Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:29][O:28][CH:25]1[CH2:26][CH2:27][N:22]([CH2:21][C:18]2[CH:19]=[CH:20][C:15]([C:13]3[CH:12]=[N:11][C:6]4[NH:7][C:8]5[CH:9]=[N:10][C:2]([C:34]6[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=6)=[CH:3][C:4]=5[C:5]=4[CH:14]=3)=[CH:16][CH:17]=2)[CH2:23][CH2:24]1
Reactant: COC1CCN(Cc2ccc(-c3cnc4[nH]c5cnc(Br)cc5c4c3)cc2)CC1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: COC1CCN(Cc2ccc(-c3cnc4[nH]c5cnc(-c6cnn(C)c6)cc5c4c3)cc2)CC1
Temperature: 130 °C
Yield: 41.7 %

Procedure:
A degassed mixture of 6-bromo-3-[4-(4-methoxypiperidin-1-ylmethyl)-phenyl]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (0.16 g, 0.36 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.15 g, 0.72 mmol) and 1,1′-[bis(diphenyl phosphino)ferrocene]dichloropalladium(II) (29 mg, 0.036 mmol) in acetonitrile (3.6 mL) and saturated aqueous sodium carbonate solution (3.6 mL). The reaction mixture was heated under microwave irradiation at 130° C. for 20 minutes. The cooled reaction mixture was partitioned between DCM and water. The organic phase was dried over sodium sulfate, filtered and evaporated and the resultant residue was purified by flash chromatography (silica, 12 g column, ISCO, 0-15% methanol in DCM) to afford the title compound as a yellow solid (68 mg, 42%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.86 (d, J=1.1 Hz, 1H), 8.81 (d, J=2.2 Hz, 1H), 8.77 (d, J=2.2 Hz, 1H), 8.30 (d, J=1.1 Hz, 1H), 8.06-8.04 (m, 2H), 7.71 (d, J=7.9 Hz, 2H), 7.52 (d, J=2.0 Hz, 2H), 4.01 (s, 3H), 3.74-3.63 (m, 2H), 2.94-2.79 (m, 2H), 2.47-2.25 (m, 2H), 2.04-1.90 (m, 2H), 1.78-1.58 (m, 2H). LCMS (Method A): RT=4.76 min, M+H+=453.
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17](O)=[O:18])(=[O:11])=[O:10])=[CH:5][CH:4]=1.C([O-])(=O)C.[Na+]>C(OC(=O)C)(=O)C>[CH3:1][N:2]([CH3:20])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:13][CH2:14][CH2:15][CH2:16][C:17]2=[O:18])(=[O:11])=[O:10])=[CH:5][CH:4]=1
Reactant: CN(C)c1ccc(S(=O)(=O)NCCCCC(=O)O)cc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: CN(C)c1ccc(S(=O)(=O)N2CCCCC2=O)cc1
Temperature: 25 °C
Yield: 82 %

Procedure:
4.8 g of product obtained in stage A is heated to reflux for 3 hours with 4.8 g of sodium acetate in 48 cm3 of acetic anhydride. The mixture is cooled to room temperature and evaporated to dryness, the residue is taken up in 50 cm3 of water, filtered off and dried and 3.7 g of expected crude product are obtained. M.p. 165°-170° C. After crystallization in ethanol, 2.9 g of pure product are obtained. M.p. 169°-171° C.
Reaction SMILES: [CH:1]([C:4]1[C:5]2[CH:6]=[C:7]([CH3:28])[C:8]([NH:16][C:17]3[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=3)=[CH:9][C:10]=2[C:11]([CH3:15])([CH3:14])[CH2:12][CH:13]=1)([CH3:3])[CH3:2].[CH:29](=O)[CH3:30]>>[CH2:29]([N:16]([C:8]1[C:7]([CH3:28])=[CH:6][C:5]2[C:4]([CH:1]([CH3:3])[CH3:2])=[CH:13][CH2:12][C:11]([CH3:14])([CH3:15])[C:10]=2[CH:9]=1)[C:17]1[CH:18]=[CH:19][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:26][CH:27]=1)[CH3:30]
Reactant: CCOC(=O)c1ccc(Nc2cc3c(cc2C)C(C(C)C)=CCC3(C)C)cc1
Reactant: CC=O
Product: CCOC(=O)c1ccc(N(CC)c2cc3c(cc2C)C(C(C)C)=CCC3(C)C)cc1
Yield: 85.3 %

Procedure:
Following General Procedure D, ethyl 4-(5-isopropyl-3,8,8-trimethyl-7,8-dihydronaphthalen-2-ylamino)benzoate (Compound 48, 0.10 g, 0.26 mmol) was reacted with acetaldehyde (0.15 mL, 2.6 mmol) to give 0.090 g (90%) of the title compound as a clear oil.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:12][CH:11]=2)[C:5]([C:20]#[N:21])=[C:4](SC2C=CC=CC=2)[N:3]=1.CC(C)([O-])C.[K+].[N:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][OH:42])[CH:36]=1>>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:14][CH:15]=2)[C:5]([C:20]#[N:21])=[C:4]([O:42][CH2:41][C:37]2[CH:36]=[N:35][CH:40]=[CH:39][CH:38]=2)[N:3]=1
Reactant: OCc1cccnc1
Reactant: CC(=O)Nc1ccc(-c2c(C#N)c(N)nc(Sc3ccccc3)c2C#N)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: CC(=O)Nc1ccc(-c2c(C#N)c(N)nc(OCc3cccnc3)c2C#N)cc1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
115 mg (0.3 mmol) of N-{4-[2-amino-3,5-dicyano-6-(phenylsulfanyl)-4-pyridinyl]phenyl}acetamide [prepared analogously to Kambe et al., Synthesis, 531-533 (1981)] are, together with 50 mg (0.45 mmol) of potassium tert-butoxide, dissolved/suspended in 1.12 g (=1 ml, 10.3 mmol) of 3-pyridylmethyl alcohol, and the mixture is stirred at 60° C. for 2 h. The precipitate is filtered off with suction and suspended in a mixture of water and ethanol, and 0.3 ml of 5N acetic acid is added. After filtration, the product is purified by preparative HPLC on reversed-phase silica gel (gradient: water/acetonitrile 95:510:90 in 38 minutes).
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=2)[N:7]=1.[NH2:16][C:17]1[S:18][C:19]([C:25]2[C:30]([F:31])=[CH:29][C:28]([C:32]([OH:35])([CH3:34])[CH3:33])=[CH:27][C:26]=2[F:36])=[CH:20][C:21]=1[C:22]([NH2:24])=[O:23]>>[NH2:24][C:22]([C:21]1[CH:20]=[C:19]([C:25]2[C:30]([F:31])=[CH:29][C:28]([C:32]([OH:35])([CH3:34])[CH3:33])=[CH:27][C:26]=2[F:36])[S:18][C:17]=1[NH:16][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=2)[N:7]=1)=[O:23]
Reactant: CC(C)(O)c1cc(F)c(-c2cc(C(N)=O)c(N)s2)c(F)c1
Reactant: CCOC(=O)c1cn2nc(Cl)ccc2n1
Product: CCOC(=O)c1cn2nc(Nc3sc(-c4c(F)cc(C(C)(C)O)cc4F)cc3C(N)=O)ccc2n1

Procedure:
The title compound was prepared as described in Example 1, Step 5 using ethyl 6-chloroimidazo[1,2-b]pyridazine-2-carboxylate (430 mg, 1.92 mmol) and 2-amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (400 mg, 1.28 mmol) as starting materials.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([CH3:11])=[CH:4][C:3]=1[O:12][CH2:13][CH2:14][O:15][CH3:16].C([O:21]C(N(C)C)N(C)C)(C)(C)C>CN(C=O)C>[Cl:1][C:2]1[C:3]([O:12][CH2:13][CH2:14][O:15][CH3:16])=[CH:4][C:5]([CH:11]=[O:21])=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1
Reactant: COCCOc1cc(C)c([N+](=O)[O-])cc1Cl
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Solvent: CN(C)C=O
Product: COCCOc1cc(C=O)c([N+](=O)[O-])cc1Cl
Reaction time: 1 h

Procedure:
1-Chloro-2-(2-methoxyethoxy)-4-methyl-5-nitrobenzene (300 mg; 1.22 mmol) in DMF (3 ml) was treated with tert.butoxy-bis(dimethylamino)methan (1.06 ml; 5.1 mmol) in DMF (13 ml) at 160° C. for 20 min. The reaction mixture was evaporated to dryness and taken up in THF (6 ml). NalO4 (1.6 g; 7.3 mmol) in water (25 ml) was added at room temperature within 0.5 h and after stirring for another 1 h, the reaction mixture was extracted with EtOAc twice. The combined organic phases were dried over Na2SO4 and evaporated to dryness to yield the intermediate 4-chloro-5-(2-methoxyethoxy)-2-nitrobenzaldehyde as brown solid (360 mg; quant.). 4-chloro-5-(2-methoxyethoxy)-2-nitrobenzaldehyde (360 mg; 1.22 mmol) and (methoxycarbonylmethylen)triphenylphosphoran (449 mg; 1.34 mmol) were refluxed for 1 h in toluene (20 ml). After cooling the reaction mixture, toluene (100 ml) was added and the resulting crystals filtered off and purified via chromatography (SiO2, TBME/hexanes 1/1) to yield the title compound as a cis-trans mixture (290 mg). Recrystallisation from hot TBME rendered the pure trans isomer (180 mg; 47%) as slightly yellow crystals.
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[N:7][CH:8]=2)[N:3]1[CH2:12][C:13]([OH:15])=O.[S:16]1[CH:20]=[C:19]([C:21]2[S:22][CH:23]=[CH:24][C:25]=2[NH2:26])[N:18]=[CH:17]1>>[O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[N:7][CH:8]=2)[N:3]1[CH2:12][C:13]([NH:26][C:25]1[CH:24]=[CH:23][S:22][C:21]=1[C:19]1[N:18]=[CH:17][S:16][CH:20]=1)=[O:15]
Reactant: Nc1ccsc1-c1cscn1
Reactant: O=C(O)CN1C(=O)CCc2cnccc21
Product: O=C(CN1C(=O)CCc2cnccc21)Nc1ccsc1-c1cscn1

Procedure:
The title compound was prepared from 2-(2-oxo-3,4-dihydro-1,6-naphthyridin-1(2H)-yl)acetic acid (65 mg, 0.32 mmol) and 2-(thiazol-4-yl)thiophen-3-amine (57 mg, 0.32 mmol) according to protocol A. Retention time (min)=1.471, method [7], MS (ESI) 371.1 (M+H); 1H NMR (300 MHz, CDCl3) δ 11.48 (s, 1H), 8.87 (d, J=1.8 Hz, 1H), 8.48-8.76 (m, 1H), 7.99 (d, J=5.4 Hz, 1H), 7.37 (d, J=1.8 Hz, 1H), 7.27-2.28 (m, 2H), 7.23 (d, J=5.4 Hz, 1H), 4.91 (s, 2H), 3.20-3.25 (m, 2H), 2.96-3.01 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C:8](=O)[CH3:9])[CH:7]=1.C(O)=O.C([NH2:18])=O>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:8]([NH2:18])[CH3:9])[CH:7]=1
Reactant: NC=O
Reactant: COc1ccc(Cl)cc1C(C)=O
Solvent: O=CO
Solvent: O
Product: COc1ccc(Cl)cc1C(C)N
Temperature: 25 °C

Procedure:
1-(5-Chloro-2-methoxyphenyl)ethanone (6.7 g, 36.3 mmol) and formic acid (1.74 g, 27.7 mmol) were heated in formamide (10 mL) at 170° C. for 20 h. The mixture was cooled to room temperature, diluted with water and extracted with benzene. After removal of benzene by rotary evaporation the crude mixture was heated under reflux conditions in 3M HCl for 30 h. After cooling, the reaction was added to ether and extracted. The aqueous layer was basified with NaOH to pH 9 and extracted with dichloromethane. The dichloromethane was evaporated to collect the title compound (2.7 g, 40%). 1H NMR (400 MHz, CDCl3): δ 7.39 (d, 1H), 7.26 (q, 1H), 6.81 (d, 1H), 4.62 (m, 1H), 3.84 (s, 3H), 1.69 (d, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:22]=[CH:21][C:7]([O:8][C:9]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:23]1([CH2:29][CH2:30]Br)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH2:11][N:12]([CH2:30][CH2:29][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:13][CH2:14]2)=[CH:21][CH:22]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(OC2(c3ccccc3)CCNCC2)cc1
Reactant: BrCCc1ccccc1
Product: O=[N+]([O-])c1ccc(OC2(c3ccccc3)CCN(CCc3ccccc3)CC2)cc1

Procedure:
from 4-(4-nitrophenoxy)-4-phenylpiperidine and 2-phenylethyl bromide.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[Cl:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17](=[O:27])[C:18]([S:24]([CH3:26])=[O:25])=[CH:19][N:20]2[CH3:23])=[CH:15][CH:14]=1>C(Cl)(Cl)Cl>[Cl:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17](=[O:27])[C:18]([S:24]([CH3:26])(=[O:6])=[O:25])=[CH:19][N:20]2[CH3:23])=[CH:15][CH:14]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cn1cc(S(C)=O)c(=O)c2ccc(Cl)cc21
Solvent: ClC(Cl)Cl
Product: Cn1cc(S(C)(=O)=O)c(=O)c2ccc(Cl)cc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 3-chloroperoxybenzoic acid (85%, 6.75 g.) in chloroform (70 ml.) was added dropwise to a stirred solution of 7-chloro-1-methyl-3-methylsulphinyl-4-quinolone (6.25 g.) in chloroform (150 ml.). The resulting solution was stirred at room temperature for 2 hours and then washed repeatedly with saturated aqueous sodium carbonate solution to remove peroxide. The resulting solution was dried over anhydrous magnesium sulphate and then evaporated. The solid residue was crystallised from ethanol using charcoal to give 7-chloro-1-methyl-3-methylsulphonyl-4-quinolone, m.p. 241°-242°.
Reaction SMILES: C[O:2][C:3]([C:5]1[NH:6][CH:7]=[C:8]([C:10]2[CH:15]=[C:14]([C:16](=[O:24])[NH:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[CH:13]=[CH:12][C:11]=2[CH:25]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH3:26])[CH:9]=1)=[O:4].[Li+].[OH-]>C1COCC1.CO.C([O-])(O)=O.[Na+]>[C:31]([O:30][C:28]([NH:27][CH:25]([C:11]1[CH:12]=[CH:13][C:14]([C:16](=[O:24])[NH:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:15][C:10]=1[C:8]1[CH:9]=[C:5]([C:3]([OH:4])=[O:2])[NH:6][CH:7]=1)[CH3:26])=[O:29])([CH3:32])([CH3:33])[CH3:34]
Reactant: COC(=O)c1cc(-c2cc(C(=O)Nc3ccncc3)ccc2C(C)NC(=O)OC(C)(C)C)c[nH]1
Agent: O=C([O-])O
Agent: [Li+]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CC(NC(=O)OC(C)(C)C)c1ccc(C(=O)Nc2ccncc2)cc1-c1c[nH]c(C(=O)O)c1
Temperature: 40 °C
Reaction time: 1.5 h

Procedure:
To a solution of 4-[2-(1-tert-Butoxycarbonylamino-ethyl)-5-(pyridin-4-ylcarbamoyl)-phenyl]-1H-pyrrole-2-carboxylic acid methyl ester (661 μmol) in THF (1.6 ml) and MeOH (1.6 ml) was added a 1N LiOH solution (1.6 ml). The reaction mixture was stirred at 40° C. for 1.5 hours. The reaction mixture was diluted with saturated NaHCO3 and extracted with EtOAc. The aqueous layer is acidified with a 20% citric acid solution and extracted again with EtOAc. The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH:6]=[CH:7][N+:8]([O-:10])=[O:9].[CH2:16]([N:18]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:19](=[S:21])[S-:20])[CH3:17].[NH4+]>>[CH2:16]([N:18]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:19](=[S:20])[S:21][CH:6]([CH2:7][N+:8]([O-:10])=[O:9])[C:5]1[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:17]
Reactant: CCN(C(=S)[S-])c1ccccc1
Reactant: COc1ccc(C=C[N+](=O)[O-])cc1OC
Agent: [NH4+]
Product: CCN(C(=S)SC(C[N+](=O)[O-])c1ccc(OC)c(OC)c1)c1ccccc1

Procedure:
Reaction of 3,4-dimethoxy-β-nitrostyrene with ammonium ethyldithiocarbanilate by the above procedure yields 3,4-dimethoxy-α-(nitromethyl)benzyl ethyldithiocarbanilate.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@:9]1([C:20]([O:22][CH3:23])=[O:21])[CH2:18][CH2:17][C:16]2[C:11](=[C:12]([OH:19])[CH:13]=[CH:14][CH:15]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[C:27]1[CH:38]=[CH:37][CH:36]=[CH:35][C:28]=1[C:29]([O:31][CH2:32][CH:33]=[CH2:34])=[O:30].C(OCC)(=O)C.CCCCCC>N1C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@@:9]1([C:20]([O:22][CH3:23])=[O:21])[CH2:18][CH2:17][C:16]2[C:11](=[C:12]([O:19][C:27]3[CH:38]=[CH:37][CH:36]=[CH:35][C:28]=3[C:29]([O:31][CH2:32][CH:33]=[CH2:34])=[O:30])[CH:13]=[CH:14][CH:15]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CCOC(=O)c1ccccc1I
Reactant: COC(=O)[C@]1(NC(=O)OC(C)(C)C)CCc2cccc(O)c2C1
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: C=CCOC(=O)c1ccccc1Oc1cccc2c1C[C@](NC(=O)OC(C)(C)C)(C(=O)OC)CC2
Yield: 79.5 %

Procedure:
In analogy to Example 4.1.a, 2.5 g (7.78 mmol) of methyl (S)-2-(tert.butoxycarbonylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate in 5 ml of pyridine were reacted at 130° for 2 hours with 370 mg of sodium hydride dispersion, 2.23 g (10.9 mmol) of copper bromide-dimethyl sulphide complex and 4.48 g (15.56 mmol) of prop-2-enyl 2-iodobenzoate. After chromatography on 500 g of silica gel with ethyl acetate/hexane (1:9→1:1) there were obtained 2.98 g (80%) of methyl (S)-2-(tert.butoxycarbonylamino)-8-[2-(prop-2-enyloxycarbonyl)phenoxy]-1,2,3,4-tetrahydronaphthalene-2-carboxylate as a viscous oil. [α]D ==57.0° (c=0.4, chloroform
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([B:6]2[O:14][C:11]([CH3:13])([CH3:12])[C:8]([CH3:10])([CH3:9])[O:7]2)[CH:3]=[N:2]1.Cl[CH2:16][C:17]([N:19]([CH3:21])[CH3:20])=[O:18]>>[CH3:20][N:19]([CH3:21])[C:17](=[O:18])[CH2:16][N:2]1[CH:3]=[C:4]([B:6]2[O:7][C:8]([CH3:9])([CH3:10])[C:11]([CH3:13])([CH3:12])[O:14]2)[CH:5]=[N:1]1
Reactant: CN(C)C(=O)CCl
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Product: CN(C)C(=O)Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1

Procedure:
The title compound was prepared from pyrazole-4-boronic acid pinacol ester and 2-chloro-N,N-dimethylacetamide according to Method AC (heating to 90° C. for 4 h) and was isolated as an orange gum (quantitative). LCMS (ES+) 280 (M+H)+, RT 2.38 minutes (Method 1).
Reaction SMILES: [O:1]1[C:7]2[CH:8]=[CH:9][C:10]([CH2:12][N:13]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:14]([C@@H:16]3[O:21][CH2:20][CH2:19][NH:18][CH2:17]3)=[O:15])=[CH:11][C:6]=2[O:5][CH2:4][CH2:3][CH2:2]1.[CH3:26][O:27][C:28]1[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=1[CH:30]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CO.C1COCC1>[O:1]1[C:7]2[CH:8]=[CH:9][C:10]([CH2:12][N:13]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:14]([C@@H:16]3[O:21][CH2:20][CH2:19][N:18]([CH2:30][C:29]4[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=4[O:27][CH3:26])[CH2:17]3)=[O:15])=[CH:11][C:6]=2[O:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)CN(Cc1ccc2c(c1)OCCCO2)C(=O)[C@H]1CNCCO1
Reactant: COc1ccccc1C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccccc1CN1CCO[C@@H](C(=O)N(Cc2ccc3c(c2)OCCCO3)CC(C)C)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 0.1 g of (−)-(2R)—N-(3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-N-isobutylmorpholine-2-carboxamide, 0.05 g of 2-methoxybenzaldehyde, 0.1 g of sodium triacetoxyborohydride, 0.1 mL of acetic acid and 5 mL of THF was stirred overnight room temperature, then concentrated under reduced pressure. The residue was partitioned between 3×10 mL of ethyl acetate and 10 mL of saturated sodium carbonate, dried over magnesium sulfate and concentrated under reduced pressure. Preparative TLC eluting with 25% ethyl acetate in hexanes gave the product as a resin: [α]D23° C.=5.7° (c=1.0, MeOH); MS (m+1)=469.3; 1H NMR (500 MHz, CDCl3) 7.34-7.21 (m, 2H), 6.93-6.85 (m, 3H), 6.81-6.71 (m, 2H), 4.64 (m, 1H), 4.41-4.17 (m, 6H), 3.3 (m, 1H), 3.81 (d, 3H), 3.73-3.60 (m, 3H), 3.33-3.16 (m, 1H), 3.01-2.88 (m, 2H), 2.71 (m, 1H), 2.53 (t, 1H) 2.39-2.28 (m, 1H), 2.18 (m, 2H), 1.97 (m, 1H), 0.87 (m, 6H).
Reaction SMILES: Br[C:2]1[CH:20]=[CH:19][C:5]([C:6]([C:8]2[CH:9]=[CH:10][C:11]([Cl:18])=[C:12]([S:14]([NH2:17])(=[O:16])=[O:15])[CH:13]=2)=[O:7])=[CH:4][CH:3]=1.[N+:21]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)([O-:23])=[O:22]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:18][C:11]1[CH:10]=[CH:9][C:8]([C:6]([C:5]2[CH:19]=[CH:20][C:2]([C:28]3[CH:27]=[CH:26][CH:25]=[C:24]([N+:21]([O-:23])=[O:22])[CH:29]=3)=[CH:3][CH:4]=2)=[O:7])=[CH:13][C:12]=1[S:14]([NH2:17])(=[O:16])=[O:15]
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Reactant: NS(=O)(=O)c1cc(C(=O)c2ccc(Br)cc2)ccc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Solvent: O
Product: NS(=O)(=O)c1cc(C(=O)c2ccc(-c3cccc([N+](=O)[O-])c3)cc2)ccc1Cl
Yield: 20.4 %

Procedure:
A mixture of 220 mg of 5-(4-bromo-benzoyl)-2-chloro-benzenesulfonamide (0.587 mmol, 1 equivalent), 196 mg of 3-nitrobenzene boronic acid (1.174 mmol, 2 equivalent), 556 mg of Ba(OH)2 (1.761 mmol, 3 equivalent), and 14 mg of Pd(PPh3)4 in degassed dioxane/water (30 mL/10 mL) is refluxed for 18 h. The reaction is quenched with 1 N HCl and extracted with ethyl acetate. The combined organic extracts are dried over sodium sulfate, and concentrated in vacuo. After purification by flash chromatography, 50 mg of the title compound is obtained as white solid. 1H NMR (400 MHz, CDCl3): δ 5.2 (br, 2H), 6.18 (br, 1H), 7.02 (d, 2H, J=8 Hz), 7.12-7.45 (m, 5H), 7.6-7.8 (m, 3H), 7.90 (dd, 1H), 8.41 (s, 1H). MS (m/z): 387 (M+1).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([O:25][CH3:26])[CH:17]=[C:18]3[C:23]=2[N:22]=[C:21](C)[CH:20]=[CH:19]3)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N[C:28]1C=C(OC)C=C2C=1N=CC(C)=C2.NC1C=C(OC)C=C2C=1N=C(C)C=C2>>[CH2:1]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:15]=[C:16]([O:25][CH3:26])[CH:17]=[C:18]3[C:23]=2[N:22]=[CH:21][C:20]([CH3:28])=[CH:19]3)[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1cc(N)c2ncc(C)cc2c1
Reactant: COc1cc(N2CCN(Cc3ccccc3)CC2)c2nc(C)ccc2c1
Agent: COc1cc(N)c2nc(C)ccc2c1
Product: COc1cc(N2CCN(Cc3ccccc3)CC2)c2ncc(C)cc2c1
Yield: 22 %

Procedure:
The title compound was prepared by the same method used for 1-benzyl-4-(6-methoxy-2-methylquinolin-8-yl)piperazine, except substituting 8-amino-6-methoxy-3-methylquinoline (2.82 g, 15.0 mmol) for the 8-amino-6-methoxy-2-methyl-quinoline. Flash chromatography on 6×20 cm SiO2 (25-30% EtOAc/hexane), with rechromatography of the mixed fractions, provided 1.13 g (22%) of the title compound as a yellow gum. Crystallization from hexane afforded 0.88 g of analytically pure compound as yellow crystals: mp 112-113° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[CH:8]=[CH:9][NH:10][C:6]=2[CH:5]=[C:4]([Cl:11])[N:3]=1.[H-].[Na+].I[CH3:15]>O1CCCC1>[Cl:1][C:2]1[C:7]2[CH:8]=[CH:9][N:10]([CH3:15])[C:6]=2[CH:5]=[C:4]([Cl:11])[N:3]=1
Reactant: Clc1cc2[nH]ccc2c(Cl)n1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cn1ccc2c(Cl)nc(Cl)cc21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 96 %

Procedure:
A solution of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine (270 mg, 1.44 mmol) in tetrahydrofuran (4 mL) at 0° C. was treated with a 60% dispersion of sodium hydride in mineral oil (69.3 mg, 2.89 mmol) followed by iodomethane (225 mg, 1.59 mmol). After stirring at 0° C. for 0.5 h, the reaction mixture was allowed to warm to room temperature and was stirred at room temperature for 5 h. At this time, the resulting mixture was quenched with a saturated aqueous sodium bicarbonate solution. The reaction mixture was extracted with ethyl acetate. The combined organics were washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (30% ethyl acetate/hexanes) afforded 4,6-dichloro-1-methyl-1H-pyrrolo[3,2-c]pyridine (278 mg, 95.8%). LC-MS calcd. for C8H6Cl2N2 [(M+H)+] 201, obsd. 200.8.
Reaction SMILES: C[O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:13]3[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=3)[CH:9]=2)[C:4]=1[F:21].B(Br)(Br)Br>>[F:21][C:4]1[C:5]2[C:10](=[CH:9][C:8]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)=[CH:7][CH:6]=2)[CH:11]=[CH:12][C:3]=1[OH:2]
Reactant: COc1ccc(-c2ccc3c(F)c(OC)ccc3c2)cc1
Agent: BrB(Br)Br
Product: Oc1ccc(-c2ccc3c(F)c(O)ccc3c2)cc1

Procedure:
The title compound was prepared by reacting 2-methoxy-6-(4-methoxyphenyl)-1-fluoronaphthalene (0.250 g, 0.886 mmol) with boron tribromide (2.7 mL of 1 N solution, 2.7 mmol) according to method D to yield 0.13 g (15%) of a white solid: mp 219–224° C.; 1H NMR (DMSO-d6): δ (6.89 (2H, d, J=8.49 Hz), 7.22–7.28 (1H, m), 7.61 (2H, d, J=8.53 Hz), 7.65 (1H, d, J=9.12 Hz), 7.79 (1H, d, J=8.77 Hz), 7.92 (1H, d, J=8.73 Hz), 8.05 (1H, s), 9.63 (1H, bs), 10.00 (1H, bs); MS (ESI) m/z 253 (M−H)−.
Reaction SMILES: [CH3:1][C:2]1[C:10]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(OCC)C.O.[Cl-].[Na+]>O1CCCC1>[CH3:1][C:2]1[C:10]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:9][CH:8]=[CH:7][C:3]=1[CH2:4][OH:5]
Reactant: Cc1c(C(=O)O)cccc1-c1cccs1
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: Cc1c(CO)cccc1-c1cccs1
Temperature: 25 °C
Reaction time: 0.58 h
Yield: 99.8 %

Procedure:
Under an argon atmosphere, a stirred solution of 5.7 g (0.026 mol) of 2-methyl-3-(2-thienyl)benzoic acid in 50 mL of tetrahydrofuran was cooled to 0° C.±2° C. To this solution was added dropwise 4.4 g (0.051 mol, 51.3 mL of a 1.0 M solution) of borane tetrahydrofuran complex. The addition was made over 35 minutes. The reaction mixture was stirred for 0.5 hour at ambient temperature, then for two hours at reflux temperature. The reaction mixture was cooled, and 100 mL of diethyl ether saturated with water, then 20 mL of water, were cautiously added. The mixture was transferred to a separatory funnel containing 50 mL of ice, and was saturated with solid sodium chloride, and extracted with three portions of 200 mL each of diethyl ether. The combined extracts were dried with magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to give 5.3 g of 2-methyl-3-(2-thienyl)phenylmethanol as an oil.