Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C@H:4]([C:28](N1[C@@H](CC2C=CC=CC=2)COC1=O)=[O:29])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[O:13][C:12]([CH2:14][C:15]3[N:16]=[C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[O:18][C:19]=3[CH3:20])=[CH:11][C:10]=2[CH:27]=1)[CH3:2].[OH-:43].[Li+]>O1CCCC1>[CH2:1]([O:3][C@@H:4]([CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[O:13][C:12]([CH2:14][C:15]3[N:16]=[C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[O:18][C:19]=3[CH3:20])=[CH:11][C:10]=2[CH:27]=1)[C:28]([OH:29])=[O:43])[CH3:2]
Reactant: CCO[C@@H](Cc1ccc2oc(Cc3nc(-c4ccccc4)oc3C)cc2c1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Reactant: [OH-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCO[C@@H](Cc1ccc2oc(Cc3nc(-c4ccccc4)oc3C)cc2c1)C(=O)O
Temperature: 0 °C

Procedure:
5-{(S)-2-Ethoxy-3-[(S)-4-benzyl-2-oxo-3-oxazolidinyl}-3-oxopropyl}-2-[(5-methyl-2-phenyl-4-oxazolyl)methyl]benzofuran (0.15 g, 0.26 mmol) was dissolved in tetrahydrofuran (5 ml). The solution was cooled to 0° C. and 0.5N lithium hydroxide (1.1 ml, 0.52 mmol) was added. After 15 minutes the bulk of the ethanol was removed, the residue was acidified with 1N HCl, diluted with water and extracted with ethyl acetate (3×). The combined extracts were washed with brine, dried over sodium sulfate and concentrated. The product was purified by flash-chromatography (hexanes/ethyl acetate/acetic acid, 10:10:1) then recrystallized from hexanes/ethyl acetate and obtained as a white solid (48 mg, mp 129° C., [α]D =-12.5° (c 0.99, CDCl3)).
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[C:13]([O:17][C:18](=[O:27])[NH:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)([CH3:16])([CH3:15])[CH3:14].[OH-].[K+]>CS(C)=O>[C:13]([O:17][C:18](=[O:27])[NH:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=2[N+:10]([O-:12])=[O:11])=[CH:24][CH:25]=1)([CH3:16])([CH3:14])[CH3:15]
Reactant: CC(C)(C)OC(=O)Nc1ccc(O)cc1
Reactant: O=Cc1ccc(Cl)c([N+](=O)[O-])c1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)Nc1ccc(Oc2ccc(C=O)cc2[N+](=O)[O-])cc1

Procedure:
A mixture of 4-chloro-3-nitrobenzaldehyde and (4-Hydroxy-phenyl)-carbamic acid tert-butyl ester were reacted together in DMSO with addition of KOH to provide the title product.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[C:5]#[N:6].[C:12](#[N:14])[CH3:13].C1COCC1.CC(C)([O-])C.[K+]>C([O-])(O)=O.[Na+]>[NH2:6][C:5]([C:4]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:2]([F:1])[CH:3]=1)=[CH:13][C:12]#[N:14]
Reactant: CC#N
Reactant: COc1ccc(C#N)cc1F
Agent: CC(C)(C)[O-]
Agent: O=C([O-])O
Agent: [K+]
Solvent: C1CCOC1
Product: COc1ccc(C(N)=CC#N)cc1F
Reaction time: 8 h
Yield: 78.6 %

Procedure:
Combine 3-fluoro-4-methoxybenzonitrile (25.000 g, 165.563 mmol) and acetonitrile (13.576 g, 331.126 mmol) and THF (33 mL). Add potassium t-butoxide in THF (1 M, 182.1 mL, 182.1 mmol) with stirring. Stir overnight. Dilute with satd NaHCO3 and extract with EtOAc. Evaporate the organic solution and crystallize from hexane/EtOAc to afford 3-amino-3-(3-fluoro-4-methoxyphenyl)acrylonitrile. Yield: 78.6%. ES-MS: m/e 193.0 (m+1).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([CH3:12])[C@@H:11]2[C@@H:9]([O:10]2)[CH2:8][CH2:7][CH2:6]1)=[O:4].CO.[NH4+].[Cl-].[N-:17]=[N+:18]=[N-:19].[Na+]>O>[CH3:1][O:2][C:3]([C:5]1([CH3:12])[CH2:6][CH2:7][CH2:8][CH:9]([N:17]=[N+:18]=[N-:19])[CH:11]1[OH:10])=[O:4]
Reactant: COC(=O)C1(C)CCC[C@@H]2O[C@@H]21
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COC(=O)C1(C)CCCC(N=[N+]=[N-])C1O

Procedure:
Racemic cis-methyl-5-methyl-7-oxabicyclo[4.1.0]heptane-5-carboxylate, 66b, (2.2 g, 12.93 mmol) was added to a flask containing MeOH (90 mL) and H2O (10 mL) under nitrogen atmosphere. NH4Cl (1.38 g, 0.90 mL, 25.86 mmol) and NaN3 (2.52 g, 38.79 mmol) were then added to the reaction mixture. The mixture was heated to reflux for 16 hours. The solvent was evaporated under reduced pressure and the oil was taken up in H2O and extracted with EtOAc. The combined organic phases were washed with brine and dried over Na2SO4. The crude product was purified by silica gel chromatography to afford 900 mg of racemic methyl-3-azido-2-hydroxy-1-methyl-cyclohexanecarboxylate.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][NH2:9])[CH:5]=[N:4][CH:3]=[N:2]1.O1CCCC1.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]=[C:23]=[O:24])=[CH:18][CH:17]=1>C1(C)C=CC=CC=1>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:9][CH2:8][CH2:7][CH2:6][N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)=[O:24])=[CH:18][CH:17]=1
Reactant: O=C=Nc1ccc(Cl)cc1
Reactant: NCCCn1cncn1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: O=C(NCCCn1cncn1)Nc1ccc(Cl)cc1
Reaction time: 8 h

Procedure:
A 1.26 g. portion of 1H-1,2,4-triazole-1-propanamine was suspended in 15 ml. of toluene and 5 ml. of tetrahydrofuran was added to produce solution. A solution of 1.55 g. of freshly distilled p-chlorophenyl isocyanate in 15 ml. of toluene was added and the mixture was stirred overnight. The resulting crystals were recrystallized from toluene, giving 2.06 g. of the desired product, mp. 137°-139° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[C:10]2[C:20](=[O:21])[NH:19][CH:18]=[CH:17][C:11]=2[N:12]=[C:13](SC)[N:14]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[NH2:33][CH2:34][CH2:35][CH2:36][NH:37]C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>>[NH2:33][CH2:34][CH2:35][CH2:36][NH:37][C:13]1[N:14]=[C:9]([NH:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])[C:10]2[C:20](=[O:21])[NH:19][CH:18]=[CH:17][C:11]=2[N:12]=1
Reactant: CC(C)(C)OC(=O)NCCCN
Reactant: CSc1nc(Nc2ccccc2C)c2c(=O)[nH]ccc2n1
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccccc1Nc1nc(NCCCN)nc2cc[nH]c(=O)c12

Procedure:
The compound was prepared from 4-[(2-methylphenyl)amino]-2-(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one following a procedure (mCPBA/1,1-dimethylethyl (3-aminopropyl)carbamate and TFA) similar to that described for Example 1 (Scheme 2).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.[CH3:13][N:14]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=1)[CH3:15]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH2:9][C:10]([NH:23][C:20]2[CH:19]=[CH:18][C:17]([CH2:16][N:14]([CH3:15])[CH3:13])=[CH:22][CH:21]=2)=[O:12])=[CH:6][CH:7]=1
Reactant: CN(C)Cc1ccc(N)cc1
Reactant: O=C(O)CNc1ccc(Br)cc1
Product: CN(C)Cc1ccc(NC(=O)CNc2ccc(Br)cc2)cc1

Procedure:
The product was prepared according to general working method I from (4-bromo-phenylamino)-acetic acid and 4-dimethylaminomethyl-phenylamine.
Reaction SMILES: [Br:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1S(C)=O.[CH2:17]([OH:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1CCN2C(=NCCC2)CC1>O1CCOCC1>[CH2:17]([O:24][C:7]1[C:2]([Br:1])=[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)[N:4]=[C:5]([NH2:11])[N:6]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: OCc1ccccc1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1Br
Solvent: C1COCCO1
Solvent: C1CCC2=NCCCN2CC1
Product: Nc1nc(OCc2ccccc2)c(Br)c(-c2ccco2)n1

Procedure:
From 5-bromo-4-furan-2-yl-6-methanesulfinyl-pyrimidin-2-ylamine, benzylalcohol and DBU in dioxane. ES-MS m/e (%): 348 (M{81Br}+H+, 96), 346 (M{79Br}+H+, 100).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([N:12]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:13][C@H:14]([OH:23])[CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:10][OH:11])=[CH:4][CH:3]=1.[NH:31]1[CH:35]=[CH:34][CH:33]=[C:32]1[C:36](O)=[O:37].Cl.CN(C)CCCN=C=NCC>ClCCl>[CH2:24]([N:12]([C@H:9]([CH2:10][OH:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:36]([C:32]2[NH:31][CH:35]=[CH:34][CH:33]=2)=[O:37])=[CH:3][CH:4]=1)[CH2:13][C@H:14]([OH:23])[CH2:15][O:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: O=C(O)c1ccc[nH]1
Reactant: Nc1ccc(C[C@@H](CO)N(Cc2ccccc2)C[C@H](O)COc2ccccc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: O=C(Nc1ccc(C[C@@H](CO)N(Cc2ccccc2)C[C@H](O)COc2ccccc2)cc1)c1ccc[nH]1
Temperature: 25 °C
Reaction time: 47 h
Yield: 49.4 %

Procedure:
To a mixture of (2S)-3-(4-aminophenyl)-2-[N-benzyl-N-[(2S)-2-hydroxy-3-phenoxypropyl]amino]-1-propanol (79 mg) and pyrrole-2-carboxylic acid (26 mg) in dichloromethane (0.8 ml) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (59 mg), and the mixture was stirred at room temperature for 47 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate) to give N-[4-[(2S)-2-[N-benzyl-N-[(2S)-2-hydroxy-3-phenoxypropyl]amino]-3-hydroxypropyl]-phenyl]-1H-pyrrole-2-carboxamide (48 mg) as a white amorphous powder.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[C:12]([CH3:22])=[C:13]([CH:18]=[CH:19][C:20]=2[CH3:21])[C:14]([O:16][CH3:17])=[O:15])=[O:9])[C:5]([CH3:23])=[CH:4][CH:3]=1.[CH3:24][C:25]1([OH:31])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:31][C:25]1([CH3:24])[CH2:30][CH2:29][N:28]([C:2]2[N:7]=[C:6]([C:8]([NH:10][C:11]3[C:12]([CH3:22])=[C:13]([CH:18]=[CH:19][C:20]=3[CH3:21])[C:14]([O:16][CH3:17])=[O:15])=[O:9])[C:5]([CH3:23])=[CH:4][CH:3]=2)[CH2:27][CH2:26]1
Reactant: CC1(O)CCNCC1
Reactant: COC(=O)c1ccc(C)c(NC(=O)c2nc(Cl)ccc2C)c1C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: COC(=O)c1ccc(C)c(NC(=O)c2nc(N3CCC(C)(O)CC3)ccc2C)c1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 58.1 %

Procedure:
To a solution of methyl 3-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-2,4-dimethyl-benzoate (315 mg, 946.55 mmoles), 4-methylpiperidin-4-ol (130 mg, 1.13 mmol) and Cs2CO3 (0.9 g, 2.76 mmol) in 1,4-dioxane (7 ml) is added Pd(OAc)2 (25 mg, 89.93 moles) followed by racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (56 mg, 89.93 moles). The reaction mixture is purged with nitrogen for 5 minutes and then heated to reflux. After 2 hours, the reaction is cooled to ambient temperature and diluted with ammonium chloride and extracted with EtOAc. The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using 0-100% ethyl acetate in hexane to afford the title compound as a brown solid (0.27 g, 69%). Mass spectrum (m/z): 412.2 (M+1).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[C:16]([Sn](C)(C)C)[N:15]=[C:14]([C:22]#[N:23])[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:24][C:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1Br)([F:27])[F:26]>CN(C)C=O.C(OCC)(=O)C.O>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[C:16]([C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([C:25]([F:27])([F:26])[F:24])[CH:29]=2)[N:15]=[C:14]([C:22]#[N:23])[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: FC(F)(F)c1ccccc1Br
Reactant: C[Sn](C)(C)c1cc(CCCOCc2ccccc2)nc(C#N)n1
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#Cc1nc(CCCOCc2ccccc2)cc(-c2cccc(C(F)(F)F)c2)n1

Procedure:
A solution of 4-(3-benzyloxy-propyl)-6-trimethylstannanyl-pyrimidine-2-carbonitrile (100 mg), trifluoromethylbromobenzene (36□μL) and 1,1′-(bistriphenylphosphino)ferrocenedichloropalladium(II) (16 mg) in dimethylformamide (5 mL) was heated in microwave at 150° C. for 5 min. The resulting suspension was diluted with ethyl acetate and water (20 mL), the organic layer being separated, dried over sodium sulphate and evaporated at reduced pressure. Flash silica chromatography afforded 4-(3-benzyloxy-propyl)-6-(3-trifluoromethyl-phenyl)-pyrimidine-2-carbonitrile as a yellow gum (47 mg).
Reaction SMILES: [C:1]([NH:4][NH2:5])(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:15][C:16]1[C:21]([CH3:22])=[C:20]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][N:30]=3)[CH2:25][CH2:24]2)[N:19]=[N:18][C:17]=1[CH2:39][C:40](O)=[O:41].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:15][C:16]1[C:21]([CH3:22])=[C:20]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][N:30]=3)[CH2:25][CH2:24]2)[N:19]=[N:18][C:17]=1[CH2:39][C:40]([NH:5][NH:4][C:1](=[O:3])[CH3:2])=[O:41]
Reactant: CC(=O)NN
Reactant: Cc1c(CC(=O)O)nnc(N2CCN(c3ccc(C(F)(F)F)cn3)CC2)c1C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(=O)NNC(=O)Cc1nnc(N2CCN(c3ccc(C(F)(F)F)cn3)CC2)c(C)c1C
Reaction time: 1 h
Yield: 90.2 %

Procedure:
Acetic acid hydrazide (20.6 mg, 0.28 mmol) is added to a round-bottom flask under N2 followed by DMF (5 mL). Diisopropylethylamine (0.25 mL) is added and the reaction is stirred for 30 min. {4,5-Dimethyl-6-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyridazin-3-yl}-acetic acid (110 mg, 0.28 mmol) is added and the reaction is stirred for 1 h. HOBT (42 mg, 0.311 mmol) and HBTU (116.8 mg, 0.31 mmol) are added and the reaction is allowed to stir for 16 h. The crude reaction mixture is purified via flash chromatography on silica gel (0-30% methanol in dichloromethane) to afford the title compound (114 mg, 90%).
Reaction SMILES: [CH:1]1[C:14]2[CH:13]=[C:12](B(O)O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Br:18][C:19]1[CH:20]=[C:21]([C:26]2[N:31]=[C:30]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:29]=[C:28]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[N:27]=2)[CH:22]=[C:23](Br)[CH:24]=1.C1(C)C=CC=CC=1>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.C(O)C>[C:38]1([C:28]2[N:29]=[C:30]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:31]=[C:26]([C:21]3[CH:22]=[C:23]([C:12]4[C:11]5[C:6]([C:5]6[CH:4]=[CH:3][CH:2]=[CH:1][C:14]=6[CH:13]=4)=[CH:7][CH:8]=[CH:9][CH:10]=5)[CH:24]=[C:19]([Br:18])[CH:20]=3)[N:27]=2)[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1
Reactant: OB(O)c1cc2ccccc2c2ccccc12
Reactant: Brc1cc(Br)cc(-c2nc(-c3ccccc3)nc(-c3ccccc3)n2)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCO
Solvent: Cc1ccccc1
Product: Brc1cc(-c2nc(-c3ccccc3)nc(-c3ccccc3)n2)cc(-c2cc3ccccc3c3ccccc23)c1
Temperature: 25 °C
Yield: 30 %

Procedure:
In a stream of argon, 0.71 g (3.21 mmol) of 9-phenanthreneboronic acid, 1.50 g (3.21 mmol) of 2-(3,5-dibromophenyl)-4,6-diphenyl-1,3,5-triazine and 37.0 mg (0.0321 mmol) of tetrakis(triphenylphosphine)palladium were suspended in a mixed solvent composed of 120 mL of toluene and 15 mL of ethanol, and the resultant suspension was heated to 60° C. and maintained at that temperature for 12 hours while being stirred. The obtained reaction mixture was cooled to room temperature, and then distilled under a reduced pressure to remove all volatile materials. Methanol was added to the concentrate, and the thus-deposited solid was collected by filtration. The obtained crude product was purified by silica gel chromatography using a hexane/chloroform (2:1) mixed solvent as an eluent to give 0.54 g of the target 4,6-diphenyl-2-[5-(9-phenanthryl)-3-bromophenyl]-1,3,5-triazine as a white solid (yield: 30%).
Reaction SMILES: [C:1]([N:11]([C@@H:13]([CH3:21])[C:14]1[CH:19]=[CH:18][C:17](N)=[CH:16][CH:15]=1)[CH3:12])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].N([O-])=[O:23].[Na+].C1(C)C=CC=CC=1>S(=O)(=O)(O)O.O>[C:1]([N:11]([C@@H:13]([CH3:21])[C:14]1[CH:19]=[CH:18][C:17]([OH:23])=[CH:16][CH:15]=1)[CH3:12])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: C[C@@H](c1ccc(N)cc1)N(C)C(=O)OCc1ccccc1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: C[C@@H](c1ccc(O)cc1)N(C)C(=O)OCc1ccccc1
Temperature: 82.5 °C
Reaction time: 0.5 h
Yield: 58.4 %

Procedure:
The above (S)-(-)-N-carbobenzyloxy-N-methyl-4-amino-α-methylbenzylamine (6.0 gm, assume 21 mmol) was dissolved in 2N sulfuric acid (63 mL) and cooled in an ice salt bath. A solution of sodium nitrite (1.6 gm, 23 mmol) in water (25 mL) was added over 15 min at 0-5° C. and the reaction stirred for another 0.5 hr. Toluene (100 mL) was then added and the reaction was rapidly heated to 80-85° C. on a steam bath. The reaction turned very dark and after 10 min was poured onto ice and extracted with 2 portions of ether. The ether layers were each washed with brine, combined, dried over sodium sulfate and evaporated. The residue was purified by flash chromatography using 20-30% ethyl acetate/hexanes to give 3.5 gm (58%) of the title compound.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[C:8]([Br:10])[C:7]([OH:11])=[C:6]([Br:12])[CH:5]=1)=[O:3].C([O-])([O-])=O.[K+].[K+].[Br:19][CH2:20][CH2:21][CH2:22]Br>>[Br:19][CH2:20][CH2:21][CH2:22][O:11][C:7]1[C:6]([Br:12])=[CH:5][C:4]([C:2](=[O:3])[CH3:1])=[CH:9][C:8]=1[Br:10]
Reactant: CC(=O)c1cc(Br)c(O)c(Br)c1
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CC(=O)c1cc(Br)c(OCCCBr)c(Br)c1

Procedure:
A stirred mixture of 3,5-dibromo-4-hydroxyacetophenone (3.0 g, 10.1 mmole), K2CO3 (2.8 g, 20.3 mmoles), 1,3- dibromopropane (4.0 g, 19.8 moles) in acetnotrile (100 ml) was heated at reflux for 5 hr. The solvent was removed. The crude product was extracted into dichloromethane (150 ml) and the insoluble inorganics were filtered off. The solution was concentrated to dryness again. Purification was carried out by flash chromatography on silica gel (45 g, SiO2; eluted with 1:1 hexane:dichloromethane). The material thus obtained (2.8 g) was recrystallized twice from isopropyl ether to give analytically pure 1-[4-(3-bromopropoxy)-3,5- dibromophenyl]ethanone, m.p.=87°-88° C.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:17]([NH:19][CH2:20][C:21]2[C:22](=[O:29])[NH:23][C:24]([CH3:28])=[CH:25][C:26]=2[CH3:27])=[O:18])[C:6]2[CH:7]=[N:8][N:9]([CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[C:10]=2[CH:11]=1)#[N:2]>C(O)(=O)C.CO>[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([C:17]([NH:19][CH2:20][C:21]2[C:22](=[O:29])[NH:23][C:24]([CH3:28])=[CH:25][C:26]=2[CH3:27])=[O:18])[C:6]2[CH:7]=[N:8][N:9]([CH:12]3[CH2:13][CH2:14][CH2:15][CH2:16]3)[C:10]=2[CH:11]=1
Reactant: Cc1cc(C)c(CNC(=O)c2cc(C#N)cc3c2cnn3C2CCCC2)c(=O)[nH]1
Solvent: CC(=O)O
Solvent: CO
Product: Cc1cc(C)c(CNC(=O)c2cc(CN)cc3c2cnn3C2CCCC2)c(=O)[nH]1
Temperature: 40 °C

Procedure:
6-cyano-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.10 g, 0.257 mmol) was suspended in acetic acid (8 mL). The contents were placed heated at 40° C. under an atmosphere of hydrogen (50 psi; H-cube reactor) at a flow rate of 1 mL/min with recirculation 2 h. Then contents were diluted with MeOH, concentrated in vacuo, and dried under hi vacuum for 18 h. The crude product was dissolved in DCM and purified by silica gel chromatography (eluent: 10-100% gradient of chloroform (containing 10% 2M ammonia in methanol) and dichloromethane. The product was concentrated from MTBE and dried in a vacuum oven at 45° C. for 4 h. The title compound was collected as 68 mg (66%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.75 (m, 2H), 1.82-1.93 (m, 2H), 1.94-2.04 (m, 2H), 2.06-2.17 (m, 6H), 2.21 (s, 3H), 3.85 (s, 2H), 4.35 (d, J=5.05 Hz, 2H), 5.14 (t, J=7.07 Hz, 1H), 5.89 (s, 1H), 7.54 (s, 1H), 7.76 (s, 1H), 8.27 (s, 1H), 8.32 (t, J=5.05 Hz, 1H);
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[C:16]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]([OH:32])=O)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl.[CH2:34]([O:36][C:37](=[O:40])[CH2:38][NH2:39])[CH3:35].C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1>O1CCCC1>[CH2:34]([O:36][C:37](=[O:40])[CH2:38][NH:39][C:30](=[O:32])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][NH:24][C:16](=[O:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH3:35]
Reactant: CCOC(=O)CN
Reactant: O=C(O)CCCCCNC(=O)c1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOC(=O)CNC(=O)CCCCCNC(=O)c1ccccc1
Temperature: 0 °C

Procedure:
A solution of dicyclohexylcarbodiimide (112 mmoles) in anhydrous tetrahydrofuran (44 ml) was gradually added to a suspension of N-benzoyl-6-aminohexanoic acid (93.5 mmoles), prepared as described in example 1, glycine ethyl ester hydrochloride (112 mmoles), triethylamine (112 mmoles) and anhydrous 1-hydroxybenzotriazole (112 mmoles) in tetrahydrofuran (330 ml), kept under stirring at 0° C. The reaction mixture was brought at room temperature and kept under stirring for 16 hours.
Reaction SMILES: [CH2:1]1[NH:6][C:4](=[O:5])[NH:3][CH2:2]1.[CH2:7]([S:9](Cl)(=[O:11])=[O:10])[CH3:8]>>[CH2:7]([S:9]([N:3]1[CH2:2][CH2:1][NH:6][C:4]1=[O:5])(=[O:11])=[O:10])[CH3:8]
Reactant: CCS(=O)(=O)Cl
Reactant: O=C1NCCN1
Product: CCS(=O)(=O)N1CCNC1=O

Procedure:
A mixture of 29.2g of ethyleneurea and 43.7 g of ethane sulphonyl chloride is heated at 110° for 3 hrs under nitrogen. The reaction mixture is triturated with 30 ml methanol and filtered. The filtrate is evaporated off and the residue is dissolved in chloroform and chromatographed on a column of 750 g of silica gel. The fraction which eluted with 5% methanol in chloroform, is recrystallized from a mixture of methylene chloride and hexane to afford 1-ethylsulphonyl-2-oxo-tetrahydroimidazole which melts at 114°-116°.
Reaction SMILES: [CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Cl:6][C:7]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:8]=1[CH:9]=[O:10].O.C(OCC)(=O)C>C1COCC1.C(OCC)C>[CH:1]1([CH:9]([C:8]2[CH:11]=[CH:12][C:13]([Cl:15])=[CH:14][C:7]=2[Cl:6])[OH:10])[CH2:3][CH2:2]1
Reactant: O=Cc1ccc(Cl)cc1Cl
Reactant: Br[Mg]C1CC1
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: OC(c1ccc(Cl)cc1Cl)C1CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
17 ml (8.57 mmol) of 0.5N cyclopropylmagnesium bromide solution in THF were added to 1.00 g (5.71 mmol) of 2,4-dichlorobenzaldehyde in 20 ml of diethyl ether at 0° C., and the mixture was warmed to RT and stirred at RT overnight. The reaction mixture was added to water and ethyl acetate, the phases were separated, the aqueous phase was extracted twice with ethyl acetate, and the combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water) to result in 925 mg (74% of theory) of the title compound.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:15]([C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1)=[CH2:16]>COCCOC.O>[Br:8][C:4]1[CH:3]=[C:2]([C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:15]=[CH2:16])[CH:22]=2)[CH:7]=[CH:6][CH:5]=1
Reactant: C=Cc1cccc(B(O)O)c1
Reactant: Brc1cccc(Br)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: C=Cc1cccc(-c2cccc(Br)c2)c1
Temperature: 80 °C
Yield: 59.5 %

Procedure:
A solution of 1,3-dibromobenzene (5.3 mL, 43.9 mmol), potassium carbonate (14.0 g, 101 mmol) and 3-vinylphenylboronic acid (5 g, 33.8 mmol) in DME (100 mL) and water (20 mL) (in a pressure vessel) was sparged with nitrogen for 15 min. Pd(PPh3)3 (1.17 g, 1.014 mmol) was added and then the reaction was heated to 80° C. overnight. The reaction was cooled to r.t. and evaporated on the rotovap. The residue was diluted in EtOAc and washed with water then brine, dried over MgSO4, filtered and evaporated to give the crude material. The crude material was purified by flash chromatography on the Biotage (0-5% EtOAc:Hex) to give 3-bromo-3′-vinylbiphenyl (5.21 g, 20.10 mmol, 60% yield) as a clear liquid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 5.33 (d, J=10.79 Hz, 1H) 5.84 (dd, J=17.57, 0.75 Hz, 1H) 6.80 (dd, J=17.57, 10.79 Hz, 1H) 7.32 (t, J=7.78 Hz, 1H) 7.38-7.48 (m, 3H) 7.51 (dddd, J=13.24, 7.84, 1.76, 1.00 Hz, 2H) 7.56-7.61 (m, 1H) 7.76 (t, J=1.88 Hz, 1H).