Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([N:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:8]2[N:13]=[C:12](Cl)[N:11]=[C:10](Cl)[N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:22]1([NH:28][C:29]#[N:30])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[Na]>CC(C)=O.O>[C:1]1([N:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:8]2[N:13]=[C:12]([N:28]([C:29]#[N:30])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:11]=[C:10]([N:7]([C:8]#[N:9])[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N#CNc1ccccc1
Reactant: Clc1nc(Cl)nc(N(c2ccccc2)c2ccccc2)n1
Agent: [Na]
Solvent: CC(C)=O
Solvent: O
Product: N#CN(c1ccccc1)c1nc(N(C#N)c2ccccc2)nc(N(c2ccccc2)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 106.1 %

Procedure:
To a solution of 31.7g (0.10 mole) of a 2-diphenylamino-4,6-dichloro-s-triazine in 325 ml of acetone at room temperature was added dropwise to a solution of 0.20 mole of sodium phenylcyanamide in 100 ml of water over a 30 minute period. After stirring for 1 hour at room temperature, the reaction mixture was heated at reflux overnight. After cooling the reaction mixture was filtered. The residue was washed with water, acetone and dried to give 25.5g of crude product. Recrystallization from 1500 ml of acetonitrile gave 20.9g of pure DPNCT, m.p. 280°-284°.
Reaction SMILES: [CH3:1][C:2]([Si:5]([CH3:42])([CH3:41])[O:6][CH:7]([C:22]1[CH:27]=[CH:26][C:25]([O:28]CC2C=CC=CC=2)=[C:24]([NH:36][S:37]([CH3:40])(=[O:39])=[O:38])[CH:23]=1)[CH2:8][NH:9][C@@H:10]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:11]([OH:13])=[O:12])([CH3:4])[CH3:3]>CO.[Pd]>[CH3:4][C:2]([Si:5]([CH3:41])([CH3:42])[O:6][CH:7]([C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[C:24]([NH:36][S:37]([CH3:40])(=[O:38])=[O:39])[CH:23]=1)[CH2:8][NH:9][C@@H:10]([C:14]1[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=1)[C:11]([OH:13])=[O:12])([CH3:1])[CH3:3]
Reactant: COc1ccc([C@H](NCC(O[Si](C)(C)C(C)(C)C)c2ccc(OCc3ccccc3)c(NS(C)(=O)=O)c2)C(=O)O)cc1
Agent: [Pd]
Solvent: CO
Product: COc1ccc([C@H](NCC(O[Si](C)(C)C(C)(C)C)c2ccc(O)c(NS(C)(=O)=O)c2)C(=O)O)cc1
Reaction time: 0.67 h
Yield: 111.4 %

Procedure:
A solution of (R), (S)-α-[[2-[((1,1-dimethylethyl)dimethylsilyl)oxy]-2-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethyl]amino]-4-methoxy-benzeneacetic acid (4.04 g, 6.5 mmol) in MeOH (50 mL) containing 0.42 g of 10% Pd/C was sparged with H2 at 20° C. By TLC (10% MeOH/CH2Cl2), the reaction was complete after 40 minutes whereupon the reaction mixture was filtered and concentrated in vacuo to obtain 3.8 g of the title compound as a solid foam.
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])[C:8]1C=CC=CC=1.[N:21](OCCC(C)C)=[O:22]>C(O)(C)(C)C>[O:14]=[C:7]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:8]=[N:21][OH:22]
Reactant: CC(C)CCON=O
Reactant: O=C(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Product: O=C(C=NO)c1ccccc1

Procedure:
A flask was charged with potassium tert-butoxide (58 mmol) and 63 mL of tert-butyl alcohol. The mixture was stirred until a solution was formed, and a solution of the appropriate benzophenone (50 mmol) in 35 mL of tert-butyl alcohol added dropwise over 15 min. The reaction mixture was stirred for 1 hr, and the neat isoamyl nitrite (75 mmol) added over five min. The reaction mixture was monitored for completion and then diluted with 100 mL of heptanes. The resulting solid (38 mmol) was collected via suction filtration and dried to a constant weight under vacuum. Procedure was adapted from: Hagedorn et al., Chem. Ber., 98:193 (1965).
Reaction SMILES: [CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([O:24][CH2:25][C@@H:26]5[CH2:28][O:27]5)=[C:19]([CH2:29][CH3:30])[CH:18]=4)[N:13]=3)[CH:9]=[C:8]([O:31][CH3:32])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([O:35][C:36](=[O:41])[CH2:37][CH2:38][NH:39][CH3:40])C>>[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([O:24][CH2:25][C@@H:26]([OH:27])[CH2:28][N:39]([CH3:40])[CH2:38][CH2:37][C:36]([OH:41])=[O:35])=[C:19]([CH2:29][CH3:30])[CH:18]=4)[N:13]=3)[CH:9]=[C:8]([O:31][CH3:32])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CCOC(=O)CCNC
Reactant: CCc1cc(-c2noc(-c3cc(OC)nc(C4CCCC4)c3)n2)cc(C)c1OC[C@@H]1CO1
Product: CCc1cc(-c2noc(-c3cc(OC)nc(C4CCCC4)c3)n2)cc(C)c1OC[C@@H](O)CN(C)CCC(=O)O

Procedure:
The title compound is prepared starting from (S)-5-(2-cyclopentyl-6-methoxypyridin-4-yl)-3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazole and ethyl-3-(methylamino)-propanoate in analogy to Example 9; LC-MS: tR=0.95 min, [M+H]+=539.53; 1H NMR (CDCl3): δ 7.84 (s, 1H), 7.82 (s, 1H), 7.48 (s, 1H), 7.27 (s, 1H), 6.49 (s br, 2H), 4.52-4.60 (m, 1H), 4.00 (s, 3H), 3.90-3.96 (m, 1H), 3.84-3.90 (m, 1H), 3.41-3.51 (m, 2H), 3.18-3.39 (m, 3H), 2.97 (s, 3H), 2.68-2.80 (m, 4H), 2.36 (s, 3H), 2.04-2.14 (m, 2H), 1.82-1.94 (m, 4H), 1.68-1.78 (m, 2H), 1.30 (t, J=7.5 Hz, 3H).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][CH2:6][C:7]1[N:8]=[C:9]2[C:14](=[C:15]3[C:20]=1[CH:19]=[CH:18][CH:17]=[CH:16]3)[CH:13]=[CH:12][CH:11]=[CH:10]2)=[O:4].[NH:21]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28][NH:27][CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH:13]1[C:14]2[C:9](=[N:8][C:7]([CH2:6][NH:5][C:3](=[O:4])[CH2:2][N:21]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28][NH:27][CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[C:20]3[C:15]=2[CH:16]=[CH:17][CH:18]=[CH:19]3)[CH:10]=[CH:11][CH:12]=1
Reactant: O=C(CCl)NCc1nc2ccccc2c2ccccc12
Reactant: C1CNCCNCCNCCN1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: O=C(CN1CCNCCNCCNCC1)NCc1nc2ccccc2c2ccccc12
Temperature: 25 °C
Yield: 47.1 %

Procedure:
A solution of the chloro 9 (20.0 mg, 70.2 μmol) in anhydrous CHCl3 (5 mL) was added to a solution of cyclen (48.4 mg, 0.281 mmol) and triethylamine (11.7 μL, 84.2 μmol) in anhydrous CHCl3 (15 mL) under N2 (g). The reaction mixture was heated to reflux under N2 (g) for 23 hours. The reaction mixture was then allowed to cool to room temperature and washed with NaOH (aq) (1.0 M, 3×5 mL) and H2O (3×5 mL). The organic phase was dried over MgSO4, and concentrated under reduced pressure yielding product 10 as a colorless oil (13.9 mg, 47.1%). This procedure follows closely that developed by Gunnlaugsson and coworkers. (Massue et al. Tetrahedron Lett., 2007, 48, 8052-8055).
Reaction SMILES: [CH:1]1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([CH2:12][CH2:13][CH2:14][C:15]([O:17]CC)=[O:16])[C:5]=2[CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].Cl>CO>[CH:1]1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)CCCC1CCCCc2ccccc21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)CCCC1CCCCc2ccccc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of ethyl 4-(6,7,8,9-tetrahydro-5H-5-benzocycloheptenyl)butyrate (0.534 g) in methanol (10 ml) was added with 2 N aqueous sodium hydroxide (2 ml), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was added with 2 N aqueous hydrochloric acid and thereby made acidic, and the mixture was extracted with chloroform. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to quantitatively obtain the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:14])[CH:5]([C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1)[CH3:6])[CH3:2].[C:15]([S-:17])#[N:16].[K+].BrBr>CC(O)=O>[CH2:1]([O:3][C:4](=[O:14])[CH:5]([C:7]1[CH:8]=[CH:9][C:10]2[N:13]=[C:15]([NH2:16])[S:17][C:11]=2[CH:12]=1)[CH3:6])[CH3:2]
Reactant: CCOC(=O)C(C)c1ccc(N)cc1
Reactant: N#C[S-]
Agent: BrBr
Agent: [K+]
Solvent: CC(=O)O
Product: CCOC(=O)C(C)c1ccc2nc(N)sc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 3 (3.13 g, 1 mmol) in CH3COOH (15 ml) was cooled to −5□ in iced bath. A mixture KSCN (6.36 g, 4.04 mmol) in CH3COOH (15 ml) added to the flask that contained 4 and CH3COOH at −5° in iced bath. A solution of bromine (0.80 ml) in CH3COOH (10 ml) is added dropwise to a stirred mixture of 4, KSCN and CH3COOH at −5° in iced bath. The reaction mixture is stirred for 1 h at room temperature. The mixture is extracted with ethyl acetate. The extracts are washed with water, brine, dried over magnesium sulfate, filtered and concentrated in vacuo.
Reaction SMILES: [CH3:1][C:2]([NH:8][CH2:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][C:11]=1[Cl:22])([CH3:7])[C:3]([O:5]C)=O.[F:23][C:24]([F:36])([F:35])[O:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]=[C:33]=[O:34])=[CH:28][CH:27]=1>>[CH3:7][C:2]1([CH3:1])[N:8]([CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[Cl:22])[C:33](=[O:34])[N:32]([C:29]2[CH:28]=[CH:27][C:26]([O:25][C:24]([F:23])([F:35])[F:36])=[CH:31][CH:30]=2)[C:3]1=[O:5]
Reactant: O=C=Nc1ccc(OC(F)(F)F)cc1
Reactant: COC(=O)C(C)(C)NCc1c(Cl)cnc2ccc(OC)cc12
Product: COc1ccc2ncc(Cl)c(CN3C(=O)N(c4ccc(OC(F)(F)F)cc4)C(=O)C3(C)C)c2c1

Procedure:
The product is prepared according to the procedure described in Example 59, starting with 180 mg of methyl 2-methyl-2-[(3-chloro-6-methoxyquinol-4-ylmethyl)amino]propanoate instead of methyl 2-methyl-2-[(quinol-4-ylmethyl)amino]propanoate used in Example 59 and 267 mg of 4-(trifluoromethoxy)phenyl isocyanate. After purification by flash chromatography on a column (SiO2, 80/20 cyclohexane/EtOAc by volume as eluent, Ar), 137 mg of the expected product are obtained.
Reaction SMILES: [NH:1]1[C:5]([C:6]2[C:7]3[CH2:15][CH2:14][N:13]([C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[C:19]=4[Cl:28])=[O:17])[CH2:12][C:8]=3[N:9]=[CH:10][N:11]=2)=[CH:4][CH:3]=[N:2]1.[H-].[Na+].[CH3:31]I>CN(C=O)C.O>[Cl:28][C:19]1[C:20]([C:24]([F:25])([F:27])[F:26])=[CH:21][CH:22]=[CH:23][C:18]=1[C:16]([N:13]1[CH2:14][CH2:15][C:7]2[C:6]([C:5]3[CH:4]=[CH:3][N:2]([CH3:31])[N:1]=3)=[N:11][CH:10]=[N:9][C:8]=2[CH2:12]1)=[O:17]
Reactant: O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(ncnc2-c2ccn[nH]2)C1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1ccc(-c2ncnc3c2CCN(C(=O)c2cccc(C(F)(F)F)c2Cl)C3)n1
Yield: 44 %

Procedure:
To a solution of Example 18 (137 mg, 0.33 mmol) in DMF (3 mL) was added NaH, 60% dispersion in mineral oil (16 mg, 0.40 mmol). After 30 minutes MeI (0.03 mL, 0.40 mmol) was then added. After several hours the reaction was diluted with water and then extracted with EtOAc. The combined organic layers were washed with water, dried over Na2SO4, filtered and concentrated in vacuo. Purification on a Prep Agilent system with a XBridge C18 OBD 50×100 mm column eluting with 5 to 99% 0.05% NH4OH in H2O/ACN over 17 min to afforded the title compound as a white solid (61.2 mg, 43%). MS (ESI) mass calcd. C19H15ClF3N5O, 421.09. m/z found 422.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 9.09-8.92 (m, 1H), 7.82-7.75 (m, 1H), 7.58-7.42 (m, 3H), 7.06-7.01 (m, 1H), 5.19-4.92 (m, 1H), 4.58-4.38 (m, 1H), 4.22-3.94 (m, 4H), 3.57-3.22 (m, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.C([Li])CCC.[O:17]=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1>C(Cl)Cl>[OH:17][C:18]1([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=2)[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: FC(F)(F)c1ccnc(Br)c1
Agent: [Li]CCCC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(O)(c2cc(C(F)(F)F)ccn2)CC1
Temperature: -78 °C
Reaction time: 0.67 h
Yield: 58.9 %

Procedure:
To a slightly cloudy solution of 2-bromo-4-(trifluoromethyl)pyridine (4.0 g, 14.2 mmol) in dry methylene chloride (52.7 mL) cooled at −78° C. was added a 1.6 M solution of n-butyllithium in hexanes (9.65 mL). After being stirred for 40 min at −78° C., a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (2.59 g, 12.9 mmol) in dry methylene chloride (10.0 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h and quenched with aqueous NH4Cl. THF was removed by rotary evaporation. The aqueous layer was extracted with methylene chloride three times. The combined organic layers were dried, filtered and concentrated. The residue was purified by column chromatography on silica gel (30:70 EtOAc/hexanes) to give 2.63 g (59%) of desired product as a brown oil. LC-MS calculated for C16H21F3N2O3: (M+H) 347; found 247.0 (M-Boc+1).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([O:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11](O)=[O:12])=[CH:7]2.[CH2:25]([S:32][CH:33]([CH:36]([O:39][CH3:40])[O:37][CH3:38])[CH2:34][NH2:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH2:25]([S:32][CH:33]([CH:36]([O:37][CH3:38])[O:39][CH3:40])[CH2:34][NH:35][C:11]([C:8]1[NH:9][C:10]2[C:6]([CH:7]=1)=[CH:5][C:4]([O:14][C:15]1[CH:16]=[CH:17][C:18]([S:21]([CH3:24])(=[O:22])=[O:23])=[CH:19][CH:20]=1)=[CH:3][C:2]=2[OH:1])=[O:12])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: COC(OC)C(CN)SCc1ccccc1
Reactant: CS(=O)(=O)c1ccc(Oc2cc(O)c3[nH]c(C(=O)O)cc3c2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: COC(OC)C(CNC(=O)c1cc2cc(Oc3ccc(S(C)(=O)=O)cc3)cc(O)c2[nH]1)SCc1ccccc1
Temperature: 0 °C
Yield: 50.1 %

Procedure:
To an ice-cooled and stirred mixture of 7-hydroxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylic acid (2.1 g) and 2-(benzylsulfanyl)-3,3-dimethoxypropan-1-amine (2.9 g) in N,N-dimethylformamide (50 mL) were added 1-hydroxybenzotriazole (1.1 g), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.6 g). After stirred at 4° C. to room temperature for 15 h, the reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (ethyl acetate:hexane=35:65 to 60:40, volume ratio) to give light yellow crystals, which were washed with ethyl acetate-hexane to give the title compound (1.73 g, 50%) as pale yellow needles. MS 569 (MH+).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([N+:15]([O-:17])=[O:16])[CH:14]=1)[NH:11][C:10]([C:18]([O:20]CC)=[O:19])=[CH:9]2.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C.O1CCCC1.[OH-].[Na+]>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([N+:15]([O-:17])=[O:16])[CH:14]=1)[NH:11][C:10]([C:18]([OH:20])=[O:19])=[CH:9]2
Reactant: CCOC(=O)c1cc2cc(OCCOC)cc([N+](=O)[O-])c2[nH]1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: COCCOc1cc([N+](=O)[O-])c2[nH]c(C(=O)O)cc2c1
Temperature: 50 °C
Reaction time: 1.5 h
Yield: 97.2 %

Procedure:
Ethyl 5-(2-methoxyethoxy)-7-nitro-1H-indole-2-carboxylate (7.7 g) was dissolved in a mixed solvent of ethanol (75 mL) and tetrahydrofuran (75 mL), 1N aqueous sodium hydroxide solution (75 mL) was added to this solution, and the mixture was stirred at 50° C. for 1.5 hr. Aqueous citric acid solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The obtained crude product was crystallized from ethyl acetate-hexane to give the title compound (6.8 g, yield 97%) as yellow crystals. melting point 192-193° C.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]1[C:7]([CH2:18][CH:19]([CH3:21])[CH3:20])=[N:8][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[C:10]=1[CH3:11])C.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1>[CH2:18]([C:7]1[C:6]([CH2:5][CH:4]=[O:3])=[C:10]([CH3:11])[N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[N:8]=1)[CH:19]([CH3:21])[CH3:20]
Reactant: CCOC(=O)Cc1c(CC(C)C)nn(-c2ccccn2)c1C
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: C1CCOC1
Product: Cc1c(CC=O)c(CC(C)C)nn1-c1ccccn1
Temperature: -78 °C
Reaction time: 6 h

Procedure:
Dissolve (3-isobutyl-5-methyl-1-pyridin-2-yl-1H-pyrazol-4-yl)-acetic acid ethyl ester (3.35 g, 11.11 mmol) in tetrahydrofuran (50 mL) and cool to −78° C. Add diisobutylaluminum hydride (33.3 mL, 33.3 mmol, 1 M in toluene) dropwise. Continue stirring at −78° C. for 6 hr. Quench with saturated aqueous potassium sodium tartrate solution (50 mL) and warm to room temperature over 16 hr. Extract with ethyl acetate (2×100 mL). Combine organic layers, dry (sodium sulfate), filter and concentrate. Purify using silica gel chromatography, eluting with 90:10 hexanes:ethyl acetate, to give the title preparation (1.60 g, 56%). 1H-NMR (400 MHz, CDCl3) δ 9.62 (t, 1H), 8.39 (m, 1H), 7.77 (m, 2H), 7.15 (m, 1H), 3.45 (d, 2H), 2.96 (d, 2H), 2.22 (s, 3H), 1.80 (m, 1H), 0.81 (d, 6H).
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[OH-].[Na+].Br[CH2:16][CH2:17][CH2:18][Cl:19]>CO>[Cl:19][CH2:18][CH2:17][CH2:16][O:12][C:9]1[CH:10]=[CH:11][C:6]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:7][CH:8]=1
Reactant: ClCCCBr
Reactant: Oc1ccc(-n2ccnc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: ClCCCOc1ccc(-n2ccnc2)cc1
Temperature: 70 °C
Reaction time: 18 h
Yield: 20.3 %

Procedure:
To a stirring solution of 4-(imidazol-1-yl)phenol (20 g, 125 mmol) and NaOH (5.0 g, 125 mmol) in methanol (600 mL) was added 1-bromo-3-chloropropane (49 mL, 500 mmol). The reaction was stirred for 18 hours at 70° C. under nitrogen, concentrated, and partitioned between 1.0N NaOH/CH2Cl2. The organic phase was dried and concentrated to afford crude product which was purified by HPLC (5% CH3OH/CH2Cl2) to give 6.0 g (20%) of 1-[4-(3-chloropropoxy)phenyl]-1H-imidazole as a brown solid: mp 53°-55° C., 1H NMR (CDCl3): δ7.80 (brs, 1H), 7.30 (m, 3H), 7.20 (bs, 1H), 4.16 (t, J=6.0 Hz, 2H), 3.76 (t, J=6.0 Hz, 2H), 2.30 (m, 2H).
Reaction SMILES: [OH:1][CH2:2][C@H:3]([NH:8][C:9]([C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1C(OC(C)(C)C)=O)=[O:10])[C:4]([O:6][CH3:7])=[O:5].Cl>O1CCOCC1>[OH:1][CH2:2][C@H:3]([NH:8][C:9]([C@@H:11]1[CH2:15][CH2:14][CH2:13][NH:12]1)=[O:10])[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Product: COC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1
Temperature: 25 °C
Reaction time: 4 h
Yield: 82 %

Procedure:
(S)-Tert-butyl-2-((S)-3-hydroxy-1-methoxy-1-oxopropan-2-ylcarbamoyl)-pyrrolidine-1-carboxylate (3) (500 mg, 1.58 mmol) was dissolved in 1,4-dioxane (3 mL) and a HCl solution in dioxane (3.16 mL, 3.16 mmol) was added stirred at RT for 4 h. The volatiles were evaporated under reduced pressure to afford compound 4 (280 mg) as solid.
Reaction SMILES: [CH2:1]([C:9]1([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:21]2[CH:20]=[C:19](B(O)O)[CH:18]=[CH:17][C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[Br:33][C:34]1[CH:46]=[CH:45][C:44]2[C:43]3[C:38](=[CH:39][C:40](Br)=[CH:41][CH:42]=3)[C:37]([CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63])([CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])[C:36]=2[CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>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.C1(C)C=CC=CC=1>[Br:33][C:34]1[CH:35]=[C:36]2[C:44]([C:43]3[CH:42]=[CH:41][C:40]([C:19]4[CH:18]=[CH:17][C:16]5[C:15]6[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=6)[C:9]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:21]=5[CH:20]=4)=[CH:39][C:38]=3[C:37]2([CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH3:63])[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])=[CH:45][CH:46]=1
Reactant: CCCCCCCCC1(CCCCCCCC)c2cc(Br)ccc2-c2ccc(Br)cc21
Reactant: CCCCCCCCC1(CCCCCCCC)c2ccccc2-c2ccc(B(O)O)cc21
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: [Na+]
Solvent: Cc1ccccc1
Product: CCCCCCCCC1(CCCCCCCC)c2ccccc2-c2ccc(-c3ccc4c(c3)C(CCCCCCCC)(CCCCCCCC)c3cc(Br)ccc3-4)cc21
Temperature: 90 °C
Reaction time: 48 h
Yield: 63.8 %

Procedure:
A mixture of 9,9-bis(n-octyl)fluoren-2-yl-boronic acid (2a) (2.0 g, 4.60 mmol), 2,7-dibromo-9,9-bis(n-octyl)fluorene (3a) (4.0 g, 7.32 mmol), Pd(PPh3)4 (50 mg, 0.043 mmol), Na2CO3 (2.0 M aqueous solution, 12.0 mL, 24.0 mmol), and toluene (20 mL) is stirred at 90° C. for 2 days. After the mixture is cooled to room temperature, 200 mL of petroleum ether is added to the reaction mixture. The organic portion is separated and washed with brine before drying over anhydrous MgSO4. The solvent is evaporated off, and the solid residues are purified by column chromatography on silica gel with petroleum ether to afford 7-bromo-9,9,9′,9′-tetra-n-octyl-2,2′-bifluorene (4a) as a white solid (2.52 g, 66%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][C:7]1[CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][CH:8]=1.[ClH:20]>C(Cl)Cl.C(OCC)C>[ClH:20].[NH:10]1[CH2:9][CH:8]=[C:7]([CH2:6][C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[CH2:12][CH2:11]1
Reactant: CC(C)(C)OC(=O)N1CC=C(Cc2nccs2)CC1
Agent: Cl
Solvent: ClCCl
Solvent: CCOCC
Product: C1=C(Cc2nccs2)CCNC1
Temperature: 27.5 °C
Reaction time: 2 h

Procedure:
To a stirred solution of tert-butyl 4-(thiazol-2-ylmethyl)-5,6-dihydropyridine-1(2H)-carboxylate (F) (1.5 g, 5.36 mmol) in CH2Cl2 (20 mL) was added 2M HCl in diethyl ether (5 mL) dropwise at 0° C. and the reaction mixture was allowed to stir at 20-35° C. for 2 h. Then the reaction mixture was rotary evaporated under vacuum to get the desired compound as a brown liquid (1.6 g); 1H NMR (400 MHz, DMSO-d6) δ 9.23 (bs, 2H), 7.77 (d, J=2.5 Hz, 1H), 7.68 (d, J=3.2 Hz, 1H), 5.61 (s, 1H), 3.80 (s, 2H), 3.58-3.54 (m, 2H), 3.15-3.11 (m, 2H), 2.27-2.23 (m, 2H).
Reaction SMILES: [C:1]([NH:4]C1C=C(C=CC=1N=NC1C([N+]([O-])=O)=CC(Br)=CC=1Br)N(CC)CC)(=O)C.Br[C:30]1[CH:35]=[C:34]([N+:36]([O-:38])=[O:37])[CH:33]=[CH:32][C:31]=1[N:39]=[N:40][C:41]1[CH:59]=[CH:58][C:44]([N:45]([CH2:52][CH2:53][O:54][C:55](=[O:57])[CH3:56])[CH2:46][CH2:47][O:48][C:49](=[O:51])[CH3:50])=[CH:43][CH:42]=1>>[C:1]([C:30]1[CH:35]=[C:34]([N+:36]([O-:38])=[O:37])[CH:33]=[CH:32][C:31]=1[N:39]=[N:40][C:41]1[CH:59]=[CH:58][C:44]([N:45]([CH2:52][CH2:53][O:54][C:55](=[O:57])[CH3:56])[CH2:46][CH2:47][O:48][C:49](=[O:51])[CH3:50])=[CH:43][CH:42]=1)#[N:4]
Reactant: CCN(CC)c1ccc(N=Nc2c(Br)cc(Br)cc2[N+](=O)[O-])c(NC(C)=O)c1
Reactant: CC(=O)OCCN(CCOC(C)=O)c1ccc(N=Nc2ccc([N+](=O)[O-])cc2Br)cc1
Product: CC(=O)OCCN(CCOC(C)=O)c1ccc(N=Nc2ccc([N+](=O)[O-])cc2C#N)cc1
Reaction time: 7 h
Yield: 15.95 %

Procedure:
When the 3-acetylamino-4-(2',4'-di-bromo-6'-nitrophenylazo)-N,N-diethylaniline employed in Example 9 was replaced by 4-(2'-bromo-4'-nitrophenylazo)-N,N-di(β-acetoxyethyl)aniline (4.8 parts) reaction was effectively complete in 7 hours at 90° C. Isolation of the product by the method of Example 9 gave 4-(2'-cyano-4'-nitrophenylazo)-N,N-di(β-acetoxyethyl)aniline (Found: C, 57.4; H, 5.1; N, 16.1. C21H21N5O6 requires C, 57.4; H, 4.8; N, 15.95%).