Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.Br[C:11]1[CH:15]=[CH:14][S:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].O>CN1CCCC1=O.[Cu](Br)Br>[S:13]1[CH:14]=[CH:15][C:11]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)=[CH:12]1
Reactant: c1ccc2[nH]ccc2c1
Reactant: Brc1ccsc1
Agent: Br[Cu]Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN1CCCC1=O
Product: c1ccc2c(c1)ccn2-c1ccsc1
Temperature: 180 °C

Procedure:
A mixture of indole (16 g, 0.136 M), 3-bromothiophene (24.75 g, 0.146 M), potassium carbonate (20.1 g, 0.146 M) and copper bromide (0.84 g, 0.003 M) in 160 ml of N-methyl-2-pyrrolidinone was stirred and heated to 180° C. (under nitrogen atmosphere) for 42 hours. After this time, the reaction mixture was poured onto 800 ml of water and extracted with ethyl acetate (2×350 ml). The combined ethyl acetate extracts were washed with water, brine, dried over magnesium sulfate, filtered and concentrated in vacuo leaving a dark brownblack oil. The crude reaction product was chromatographed on a silica gel column with hexane/CH2Cl2 3:1 as eluant. Yield=9.14 g of yellow liquid which was homogeneous by thin layer chromatography. MS: M+ =199.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([C:15]2[NH:16][C:17](=[O:32])[C:18]3[C:19](=[C:21]([CH2:30][CH3:31])[N:22]([CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[N:23]=3)[N:20]=2)[C:7]([O:10][CH2:11][CH2:12][CH2:13][CH3:14])=[N:8][CH:9]=1)(=[O:3])[CH3:2].C=O.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[C:1]([C:4]1[CH:5]=[C:6]([C:15]2[NH:16][C:17](=[O:32])[C:18]3[C:19](=[C:21]([CH2:30][CH3:31])[N:22]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:35])[CH2:26][CH2:25]4)[N:23]=3)[N:20]=2)[C:7]([O:10][CH2:11][CH2:12][CH2:13][CH3:14])=[N:8][CH:9]=1)(=[O:3])[CH3:2]
Reactant: CCCCOc1ncc(C(C)=O)cc1-c1nc2c(CC)n(C3CCNCC3)nc2c(=O)[nH]1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C=O
Agent: [Na+]
Solvent: ClCCl
Product: CCCCOc1ncc(C(C)=O)cc1-c1nc2c(CC)n(C3CCN(C)CC3)nc2c(=O)[nH]1
Reaction time: 14 h
Yield: 39.4 %

Procedure:
5-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-(4-piperidinyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (Example 49) (100 mg, 0.23 mmol) was dissolved in dichloromethane (10 mL) and formaldehyde (27 mg, 0.01 mL of a 37-41% solution) was added. After 30 min stirring sodium triacetoxyborohydride (108 mg, 0.51 mmol) was added and stirring continued for 14 h. Further formaldehyde (0.01 mL of 37-41% solution) and sodium triacetoxyborohydride (108 mg, 0.51 mmol) were added and stirring continued for a further 4.5 h. Starting material still remained so further formaldehyde (0.01 mL of 37-41% solution) and sodium triacetoxyborohydride (108 mg, 0.51 mmol) were added and stirring continued for a further 18 h. The reaction mixture was diluted with dichloromethane, washed with sodium bicarbonate solution then brine, dried (MgSO4) and concentrated. Purification by flash column chromatography (elution with 94:6:0.6 dichloromethane/methanol/0.88 ammonia) gave the product (41 mg) as a white solid.
Reaction SMILES: F[C:2]1[CH:19]=[CH:18][C:5]([C:6]([C:8]2[C:9]([C:14]([O:16][CH3:17])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=2)=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].[NH:22]1[CH:26]=[CH:25][N:24]=[CH:23]1>CN(C=O)C>[N:22]1([C:2]2[CH:19]=[CH:18][C:5]([C:6]([C:8]3[C:9]([C:14]([O:16][CH3:17])=[O:15])=[N:10][CH:11]=[CH:12][CH:13]=3)=[O:7])=[CH:4][CH:3]=2)[CH:26]=[CH:25][N:24]=[CH:23]1
Reactant: c1c[nH]cn1
Reactant: COC(=O)c1ncccc1C(=O)c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ncccc1C(=O)c1ccc(-n2ccnc2)cc1
Temperature: 120 °C

Procedure:
A solution of 3-(4-fluorobenzoyl)-2-carbomethoxypyridine (2.37 g, 9.14 mmol) in 30 mL of DMF is added dropwise to a solution of NaH (0.43 g, 10.75 mmol) and imidazole (0.62 g, 9.14 mmol) in 26 mL of DMF. The mixture is heated at 120° C. for 1 day, then allowed to cool, quenched with ice H2O, and extracted with EtOAc (3×50 mL). The combined organic layers are dried (Na2SO4), evaporated, and the residue chromatographed on silica gel (eluting with EtOAc-CH3OH, 9:1) to generate 3-[4-(1H-imidazol-1-yl)benzoyl]-2-carbomethoxypyridine. M.P. 150°-157° C.
Reaction SMILES: Cl.C([C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)#N.[OH-].[K+].C1(C)C=CC=CC=1>O>[C:10]1([CH:4]2[CH2:5][CH2:6][NH:7][CH2:8][CH2:9]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: N#CC1(c2ccccc2)CCNCC1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Product: c1ccc(C2CCNCC2)cc1
Temperature: 160 °C
Reaction time: 4 h

Procedure:
4-Cyano-4-phenylpiperidine hydrochloride (10.0 g, 45.0 mmol) was combined with KOH pellets and stirred vigorously under Ar at 160° C. for 4 h. The reaction mix was cooled to RT and dissolved into toluene (100 ml) and H2O (100 ml). After separation of the layers, the aqueous layer was back-extracted two times with toluene. The combined organic layer was dried over Na2SO4, concentrated in vacuo, and dried under high vacuum, yielding a white solid.
Reaction SMILES: [C:1]1([C:7]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[CH2:18][CH2:17]3)=[CH:8][N:9]2[CH:13]=[CH:12][N:11]=[CH:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C(O)C.[Pd]>[C:1]1([CH:7]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[CH2:18][CH2:17]3)[CH2:8][N:9]2[CH:13]=[CH:12][N:11]=[CH:10]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: [H][H]
Reactant: O=C1CCc2cc(C(=Cn3ccnc3)c3ccccc3)ccc2N1
Agent: [Pd]
Solvent: CCO
Product: O=C1CCc2cc(C(Cn3ccnc3)c3ccccc3)ccc2N1

Procedure:
A solution of 390 mg of a mixture of (E) and (Z) isomers of 6-[1-phenyl-2-(imidazol-1-yl)ethenyl]-3,4-dihydrocarbostyril in 10 ml of ethanol was stirred under hydrogen in the presence of 200 mg of a 10% palladium on charcoal catalyst until the theoretical amount of hydrogen had been absorbed. The catalyst was filtered off, the solvent removed from the filtrate under reduced pressure and the residue chromatographed on silica gel eluting with 5% methanol in methylene chloride, yielding 6-[1-phenyl-2-(imidazol-1-yl)ethyl]-3,4-dihydrocarbostyril, having a melting point of 87°-94° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=O)[C:5]2=O.[NH2:13][C:14]1[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:15]=1[NH:16]C.Br.O>C(O)(=O)C>[CH3:22][C:20]1[CH:21]=[C:14]2[C:15](=[CH:18][CH:19]=1)[N:16]=[C:6]1[NH:7][C:8]3[CH:9]=[CH:10][C:2]([Br:1])=[CH:3][C:4]=3[C:5]1=[N:13]2
Reactant: CNc1ccc(C)cc1N
Reactant: O=C1Nc2ccc(Br)cc2C1=O
Agent: Br
Solvent: CC(=O)O
Solvent: O
Product: Cc1ccc2nc3[nH]c4ccc(Br)cc4c3nc2c1
Reaction time: 2 h

Procedure:
A solution of 2.26 g 5-bromoisatin (0.01 mole) and 1.36 g 2-amino N-methyl-p-toluidine (0.01 mole) in 15 ml acetic acid is boiled with reflux for 45 minutes. Finally hydrogen bromide is introduced and the mixture is boiled for further 2 hours. After cooling it is poured into water. The dried reaction product is recrystallized from acetic acid.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.Cl.[NH2:18][CH2:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.[NH4+].[OH-].CO>C(Cl)Cl>[NH2:18][CH2:19][C:20]1[CH:25]=[C:24]([C:2]2[N:3]=[C:4]3[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: NCc1cccc(B(O)O)c1
Reactant: CC(C)(C)C(=O)c1c[nH]c2ncc(Br)nc12
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)C(=O)c1c[nH]c2ncc(-c3cccc(CN)c3)nc12

Procedure:
1-[2-(3-Aminomethyl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one was prepared starting from 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one and (3-aminomethylphenyl)boronic acid hydrochloride following general procedures as described in these Examples. Silica gel chromatography using 0-20% [5% NH4OH:MeOH]/DCM as eluant gave a brown solid which was washed with 1:2 Et2O/Hexanes to provide 75 mg (48%) of a pale brown solid. MP 176-178° C., M+H=309.
Reaction SMILES: C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]#[N:19])[CH2:7][CH2:6]1)=O.O.[NH2:21][NH2:22]>C(O)CCC>[C:18]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[O:11][C@H:8]1[CH2:9][CH2:10][C@H:5]([C:3]([NH:21][NH2:22])=[O:2])[CH2:6][CH2:7]1)#[N:19]
Reactant: COC(=O)[C@H]1CC[C@H](Oc2ccccc2C#N)CC1
Reactant: NN
Solvent: O
Solvent: CCCCO
Product: N#Cc1ccccc1O[C@H]1CC[C@H](C(=O)NN)CC1
Temperature: 120 °C

Procedure:
A mixture of trans-4-(2-cyano-phenoxy)-cyclohexanecarboxylic acid methyl ester (0.20 g, 0.77 mmol) and hydrazine hydrate (0.037 ml, 0.76 mmol) in n-butanol (0.5 ml) was heated at 120° C. for 22 h. After cooling to room temperature the reaction mixture was partitioned between ethyl acetate (50 ml) and 1 M aqueous sodium hydroxide solution (50 ml). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated in vacuo to give the crude title compound (0.18 g, 90%) as white solid, which was used in the next step without further purification. MS m/e: 260 (M+H+)
Reaction SMILES: C(O[C:4](=[O:13])[CH2:5][NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C.[Cl:14][C:15]1[C:16]([CH3:24])=[C:17]([N:21]=[C:22]=[S:23])[CH:18]=[CH:19][CH:20]=1>C(Cl)(Cl)Cl>[Cl:14][C:15]1[C:16]([CH3:24])=[C:17]([N:21]2[C:4](=[O:13])[CH2:5][N:6]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:22]2=[S:23])[CH:18]=[CH:19][CH:20]=1
Reactant: Cc1c(Cl)cccc1N=C=S
Reactant: CCOC(=O)CNc1ccccc1
Solvent: ClC(Cl)Cl
Product: Cc1c(Cl)cccc1N1C(=O)CN(c2ccccc2)C1=S
Yield: 33.5 %

Procedure:
A mixture of N-phenyl glycine ethyl ester (8.95 g), 3-chloro-2-methylphenylisothiocyanate (9.18 g), and chloroform (200 mL) was heated at reflux for 18 hours. The solvent was evaporated to dryness. The residue was mixed with ethanol (150 mL), and triethyl amine (3 mL). The mixture was heated at reflux for 3 hours. The solvent was evaporated. The residue was dissolved in ethyl acetate (300 mL) and washed with 1N HCl (2×200 mL), then with water (200 mL). The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was treated with diethyl ether. The solid was collected by filtration and air dried to give the title compound (5.3 g) as an off-white solid, m.p. 154°-156° C. Anal. Calcd. for. C16H13Cl N2O S: C, 60.66; H, 4.14; N, 8.84. Found: C, 60.48; H, 4.05; N, 8.76. Mass spectrum (+FAB, [M+H]+) m/z 317/319.
Reaction SMILES: ClC1C=C(Cl)C=CC=1C1C(C2NC=CN=2)=CN=C(CCN)N=1.Cl[C:24]1[N:29]=[C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:27]([N+:35]([O-:37])=[O:36])=[CH:26][CH:25]=1.[Cl:38][C:39]1[CH:44]=[C:43]([Cl:45])[CH:42]=[CH:41][C:40]=1[C:46]1[C:51]([C:52]2[NH:53][CH:54]=[CH:55][N:56]=2)=[CH:50][N:49]=[C:48]([NH:57][CH2:58][CH2:59][NH:60]C2C=CC([N+]([O-])=O)=C(OC)N=2)[N:47]=1>>[Cl:38][C:39]1[CH:44]=[C:43]([Cl:45])[CH:42]=[CH:41][C:40]=1[C:46]1[C:51]([C:52]2[NH:56][CH:55]=[CH:54][N:53]=2)=[CH:50][N:49]=[C:48]([NH:57][CH2:58][CH2:59][NH:60][C:24]2[N:29]=[C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:27]([N+:35]([O-:37])=[O:36])=[CH:26][CH:25]=2)[N:47]=1
Reactant: COc1nc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]
Reactant: CS(=O)(=O)Nc1nc(Cl)ccc1[N+](=O)[O-]
Agent: NCCc1ncc(-c2ncc[nH]2)c(-c2ccc(Cl)cc2Cl)n1
Product: CS(=O)(=O)Nc1nc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]

Procedure:
{6-[(2-{[4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]amino}-ethyl)amino]-3-nitro(2-pyridyl)}(methylsulfonyl)amine was prepared from [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-ylethylamine and (6-chloro-3-nitro(2-pyridyl))(methylsulfonyl)amine in accordance with the procedure described above for the preparation of [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(6-methoxy-5-nitro(2-pyridyl))amino]ethyl}amine.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=O.[H][H]>>[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=C(CCCBr)c1ccccc1
Reactant: [H][H]
Product: BrCCCCc1ccccc1

Procedure:
Subsequently, the 4-bromobutyrophenone (3) as obtained above is reacted with hydrogen in the presence of a metal catalyst to give 1-bromo-4-phenylbutane.
Reaction SMILES: [C:1]([N:5]([CH2:11][CH3:12])[C:6](=[O:10])[O:7][CH2:8]Cl)([CH3:4])([CH3:3])[CH3:2].[OH:13][C@@H:14]([C@H:16]1[C:36](=[O:37])[N:18]2[C:19]([C:33]([O-:35])=[O:34])=[C:20]([S:23]/[CH:24]=[CH:25]\[C:26]3[S:30][CH:29]=[N:28][C:27]=3[CH2:31][OH:32])[C@H:21]([CH3:22])[C@H:17]12)[CH3:15].[Na+]>>[OH:13][C@@H:14]([C@H:16]1[C:36](=[O:37])[N:18]2[C:19]([C:33]([O:35][CH2:8][O:7][C:6]([N:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:11][CH3:12])=[O:10])=[O:34])=[C:20]([S:23]/[CH:24]=[CH:25]\[C:26]3[S:30][CH:29]=[N:28][C:27]=3[CH2:31][OH:32])[C@H:21]([CH3:22])[C@H:17]12)[CH3:15]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(S/C=C\c3scnc3CO)[C@H](C)[C@H]12
Reactant: CCN(C(=O)OCCl)C(C)(C)C
Agent: [Na+]
Product: CCN(C(=O)OCOC(=O)C1=C(S/C=C\c2scnc2CO)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12)C(C)(C)C
Yield: 68.2 %

Procedure:
In the same manner as in step b) in Example 125, 273 mg of the title compound was prepared from 180 mg of chloromethyl N-t-butyl-N-ethylcarbamate and 300 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate.
Reaction SMILES: N1CCCCC1.[CH:7]1([O:12][C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=2[O:21][CH3:22])[CH:16]=O)[CH2:11][CH2:10][CH2:9][CH2:8]1.C([CH2:26][C:27]([NH:29][C:30]1[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=1[C:32]([OH:34])=[O:33])=[O:28])(O)=O.Cl>C1(C)C=CC=CC=1>[CH:7]1([O:12][C:13]2[CH:14]=[C:15](/[CH:16]=[CH:26]/[C:27]([NH:29][C:30]3[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=3[C:32]([OH:34])=[O:33])=[O:28])[CH:18]=[CH:19][C:20]=2[O:21][CH3:22])[CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: O=C(O)CC(=O)Nc1ccccc1C(=O)O
Reactant: COc1ccc(C=O)cc1OC1CCCC1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: C1CCNCC1
Product: COc1ccc(/C=C/C(=O)Nc2ccccc2C(=O)O)cc1OC1CCCC1
Yield: 63.3 %

Procedure:
Piperidine (0.63 mL, 5.8 mmol) was added to a suspension of 3-cyclopentyloxy-4-methoxybenzaldehyde (1.4 g, 6.4 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (1.3 g, 5.8 mmol) in toluene (5.0 mL) and treated according to Procedure 2, acidifying with 1 M HCl. The crude product was recrystallised from EtOH/water providing (E)-2-{[3-(3-cyclopentyloxy-4-methoxyphenyl)-1-oxo-2-propenyl]amino}benzoic acid (1.4 g, 67%) as a yellow crystalline solid; mp 211-217° C.; δH (400 MHz, DMSO-d6) 1.57 (m, 2H, CH2), 1.70-1.72 (m, 4H, CH2), 1.91 (m, 2H, CH2), 3.78 (s, 3H, OCH3), 4.90 (t, J=5.6 Hz, 1H, OCH), 6.75 (d, J=15.6 Hz, 1H, CH═CHCO), 6.98 (d, J5′,6′=8.4 Hz, 1H, H5′), 7.16 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.24 (d, J5′,6′=8.4 Hz, 1H, Fe), 7.31 (s, 1H, H2′), 7.55 (d, J=15.6 Hz, 1H, CH═CHCO), 7.60 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 8.00 (d, J3,4=8.0 Hz, 1H, H3), 8.60 (d, J5,6=8.0 Hz, 1H, H6), 11.25 (s, 1H, NH), 13.57 (br s, 1H, CO2H); δC (100 MHz, DMSO-d6) 23.6, 32.2, 55.6, 79.5, 112.0, 113.6, 116.7, 119.9, 120.4, 122.2, 122.7, 127.2, 131.1, 134.0, 141.0, 141.6, 147.1, 151.5, 164.2, 169.4; HRMS (ESI) calculated for C22H23NO5 [M+Na]+ 404.1468. found 404.1468; vmax 751, 1254, 1504, 1583, 1661, 2948, 3516 cm−1.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][CH2:13][C@H:14]2[N:17]([CH3:19])[CH3:18])=[CH:10][CH:9]=1.O.[CH3:21][N:22]1[C:26]([CH3:27])=[C:25](B2OC(C)(C)C(C)(C)O2)[C:24]([CH3:37])=[N:23]1>COCCOC.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>[CH3:18][N:17]([CH3:19])[C@H:14]1[C:15]2[C:11](=[CH:10][CH:9]=[C:8]([C:25]3[C:24]([CH3:37])=[N:23][N:22]([CH3:21])[C:26]=3[CH3:27])[CH:16]=2)[CH2:12][CH2:13]1
Reactant: CN(C)[C@@H]1CCc2ccc(Br)cc21
Reactant: Cc1nn(C)c(C)c1B1OC(C)(C)C(C)(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: Cc1nn(C)c(C)c1-c1ccc2c(c1)[C@H](N(C)C)CC2
Temperature: 85 °C
Reaction time: 6 h
Yield: 52 %

Procedure:
(Method 1): To a solution of K2CO3 (1.9 mmol) and (R)-(6-bromo-indan-1-yl)-dimethyl-amine (1 mmol) in 1,2-dimethoxyethane (8.8 mL)/water (1.2 mL) was added Pd(PPh3)4 (0.1 mmol) and 1,3,5-trimethyl-1H-pyrazole-4-boronic acid pinacol ester (1.2 mmol). The reaction mixture was degassed and stirred at 85° C. for 6 h. The solvent was evaporated, crude was redissolved in dichloromethane and filtered through a pad of Celite. The filtrate was extracted with 6M HCl (3×0.16 mL). The aqueous layer was basified with 6M NaOH to pH 13 and extracted with dichloromethane. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Crude was purified by flash chromatography (CH2Cl2-MeOH-NEt3 as eluents) to yield (1R)-dimethyl-[6-(1,3,5-trimethyl-1H-pyrazol-4-yl)-indan-1-yl]-amine as an oil (52% yield). Product was obtained with a final ee of 99.6% (determined by chiral HPLC).
Reaction SMILES: [CH3:1][C:2]1[C:31]([CH3:32])=[CH:30][CH:29]=[CH:28][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([N:10]1[C:19]2[C:14](=[C:15](C3C=CC(CO)=CC=3)[CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12][CH2:11]1)=[O:9].OCC1C=CC(B(O)O)=CC=1.[CH3:44][S:45][C:46]1[N:51]=[C:50]([CH2:52][N:53]2[CH:57]=[C:56](B3OC(C)(C)C(C)(C)O3)[CH:55]=[N:54]2)[CH:49]=[CH:48][N:47]=1>>[CH3:1][C:2]1[C:31]([CH3:32])=[CH:30][CH:29]=[CH:28][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([N:10]1[C:19]2[C:14](=[C:15]([C:56]3[CH:55]=[N:54][N:53]([CH2:52][C:50]4[CH:49]=[CH:48][N:47]=[C:46]([S:45][CH3:44])[N:51]=4)[CH:57]=3)[CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12][CH2:11]1)=[O:9]
Reactant: CSc1nccc(Cn2cc(B3OC(C)(C)C(C)(C)O3)cn2)n1
Reactant: Cc1cccc(OCCCC(=O)N2CCCc3c(-c4ccc(CO)cc4)cccc32)c1C
Agent: OCc1ccc(B(O)O)cc1
Product: CSc1nccc(Cn2cc(-c3cccc4c3CCCN4C(=O)CCCOc3cccc(C)c3C)cn2)n1

Procedure:
The title compound was prepared using a procedure analogous to 4-(2,3-dimethylphenoxy)-1-(5-(4-(hydroxymethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)butan-1-one except that 4-(hydroxymethyl)phenylboronic acid was replaced with 2-(methylthio)-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)pyrimidine. LCMS, [M+H]+=528.4. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=5.3 Hz, 1H), 7.62 (s, 1H), 7.46 (s, 1H), 7.16-7.25 (m, 3H), 7.02 (t, J=7.8 Hz, 1H), 6.74 (d, J=7.5 Hz, 1H), 6.69 (d, J=5.1 Hz, 1H), 6.65 (d, J=8.4 Hz, 1H), 5.40 (s, 2H), 3.94 (t, J=5.5 Hz, 2H), 3.81 (t, J=6.8 Hz, 2H), 2.79 (t, J=7.2 Hz, 2H), 2.54-2.63 (m, 5H), 2.11-2.26 (m, 5H), 1.82-1.97 (m, 5H).
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:22]([C:24]2[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[C:26]([O:32][CH3:33])[CH:25]=2)[OH:23])[CH:17]=[C:18]([O:20][CH3:21])[CH:19]=1.[Cr]([O-])([O-])(=O)=O>ClCCl.CCOCC>[CH3:33][O:32][C:26]1[CH:25]=[C:24]([C:22]([C:16]2[CH:17]=[C:18]([O:20][CH3:21])[CH:19]=[C:14]([O:13][CH3:12])[CH:15]=2)=[O:23])[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=1
Reactant: COc1cc(OC)cc(C(O)c2cc(OC)cc(OC)c2)c1
Agent: O=[Cr](=O)([O-])Cl
Agent: O=[Cr](=O)([O-])[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: COc1cc(OC)cc(C(=O)c2cc(OC)cc(OC)c2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 63 %

Procedure:
Pyridinium chlorochromate (PCC) (12.9 g, 30 mmol) was suspended in 30 mL dichloromethane in a 200 mL round bottom flask. Crude bis(3,5-dimethoxyphenyl)methanol from above (compound A) was suspended in 30 mL dichloromethane then added to the chromate suspension. The dark solution was allowed to stir at ambient temperature for 18 hours then diluted with ether. After decantation, the organic solution was washed twice with 1N NaOH, twice with 10% HCl, saturated NaHCO3, and then with brine. It was dried over anhydrous MgSO4, filtered and concentrated to give a brownish yellow solid. The brownish yellow solid was purified by column chromatography using 50% acetone/hexane as eluent giving the product as a yellow solid in 63% yield over 2 steps: IR (cm−1): 2960, 2938, 2834, 1660, 1592, 1456, 1425, 1349, 1304, 1205, 1157, 1066, 744; 1H NMR (250 MHz, C6D6): δ 3.21 (s, 12H), 6.67 (t, J=2.2 Hz, 2H), 7.21 (d, J=2.5 Hz, 4H); 13C NMR (63 MHz, C6D6): 54.9 (4C), 105.3 (2C), 108.0 (4C), 140.2 (2C), 161.1 (4C), 195.2.
Reaction SMILES: [CH:1]1[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.[C:17](Cl)([CH3:20])([CH3:19])[CH3:18].[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl.O>[C:17]([C:8]1[C:7]2[C:16]3=[C:15]4[C:4](=[CH:5][CH:6]=2)[CH:3]=[CH:2][CH:1]=[C:14]4[CH:13]=[CH:12][C:11]3=[CH:10][CH:9]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: c1cc2ccc3cccc4ccc(c1)c2c34
Reactant: CC(C)(C)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)c1ccc2ccc3cccc4ccc1c2c34
Temperature: 0 °C
Reaction time: 2 h
Yield: 51.1 %

Procedure:
In a reaction vessel, 50.0 g (0.25 mol) of pyrene, 27.6 g (0.30 mol) of tert-butyl chloride, and 200 ml of methylene chloride were charged, and the resulting mixture was cooled to 0° C. Next, 35.3 g (0.27 mol) of aluminum chloride was charged, followed by stirring at room temperature for 2 hours. Then, iced water and methylene chloride were added, and an organic layer was extracted, washed with water, dried over magnesium sulfate, and recrystallized to produce 33 g of tert-butylpyrene crystals in a yield of 51%.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4](O)=[O:5].CN(C=O)C.C(Cl)(=O)C([Cl:21])=O>C(Cl)Cl>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4]([Cl:21])=[O:5]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1c(F)cc(F)cc1F
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1c(F)cc(F)cc1F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a DCM 200 mL solution of 2,4,6-trifluorobenzoic acid (20 g, 0.11 mol) and DMF (0.5 mL, 6.46 mmol) was added oxalyl chloride (21.6 g, 0.17 mol) dropwise. The reaction mixture was stirred at room temperature for 1 hr and the solvent was removed under reduced pressure to give the title compound as crude product (22 g).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[S]Cl.[C:11](=[S:13])=[S:12]>C(O)(=O)C.CCCCCC>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]2[N:6]=[C:11]([SH:13])[S:12][C:4]=2[CH:3]=1
Reactant: S=C=S
Reactant: Nc1ccc(Cl)cc1
Agent: [S]Cl
Solvent: CC(=O)O
Solvent: CCCCCC
Product: Sc1nc2ccc(Cl)cc2s1
Temperature: 60 °C

Procedure:
To a stirred solution of 4-chloroaniline (2.55 g) in acetic acid (5 cm3) was added sulphur monochloride (10 cm3) causing formation of a thick red slurry. The reaction was heated at 60° C. for 4 hours giving a mixture of green solid and a green solution. The mixture was diluted with hexane and the green solid was filtered off. The solid was taken into water and 2M NaOH was added and the mixture heated for 4 hours at 100° C. and then filtered through celite to give a pale pink filtrate. Carbon disulphide (2 cm3) was added to the filtrate and the reaction was heated at reflux for 15 hours. The mixture was cooled and acidlied to pH 1 causing formation of a thick yellow precipitate. Filtration and recrystallisation from ethanol/acetone/water gave 6-chloro-2-mercaptobenzthiazole as a white solid. 1H NMR (DMSO): d 7.97 (1H, d), 7.58 (1H, dd), 7.41 (1 H, d). Mp 251°-253° C. (dec).