Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[NH:27][C:28](=[O:30])[CH3:29])[C:18]2=[O:31])[CH2:13][CH:14]([OH:16])[CH3:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].C1C=CC(N=NC2C=CC(N)=NC=2N)=CC=1.Cl.[Cr](Cl)([O-])(=O)=O>C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[NH:27][C:28](=[O:30])[CH3:29])[C:18]2=[O:31])[CH2:13][C:14](=[O:16])[CH3:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]
Reactant: CCOc1cc(C(CC(C)O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC
Agent: O=[Cr](=O)([O-])Cl
Agent: Cl
Agent: Nc1ccc(N=Nc2ccccc2)c(N)n1
Solvent: ClCCl
Product: CCOc1cc(C(CC(C)=O)N2C(=O)c3cccc(NC(C)=O)c3C2=O)ccc1OC
Temperature: 25 °C
Reaction time: 4 h
Yield: 75.5 %

Procedure:
A mixture of N-{2-[1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindolin-4-yl}acetamide (1.2 g, 2.81 mmol), pyridium chlorochromate (1.21 g, 5.63 mmol) and celite (0.6 g) in methylene chloride (35 mL) was stirred at room temperature for 4 hours. The mixture was filtered through celite and the celite washed with methylene chloride. The filtrate was washed with water, brine, dried, and concentrated. The residue was purified by chromatography (silica gel, methylene chloride:ethyl acetate 9:1) to yield N-{2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindolin-4-yl}acetamide as a white solid (0.9 g, 76%); mp 128-129° C.; 1H NMR (CDCl3) δ 9.52 (s, 1H), 8.71 (d, J=8.4 Hz, 1H), 7.62 (t, J=7.5 Hz, 1H), 7.46 (d, J=7.2 Hz, 1H), 7.06-7.03 (m, 2H), 6.82 (d, J=8.9 Hz, 1H), 5.73-5.07 (dd, J=5.2 and 10.0 Hz, 1H), 4.11 (q, J=7.0 Hz, 2H), 4.04-3.93 (dd, J=10.0 and 18.0 Hz, 1H), 3.83 (s, 3H), 3.28-3.19 (dd, J=5.2 and 18.0 Hz, 1H), 2.26 (s, 3H), 2.18 (s, 3H), 1.46 (t, J=7.1 Hz, 3H); 13C NMR (CDCl3) δ 205.18, 170.62, 169.17, 167.10, 149.21, 148.40, 137.38, 135.81, 131.34, 131.24, 124.69, 120.02, 117.91, 115.30, 112.57, 111.37, 64.44, 55.93, 49.96, 44.82, 30.14, 24.93, 14.73; Anal. Calcd. For C23H24N2O6: C, 65.08; H, 5.70; N, 6.60. Found: C, 65.11; H, 5.64; N. 6.50.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[CH:5]([N:13]=[C:14]=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2].[NH2:17][C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:16])[CH:5]([NH:13][C:14]([NH:17][C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1)=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2]
Reactant: CCOC(=O)C(Cc1ccccc1)N=C=O
Reactant: N#Cc1ccc(N)cc1
Solvent: CN(C)C=O
Product: CCOC(=O)C(Cc1ccccc1)NC(=O)Nc1ccc(C#N)cc1
Reaction time: 168 h
Yield: 132.1 %

Procedure:
To a solution of 2-isocyanato-3-phenylpropionic acid ethyl ester (6 g, 27.37 mmol) in DMF (50 ml) was added a solution of 4-aminobenzonitrile (3.23 g, 27.37 mmol) in DMF (30 ml) at 3° C. during 20 min. Stirring was continued for 7 d at room temperature, and additional 2-isocyanato-3-phenylpropionic acid ethyl ester (2.86 g) was added successively. The solvent was removed and the residue dissolved in ethyl acetate (100 ml), washed with water (20 ml), saturated aqueous KHSO4/K2SO4 solution (1:1, 2×20 ml) and with saturated aqueous NaCl solution (4×90 ml). The organic phase was dried (MgSO4), filtered and evaporated to give 12.20 g of the title compound which was used without further purification. MS 338.3 (M+1)+
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7](Cl)[CH:8]=2)[N:3]=1.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][NH2:18]>>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][NH:18][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:18][CH2:17][C:16]3[CH:19]=[CH:20][CH:21]=[CH:22][C:15]=3[O:14][CH3:13])[CH:8]=2)[N:3]=1
Reactant: COc1ccccc1CN
Reactant: Clc1ccc2nc(Cl)ccc2c1
Product: COc1ccccc1CNc1ccc2nc(NCc3ccccc3OC)ccc2c1

Procedure:
The title compound, MS: m/e=400.4 (M+H+), was prepared in accordance with the general method of example 1 from 2,6-dichloroquinoline and 2-methoxybenzylamine.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.[C:20]12([CH2:30][NH2:31])[CH2:29][CH:24]3[CH2:25][CH:26]([CH2:28][CH:22]([CH2:23]3)[CH2:21]1)[CH2:27]2.C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C=O.O>[Cl:1][C:2]1[C:3]([N+:11]([O-:13])=[O:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:31][CH2:30][C:20]12[CH2:29][CH:24]3[CH2:23][CH:22]([CH2:28][CH:26]([CH2:25]3)[CH2:27]1)[CH2:21]2)=[O:7]
Reactant: O=C(O)c1cccc(Cl)c1[N+](=O)[O-]
Reactant: NCC12CC3CC(CC(C3)C1)C2
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: O=C(NCC12CC3CC(CC(C3)C1)C2)c1cccc(Cl)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.2 %

Procedure:
To a suspension of 3-chloro-2-nitrobenzoic acid (2.68 g) in dichloromethane (10 ml) at 0° C. was added oxalyl chloride (3 ml) and dimethylformamide (1 drop). The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour, then concentrated under reduced pressure to yield a solid. The solid was dissolved in dichloromethane (10 ml) and cooled to 0° C. A solution of 1-adamantanemethylamine (2.19 g) and N,N-diisopropylethylamine (11 ml) in dichloromethane (10 ml) was added portion-wise and the resulting solution allowed to stir at room temperature under a nitrogen atmosphere for 2 h. The reaction mixture was poured into water and the organic phase separated and washed with 2N hydrochloric acid, 10% aqueous sodium hydroxide and saturated brine. The organic phase was then dried over sodium sulfate, filtered and concentrated under reduced pressure and the resulting solid recrystallized from iso-propanol to afford the subtitle compound as a solid (3.52 g).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>ClCCl.CN(C1C=CN=CC=1)C>[CH3:22][S:23]([O:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1)(=[O:25])=[O:24]
Reactant: CC(C)(C)OC(=O)N1CCCC(O)C1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCCC(OS(C)(=O)=O)C1
Temperature: 0 °C
Reaction time: 8 h
Yield: 109.4 %

Procedure:
Tert-butyl 3-hydroxypiperidine-1-carboxylate (3.6 g, 18 mmol) was dissolved in dichloromethane (20 mL) and cooled to 0° C., triethylamine (4 mL) was added, followed by dropwise addition of methanesulfonyl chloride (2.28 g, 20 mmol) and DMAP (10 mg). The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was quenched with saturated NaHCO3, and extracted with dichloromethane. The organic layer was washed with H2O, dried and concentrated to give crude product (5.5 g).
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][CH2:6]/[C:7](=[CH:9]/[CH2:10][OH:11])/[CH3:8])[CH3:3].OC/C=C(/C)\CCC=C(C)C.O=O>O>[CH3:3][C:2](=[CH:4][CH2:5][CH2:6][C:7](=[CH:9][CH:10]=[O:11])[CH3:8])[CH3:1]
Reactant: CC(C)=CCC/C(C)=C/CO
Agent: CC(C)=CCC/C(C)=C\CO
Agent: O=O
Solvent: O
Product: CC(C)=CCCC(C)=CC=O

Procedure:
A 400 g portion of the catalyst precursor prepared in Example I was placed in about 57 cm. of a 79 cm. long (1.3 cm. diameter) reactor tube made from solid 316 type stainless steel. The catalyst precursor was reduced by passing a gaseous stream of geraniol and nerol (65% geraniol/35% nerol; 489 mg/min, 3.17 mmol/min), O2 (63 ml/min, 2.8 mmol/min), and steam (6.1 ml/min water) through the reactor tube at 375° C. (external sand bath temperature) to produce citral. This reaction was also performed using the catalyst precursor prepared as in Example II and the copper spheres prepared by analogy with the process described by British Patent Specification 1,381,587, respectively, in place of the catalyst precursor of Example I.
Reaction SMILES: P.[C:2]([O:6][C:7](=[O:18])[C:8]1[CH:13]=[CH:12][C:11](Br)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:5])([CH3:4])[CH3:3].[CH3:19][N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][OH:26]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(C)C=CC=CC=1>[CH3:19][N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][O:26][C:11]1[CH:12]=[CH:13][C:8]([C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:18])=[C:9]([N+:15]([O-:17])=[O:16])[CH:10]=1
Reactant: CN1CCC[C@H]1CO
Reactant: CC(C)(C)OC(=O)c1ccc(Br)cc1[N+](=O)[O-]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: P
Solvent: Cc1ccccc1
Product: CN1CCC[C@H]1COc1ccc(C(=O)OC(C)(C)C)c([N+](=O)[O-])c1
Temperature: 100 °C
Yield: 41.1 %

Procedure:
In a round bottomed three neck flask under argon atmosphere were added toluene (15 ml), CsCO3 (1.6 gr, 5 mmol), phosphine ligand 2-(di-tert-butylphosphino)-1,1′-binaphthyl (331 mg, 0.83 mmol) and Pd(dba)2 (380 mgr, 0.66 mmol). The mixture was degassed bubbling argon for five minutes. Then 4-bromo-2-nitrobenzoic acid tert butyl ester (1 gr, 3.31 mmol) and (S)-(−)-1-methyl-2-pyrrolidinemethanol (0.78 ml, 6.62 mmol) were added and the mixture was heated to 100° C. for 18 hr. The reaction was cooled to room temperature, quenched with 30 ml of water and extracted twice with 25 ml of AcOEt. The organic phases were collected, dried over Na2SO4 and the solvents evaporated to obtain a red oil which was subjected to chromatography purification on a Biotage SP1 automated system (90:10 DCM/MeOH (isocratic) to yield the pure title compound as a yellowish oil (460 mgr, 1.36 mmol, 41% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:30])[N:15]([CH2:17][C:18]4[C:19]([CH2:28][OH:29])=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:30])[N:15]([CH2:17][C:18]4[C:19]([CH:28]=[O:29])=[N:20][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:31]2[CH:32]=[CH:33][N:34]=[CH:35][CH:36]=2)=[CH:6][CH:7]=1
Reactant: O=c1n(Cc2ccc(C(F)(F)F)nc2CO)nc2c(-c3ccncc3)c(-c3ccc(Cl)cc3)ccn12
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: O=Cc1nc(C(F)(F)F)ccc1Cn1nc2c(-c3ccncc3)c(-c3ccc(Cl)cc3)ccn2c1=O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 98.1 %

Procedure:
The title compound was also prepared as follows: To a stirring solution of 7-(4-chlorophenyl)-2-((2-(hydroxymethyl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (162.4 mg, 0.32 mmol) in CH2Cl2 (5 mL) at room temperature was added 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one (Dess-Martin periodinane, 201 mg, 0.48 mmol) in one portion. The resulting mixture was stirred at room temperature for 10 min, then quenched by addition of water. The aqueous layer was extracted with CH2Cl2 (10 mL×2). The combined CH2Cl2 layers were washed with saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was purified using a silica gel cartridge (12 g) eluted with a gradient of ethyl acetate (30-100%) in hexanes to obtain 160 mg (99%) of the title compound as a yellow foam. HPLC/MS: retention time=2.78 min, [M+H]+=510.6.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH:22]4[CH2:24][CH2:23]4)=[CH:20][C:19]([CH:25]4[CH2:27][CH2:26]4)=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[C:4]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:3]=1.[CH3:32][C@@H:33]1[O:37][C:36](=[O:38])[NH:35][CH2:34]1>>[CH:22]1([C:21]2[C:16]([N:13]3[CH2:14][CH2:15][N:10]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([N:35]5[CH2:34][C@H:33]([CH3:32])[O:37][C:36]5=[O:38])=[CH:3][C:4]=4[S:28]([CH3:31])(=[O:30])=[O:29])=[O:9])[CH2:11][CH2:12]3)=[N:17][CH:18]=[C:19]([CH:25]3[CH2:27][CH2:26]3)[CH:20]=2)[CH2:24][CH2:23]1
Reactant: C[C@H]1CNC(=O)O1
Reactant: CS(=O)(=O)c1cc(Br)ccc1C(=O)N1CCN(c2ncc(C3CC3)cc2C2CC2)CC1
Product: C[C@H]1CN(c2ccc(C(=O)N3CCN(c4ncc(C5CC5)cc4C4CC4)CC3)c(S(C)(=O)=O)c2)C(=O)O1
Yield: 62.1 %

Procedure:
By reaction and treatment in the same manner as in Example 111 and using (4-bromo-2-methanesulfonylphenyl)[4-(3,5-dicyclopropylpyridin-2-yl)piperazin-1-yl]methanone (400 mg) described in Preparation Example 89 and (S)-5-methyloxazolidin-2-one (80.2 mg) described in Preparation Example 42, the title compound (258.4 mg) was obtained.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:11][O:12][C:13]([C:15]1[O:16][C:17]([CH2:20]Cl)=[CH:18][CH:19]=1)=[O:14]>CN(C)C=O>[CH3:11][O:12][C:13]([C:15]1[O:16][C:17]([CH2:20][O:8][C:5]2[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=2)=[CH:18][CH:19]=1)=[O:14]
Reactant: Oc1ccc(I)cc1
Reactant: COC(=O)c1ccc(CCl)o1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(COc2ccc(I)cc2)o1
Temperature: 5 °C
Reaction time: 1 h
Yield: 28 %

Procedure:
A solution of 4-iodophenol (10.08 g, 45.8 mmol) in N,N-dimethylformamide (30 mL) was added to a ice-bath cooled suspension of sodium hydride (60%; 1.65 g, 41.2 mmol) in N,N-dimethylformamide (30 mL). The ice bath was removed and the mixtrue was stirred for 1 h. The mixture was cooled again to ˜5° C. and a solution of 5-(chloro-methyl)-furan-2-carboxylic acid methyl ester (4.00 g, 22.9 mmol) in N,N-dimethylformamide (60 mL) was added. The reaction mixture was stirred overnight at room temperature, then the solvents were evaporated under reduced pressure and water was added. The mixture was extracted three times with ethyl acetate and the combined organic layers were washed twice with 1 M NaOH, and once each with water and brine. The organic solution was dried (magnesium sulfate), filtered, evaporated, and purified using a Biotage 65 L purification system, eluting with 3% methylene chloride/toluene to give 5-(4-iodo-phenoxymethyl)-furan-2-carboxylic acid methyl ester (2.3 g, 28%) as a white solid, along with some mixed fractions.
Reaction SMILES: C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[CH2:19]([N:22]1[CH:26]=[C:25]([C:27]2[CH:28]=[C:29]([CH:38]=[CH:39][CH:40]=2)[CH2:30][CH2:31][O:32][CH2:33][CH2:34][C:35]([OH:37])=O)[CH:24]=[N:23]1)[CH2:20][CH3:21].[CH3:41][O:42][CH:43]([O:51][CH3:52])[CH2:44][NH:45][CH:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1.C(=O)([O-])O.[Na+]>C1COCC1.C(#N)C.C(N(CC)CC)C>[CH:46]1([N:45]([CH2:44][CH:43]([O:51][CH3:52])[O:42][CH3:41])[C:35](=[O:37])[CH2:34][CH2:33][O:32][CH2:31][CH2:30][C:29]2[CH:38]=[CH:39][CH:40]=[C:27]([C:25]3[CH:24]=[N:23][N:22]([CH2:19][CH2:20][CH3:21])[CH:26]=3)[CH:28]=2)[CH2:47][CH2:48][CH2:49][CH2:50]1
Reactant: CCCn1cc(-c2cccc(CCOCCC(=O)O)c2)cn1
Reactant: COC(CNC1CCCC1)OC
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCCn1cc(-c2cccc(CCOCCC(=O)N(CC(OC)OC)C3CCCC3)c2)cn1
Temperature: 22 °C
Reaction time: 0.5 h

Procedure:
A solution of T3P (0.637 mL, 1.57M) dissolved in THF was added to a stirred solution of 3-(3-(1-propyl-1H-pyrazol-4-yl)phenethoxy)propanoic acid [Example 18, Step ii)] (151 mg), triethylamine (0.906 mL) and N-(2,2-dimethoxyethyl)cyclopentanamine [Preparation 9] (106 mg) in acetonitrile (2 mL) at 22° C. under air. The resulting solution was stirred at 22° C. for 30 min. The reaction mixture was neutralised with saturated sodium hydrogen carbonate and extracted with DCM. The organic was filtered through a phase separator cartridge and evaporated to afford crude product. The crude product was purified by flash silica chromatography using elution gradient 0 to 100% ethyl acetate in isohexane to the subtitled compound (150 mg) as an oil. MS [M+H-MeOH]+=426 (MultiMode+) 1H NMR (300 MHz, CD3OD) δ 8.00 (s, 1H), 7.83 (s, 1H), 7.43 (s, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.26 (t, J=7.6 Hz, 1H), 7.09 (d, J=7.5 Hz, 1H), 4.60 and 4.41 (2×t, J=5.2 Hz, 1H), 4.31-4.18 (m, 1H), 4.14 (t, J=7.0 Hz, 2H), 3.80-3.67 (m, 4H), 3.39 and 3.26 (2×d, J=5.3 Hz, 2H), 3.38 (s, 3H), 3.36 (s, 3H), 2.88 (t, J=6.6 Hz, 2H), 2.69 (t, J=6.2 Hz, 2H), 1.92 (sextet, J=7.2 Hz, 2H), 1.85-1.47 (m, 8H), 0.95 (t, J=7.4 Hz, 3H), a ˜1:1 mixture of rotamers is observed.
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:19]=[CH:18][C:10]2[S:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:9]=2[CH:8]=1.B(OCCCC)(OCCCC)[O:21]CCCC.OO.Cl>CCOCC>[OH:21][C:7]1[CH:19]=[CH:18][C:10]2[S:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:9]=2[CH:8]=1
Reactant: CCCCOB(OCCCC)OCCCC
Reactant: Brc1ccc2sc3ccccc3c2c1
Agent: Cl
Agent: OO
Agent: [Li]CCCC
Solvent: CCOCC
Product: Oc1ccc2sc3ccccc3c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 85.9 %

Procedure:
Butyl lithium (0.05 mole) in ether was added to 2-bromodibenzothiophene (13.15 g, 0.05 mole) in 150 ml dry ether at 0°C. The mixture was then cooled to -70° and freshly distilled tributyl borate (11.5 g, 0.05 mole) dissolved in 50 ml ether was added. The reaction mixture was stirred for 2 hours, and was then allowed to warm up to room temperature. Perhydrol (10 ml) was added and the mixture was refluxed for 1.5 hours. Hydrochloric acid was added and the organic phase was separated. The ether was washed with 10 % ferrous ammonium sulphate solution and then extracted with sodium hydroxide solution. The alkaline aqueous solution was acidified and extracted with ether, which after evaporation gave 8.6 g (86 %) of the desired product. Recrystallization from ligroin gave white crystals with m.p. 152°-155°.
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]([C:5]1[C:16]([CH2:17][CH2:18][CH:19](O)C2C=CC=CC=2)=[C:15]([OH:27])[C:8]2[N:9]=[C:10]([CH2:13][CH3:14])[N:11]([CH3:12])[C:7]=2[CH:6]=1)=[O:4].[OH-].[Na+]>P(=O)(O)(O)O>[CH3:28][N:2]([CH3:1])[C:3]([C:5]1[C:16]2[CH2:17][CH2:18][CH2:19][O:27][C:15]=2[C:8]2[N:9]=[C:10]([CH2:13][CH3:14])[N:11]([CH3:12])[C:7]=2[C:6]=1[C:5]1[CH:16]=[CH:15][CH:8]=[CH:7][CH:6]=1)=[O:4]
Reactant: CCc1nc2c(O)c(CCC(O)c3ccccc3)c(C(=O)N(C)C)cc2n1C
Agent: O=P(O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: CCc1nc2c3c(c(C(=O)N(C)C)c(-c4ccccc4)c2n1C)CCCO3
Temperature: 80 °C
Reaction time: 2 h
Yield: 113.3 %

Procedure:
A suspension of 1.3 g (3.4 mmol) 2-ethyl-7-hydroxy-6-(3-hydroxy-3-phenyl-propyl)-3-methyl-3H-benzoimidazole-5-carboxylic acid dimethylamide in 13 ml 85% orthophosphoric acid was heated to 80° C. After 2 h stirring, the reaction was cooled to room temperature, neutralized with 6M sodium hydroxide (65 ml) and extracted with dichloromethane (4×150 ml). The organic layers were dried over magnesium sulphate and concentrated in vacuo to afford 0.7 g (57%) of the title compound as a white solid. m.p. 195°-197° C.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)[CH:5]=[CH:6][CH:7]=1.Cl.[CH3:33][C:34]1[CH:39]=[CH:38][C:37]([NH:40]N)=[CH:36][CH:35]=1>>[I:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:40][C:37]3[C:38]([C:9]=2[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=4)[CH2:15][CH2:14]2)=[CH:39][C:34]([CH3:33])=[CH:35][CH:36]=3)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3cccc(I)c3)CC2)c1
Reactant: Cc1ccc(NN)cc1
Agent: Cl
Product: Cc1ccc2[nH]c(-c3cccc(I)c3)c(CCCN3CCC(c4cccc(NC(=O)C(C)C)c4)CC3)c2c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(3-iodophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 4-methylphenylhydrazine hydrochloride: ESMS m/e: 620.2 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]=[N:10][C:11]2[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)#[N:2].[OH-].[CH2:23]([N+:27]([CH2:36][CH2:37][CH2:38][CH3:39])([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH3:26]>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]=[N:10][C:11]2[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[CH:7][CH:8]=1)#[N:2].[CH2:36]([N+:27]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:32][CH2:33][CH2:34][CH3:35])[CH2:37][CH2:38][CH3:39]
Reactant: N#Cc1ccc(N=Nc2ccc(OCC(=O)O)cc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [OH-]
Solvent: ClCCl
Product: N#Cc1ccc(N=Nc2ccc(OCC(=O)[O-])cc2)cc1
Temperature: 30 °C

Procedure:
1.06 g (0.004 mol) of 2-[4-(4-cyanopbenylazo)phenoxy]-ethanoic acid was transferred to a 50 mL one-neck round flask fitted with a magnetic stirring bar and 10.4 mL of a 20% aqueous solution of tetrabutylammonium hydroxide (Merck, zur Synthese) was added and the mixture heated while stirring on an oilbath until a solution was formed The solution was cooled to approx. 30° C., 3.5 mL of methylene chloride was added and vigorously stirred. The liquids were transferred to a separating funnel with a pipette and allowed to separate. The dark red, lower methylene chloride solution was drained into a 25 mL beaker. The remaining aqueous phase was washed with additional 1.5 mL of methylene chloride which was also added the beaker. The combined methylene chloride solutions of tetrabutylammonium 2-[4-(4-cyanophenylazo)phenoxy]-ethanoate were dried with Na2SO4 for ½ h and filtered. The filtercake was further washed with 1 mL of methylene chloride and the combined tetrabutylammonium 2-[4-(4-cyanophenyl-azo)phenoxy]-ethanoate solution was diluted to 8 mL corresponding to an 0.5 M solution.
Reaction SMILES: C(N(CC)CC)C.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([O:21][CH2:22][C:23](=O)[NH:24][NH:25][C:26]([C:28]2[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=2)=[O:27])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]>C(Cl)Cl>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([O:21][CH2:22][C:23]2[O:27][C:26]([C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)=[N:25][N:24]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:9])([CH3:11])[CH3:10]
Reactant: CC(C)(C)OC(=O)N1CCC(OCC(=O)NNC(=O)c2ccncc2)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(OCc2nnc(-c3ccncc3)o2)CC1
Reaction time: 18 h

Procedure:
Triethylamine (149 μl, 1.06 mmol was added to stirred solution of 4-{2-oxo-2-[N′-(pyridine-4-carbonyl)hydrazino]ethoxy}piperidine-1-carboxylic acid tert-butyl ester (Preparation 16, 200 mg, 0.53 mmol) and 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (147 mg, 0.53 mmol) in CH2Cl2 (10 ml). After 18 h at rt, the solvent was reduced to a small volume and this mixture purified by flash chromatography (EtOAc), affording the title compound: RT=3.42 min; m/z (ES+)=361.1 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1([CH3:24])[CH2:11][C:10]([CH3:13])([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:14]#[C:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][OH:23])=[CH:18][N:17]=3)[CH:8]=2)[O:3]1.[C:25](O)(=[O:27])[CH3:26].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:1][C:2]1([CH3:24])[CH2:11][C:10]([CH3:12])([CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:14]#[C:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][O:23][C:25](=[O:27])[CH3:26])=[CH:18][N:17]=3)[CH:8]=2)[O:3]1
Reactant: CC(=O)O
Reactant: CC1(C)CC(C)(C)c2cc(C#Cc3ccc(CO)cn3)ccc2O1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC(=O)OCc1ccc(C#Cc2ccc3c(c2)C(C)(C)CC(C)(C)O3)nc1

Procedure:
A solution of 3.09 g (10 mmol) of 2,2,4,4-tetramethyl-6-[2-(5-hydroxymethylpyrid-2-yl)ethynyl]chroman (Compound 50) 600 mg (10 mmol) of glacial acetic acid, 2.06 g (10 mmol) of dicyclohexylcarbodiimide and 460 mg (3.765 mmol) of 4-dimethylaminopyridine in 150 ml methylene chloride is stirred at room temperature for 48 hours. The reaction mixture is then filtered and the residue washed with 50 ml of methlene chloride. The filtrate is then concentrated in vacuo and the residue is purified by chromatography followed by recrystallization to give the title compound.