CH:29]=[CH2:30])[CH:12]=1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: Nc1nnc(-c2cc(Cl)cc(OS(=O)(=O)C(F)(F)F)c2)c(-c2ccccc2)n1
Product: C=Cc1cc(Cl)cc(-c2nnc(N)nc2-c2ccccc2)c1
Yield: 11 %

Procedure:
6-(3-Chloro-5-ethenylphenyl)-5-phenyl-1,2,4-triazin-3-amine (54 mg, 11%) was prepared from 3-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-5-chlorophenyl trifluoromethanesulfonate (0.65 g, 1.51 mmol and tri-n-butyl(vinyl) tin (0.57 g, 1.81 mmol) according to the general procedure for Example 4.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[C:3](=[CH:4][C:5]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:6]([C:10](=[O:12])[CH3:11])[CH:7]=2)[O:2]1.[H-].[Na+].[CH3:23][O:24][C:25](=O)[O:26]C>>[CH2:1]1[O:9][C:8]2[C:3](=[CH:4][C:5]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:6]([C:10](=[O:12])[CH2:11][C:25]([O:24][CH3:23])=[O:26])[CH:7]=2)[O:2]1
Reactant: CC(=O)c1cc2c(cc1OCc1ccccc1)OCO2
Reactant: COC(=O)OC
Agent: [H-]
Agent: [Na+]
Product: COC(=O)CC(=O)c1cc2c(cc1OCc1ccccc1)OCO2
Yield: 91.2 %

Procedure:
A mixture of 1-[4,5-(methylenedioxy)-2-(phenylmethoxy)phenyl]ethanone (5.4 g, 0.02 mol), sodium hydride (1.6 g of 60% sodium hydride, 0.04 mol) and dimethylcarbonate (18 g, 0.2 mol) was heated to 70°-75° C. for 20 minutes. After evaporating the excess dimethylcarbonate under reduced pressure, the residue was acidified with 10% HCl solution and extracted with ether. The ether solution was washed with water, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was filtered through silica gel using chloroform as eluent to afford 5.99 g (91.3%) of methyl 4,5-(methylenedioxy)-β-oxo-2-(phenylmethoxy)benzenepropanoate mp (EtOH) 86°-86.5° C.; IR (KBr) 1750 (ester), 1652 (carbonyl) cm-1 ; NMR (CDCl3, 90 MHz) δ, 3.61 (S, 3H, CO2CH3), 3.92 (S, 2H, CH2CO2CH3), 5.11 (S, 2H, CH2Ph), 5.98 (S, 2H, OCH2O), 6.54 (S, 1H, ArH), 7.39 (S, 5H, CH2Ph), 7.41 (S, 1H, ArH). Anal. calcd. for C18H16O6 : C, 65.85; H, 4.91. Found: C, 65.92; H, 5.11.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[CH:7]=[C:8]([N+:13]([O-])=O)[C:9]=1[S:10][C:11]#[N:12])([O-:3])=[O:2].N>C(O)(=O)C.O.[Fe]>[N+:1]([C:4]1[C:9]2[S:10][C:11]([NH2:12])=[N:13][C:8]=2[CH:7]=[C:6]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[CH:5]=1)([O-:3])=[O:2]
Reactant: N#CSc1c([N+](=O)[O-])cc(-c2cccnc2)cc1[N+](=O)[O-]
Agent: [Fe]
Agent: N
Solvent: O
Solvent: CC(=O)O
Product: Nc1nc2cc(-c3cccnc3)cc([N+](=O)[O-])c2s1
Temperature: 25 °C
Reaction time: 16 h
Yield: 95.6 %

Procedure:
A solution of 3-(3,5-Dinitro-4-thiocyanato-phenyl)-pyridine (0.66 g, 2.19 mmol) in glacial acetic acid (15 ml) was treated with iron powder (0.61 g, 11.0 mmol) and stirred at ambient temperature for 16 h. The resultant mixture was diluted with water (200 ml) and made alkaline by the addition of concentrated ammonia solution. The solid material was collected by filtration and washed with water followed by ethyl acetate. The filtered solid was then extracted with boiling ethanol (3×200 ml) which was removed in vacuo to give 7-Nitro-5-pyridin-3-yl-benzothiazol-2-ylamine as a pale yellow solid (0.57 g, 95%).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:12][C:11]([CH3:14])([CH3:13])[CH2:10][CH:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:8]=2[CH:21]=1)(=[O:3])[CH3:2].ClC1C=CC=C(C(OO)=[O:30])C=1>ClCCl>[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:12][C:11]([CH3:14])([CH3:13])[CH2:10][CH:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N+:16]=3[O-:30])[C:8]=2[CH:21]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc2c(c1)C(c1ccccn1)CC(C)(C)O2
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CC(=O)c1ccc2c(c1)C(c1cccc[n+]1[O-])CC(C)(C)O2
Temperature: 25 °C
Reaction time: 72 h
Yield: 7.3 %

Procedure:
261 mg of 6-acetyl-3,4-dihydro-2,2 -dimethyl-4-(2-pyridyl)-2H-1-benzopyran were dissolved in 20 ml of dichloromethane at room temperature and 250 mg of m-chloroperbenzoic acid were added. After stirring at room temperature for 3 days the mixture was washed in succession with sodium bisulphite solution, sodium bicarbonate solution and water, dried over sodium sulphate and evaporated. The residue was chromatographed on silica gel using 2%-5% (v/v) methanol/chloroform for the elution. The resulting foam was triturated with methylcyclohexane and the solid obtained was recrystallized from t-butyl methyl ether to give 20 mg of 2-(6-acetyl-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)pyridine N-oxide of melting point 132°-133° C.