Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].[OH2:4]>>[OH:3][CH2:1][C@@H:2]([C@H:1]([C@@H:2]([C@@H:1]([CH2:2][OH:4])[OH:3])[OH:4])[OH:3])[OH:4]
Reactant: CCO
Reactant: O
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO

Procedure:
A solution is formed of the ethanol, water and sorbitol ingredients. The Pluronic F-108 is added, followed by sodium bicarbonate and zinc oxide andthe other ingredients in the listed order with high speed stirring.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][CH:7]([CH3:19])[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(Cl)(Cl)Cl.CN(C=O)C>[Cl:3][CH2:6][CH:7]([CH3:19])[CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(CO)CCCCOc1ccccc1
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Product: CC(CCl)CCCCOc1ccccc1

Procedure:
A solution of 60 g of thionyl chloride in 50 ml of CHCl3 was added dropwise to 100 g of 1-Hydroxy-2-methyl-6-phenoxy-hexane in 200 ml of CHCl3 and 0.5 ml of DMF. The solution was refluxed until the development of the gas was finished and then poured onto ice. The aqueous phase was extracted twice with CHCl3 and the combined organic phases were washed with water and finally with a saturated NaHCO3 -solution, dried with MgSO4, evaporated and the residue was distilled off.
Reaction SMILES: [NH2:1][C:2]1[N:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].Cl[CH2:13][CH:14]=O>C(O)C.O.N>[N:1]1[CH:13]=[CH:14][N:11]2[CH:10]=[CH:9][CH:8]=[C:3]([C:4]([O:6][CH3:7])=[O:5])[C:2]=12
Reactant: O=CCCl
Reactant: COC(=O)c1cccnc1N
Agent: N
Solvent: CCO
Solvent: O
Product: COC(=O)c1cccn2ccnc12

Procedure:
A mixture of methyl 2-aminonicotinate (WO 89/01488 pg33, prep 17) (1 g, 6.56 mmol), and chloroacetaldehyde (1.05 mL, 6.56 mmol) in ethanol (5 mL) was heated under reflux for 18 hours. The cooled mixture was diluted with water (10 mL), 0.88 ammonia (1 mL) added and the solution concentrated in vacuo. The residue was dissolved in methanol and the dark solution treated with charcoal, the mixture filtered and the filtrate concentrated in vacuo. The residue was purified by column chromatography on silica gel using dichloromethane:methanol:0.88 ammonia (97:2.5:0.5) as eluant, and the product triturated with ether, to afford the title compound, 768 mg.
Reaction SMILES: [I-].[K+].[SH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:14])[C:9](=[O:15])[CH2:8][CH2:7]2.Cl[C:17]1[S:18][C:19]([C:22]2([O:30][CH3:31])[CH2:27][CH2:26][O:25][C:24]([CH3:29])([CH3:28])[CH2:23]2)=[CH:20][N:21]=1>>[CH3:31][O:30][C:22]1([C:19]2[S:18][C:17]([S:3][C:4]3[CH:5]=[C:6]4[C:11](=[CH:12][CH:13]=3)[N:10]([CH3:14])[C:9](=[O:15])[CH2:8][CH2:7]4)=[N:21][CH:20]=2)[CH2:27][CH2:26][O:25][C:24]([CH3:29])([CH3:28])[CH2:23]1
Reactant: CN1C(=O)CCc2cc(S)ccc21
Reactant: COC1(c2cnc(Cl)s2)CCOC(C)(C)C1
Agent: [I-]
Agent: [K+]
Product: COC1(c2cnc(Sc3ccc4c(c3)CCC(=O)N4C)s2)CCOC(C)(C)C1
Yield: 80 %

Procedure:
Using an analogous procedure to that described in Example 1 except that a catalytic amount (0.01 g) of potassium iodide was added, 6-mercapto-1-methyl-1,2,3,4-tetrahydroquinolin-2-one was reacted with 4-(2-chlorothiazol-5-yl)-4-methoxy-2,2-dimethyltetrahydropyran to give 4-methoxy-2,2-dimethyl-4-[2-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-ylthio)thiazol-5-yl]tetrahydropyran in 80% yield as a foam;
Reaction SMILES: [CH3:1][O:2][N:3]=[C:4]1[C:12]2[CH:11]=[CH:10][N:9]=N[C:7]=2[O:6][CH2:5]1.[CH:13]1([C:16]2N=CC=C3C(=O)COC=23)[CH2:15][CH2:14]1>>[CH3:1][O:2][N:3]=[C:4]1[C:12]2[C:7](=[C:16]([CH:13]3[CH2:15][CH2:14]3)[N:9]=[CH:10][CH:11]=2)[O:6][CH2:5]1
Reactant: O=C1COc2c1ccnc2C1CC1
Reactant: CON=C1COc2nnccc21
Product: CON=C1COc2c1ccnc2C1CC1

Procedure:
This compound was prepared using a method analogous to that of furo[2,3-c]pyridazin-5(6H)-one O-methyl oxime (A.2.3.3), 7-cyclopropylfuro[2,3-c]pyridin-3(2H)-one replacing furo[2,3-c]pyridazin-5(6H)-one. Purification by CC (KP-SIL™ from Biotage) using Hept/EtOAc (9/1) gives the desired product as brown oil;
Reaction SMILES: Cl.[OH:2][C@H:3]1[CH2:7][NH:6][CH2:5][C@@H:4]1[NH:8][C:9]([C:11]1[S:12][C:13]([Cl:16])=[CH:14][CH:15]=1)=[O:10].BrC([C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]2=[O:34])=[CH:24][C:23]=1[F:35])C(N)=O>CN(C=O)C>[F:35][C:23]1[CH:24]=[C:25]([N:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]2=[O:34])[CH:26]=[CH:27][C:22]=1[NH:8][C:9]([CH2:11][N:6]1[CH2:7][C@H:3]([OH:2])[C@@H:4]([NH:8][C:9]([C:11]2[S:12][C:13]([Cl:16])=[CH:14][CH:15]=2)=[O:10])[CH2:5]1)=[O:10]
Reactant: NC(=O)C(Br)c1ccc(-n2ccccc2=O)cc1F
Reactant: O=C(N[C@H]1CNC[C@@H]1O)c1ccc(Cl)s1
Agent: Cl
Solvent: CN(C)C=O
Product: O=C(CN1C[C@H](NC(=O)c2ccc(Cl)s2)[C@@H](O)C1)Nc1ccc(-n2ccccc2=O)cc1F

Procedure:
22.6 Using general procedure A with DMF as solvent 5-chloro-thiophene-2-carboxylic acid ((3S,4S)-4-hydroxy-pyrrolidin-3-yl)-amide hydrochloride was reacted with 2-bromo-[2-fluoro-4-(2-oxo-pyridin-1-yl)-phenyl]-acetamide to give 5-chloro-thiophene-2-carboxylic acid ((3S,4S)-1-{[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-methyl}-4-hydroxy-pyrrolidin-3-yl)-amide. Light-yellow solid. MS 491.3 ([M+H]+)
Reaction SMILES: [H-].[Na+].[OH:3][C@@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH3:23]I.O>CN(C=O)C>[CH3:23][O:3][C@@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]1[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](O)[C@H](c2ccccc2)C1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CO[C@@H]1CCN(C(=O)OC(C)(C)C)C[C@H]1c1ccccc1
Temperature: 22 °C
Reaction time: 0.5 h
Yield: 101.8 %

Procedure:
Add sodium hydride (2.19 g, 54.75 mmol) in one portion to a solution of (−)trans-tert-butyl 4-hydroxy-3-phenyl-piperidine-1-carboxylate (11.8 g, 42.12 mmol) in DMF (168.5 mL) at 0° C. under a nitrogen atmosphere. Stir the mixture for 30 min and then add methyl iodide (3.15 mL, 50.54 mmol) dropwise. Stir the mixture at 0° C. for 1 minute and warm to 22° C. for 1 hour. Add additional sodium hydride (303 mg, 12.6 mmol), stir for 15 min, and then add methyl iodide (0.52 mL, 8.4 mmol) slowly. Stir the mixture at 22° C. for 1 hour, cool to 0° C. for 1 hour and add water (118 mL) carefully. Filter the resulting suspension, rinse the solid with water and dry the solid in the vacuum oven (45° C., 60 mbar) to obtain the title compound as a white solid (12.5 g, 99%). MS (m/z): 192 (M-Boc+1), 236 (M-tBu+1).
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:22]1[N:31]=[CH:30][C:29]2[C:24](=[CH:25][C:26]([O:34][CH3:35])=[C:27]([O:32][CH3:33])[CH:28]=2)[N:23]=1>C(O)CCCC>[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([C:22]3[N:31]=[CH:30][C:29]4[C:24](=[CH:25][C:26]([O:34][CH3:35])=[C:27]([O:32][CH3:33])[CH:28]=4)[N:23]=3)[CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1cc2cnc(Cl)nc2cc1OC
Reactant: CC(C)(C)OC(=O)c1ccc(NC2CCNCC2)cc1
Solvent: CCCCCO
Product: COc1cc2cnc(N3CCC(Nc4ccc(C(=O)OC(C)(C)C)cc4)CC3)nc2cc1OC
Temperature: 120 °C
Reaction time: 12 h
Yield: 20.8 %

Procedure:
4-(Piperidin-4-ylamino)benzoic acid tert-butyl ester (49) (0.15 g, 0.54 mmol), was added to a solution of 2-chloro-6,7-dimethoxy-quinazoline (0.07 g, 0.31 mmol) in n-pentanol (5 mL) at 25° C. The mixture was stirred at 120° C. for 12 h. The reaction mixture was then cooled to room temperature and concentrated to a brown solid residue. Purification of the residue by flash column chromatography (gradient elution 30 to 40% EtOAc/hexanes) provided the title compound (0.03 g, 18%): TLC (Rf =0.50; 50% EtOAc/hexanes); 1H NMR (DMSO) δ 8.93 (s, 1H), 7.62 (d, 2H, J=8.7), 7.20 (s, 1H), 6.91 (s, 1H), 6.61 (d, 2H, J=8.8), 6.37 (d, 1H, J=7.9), 4.67 (d, 2H, J=13.2), 3.89 (s, 3H), 3.82 (s, 3H), 3.65 (m, 1H), 3.16 (t, 2H, J=11.5), 1.97 (d, 2H, J=10.4), 1.48 (s, 9H), 1.36 (m, 2H); 13C NMR (DMSO) δ 165.3, 158.6, 158.4, 156.1, 151.5, 149.3, 146.5, 130.9, 117.5, 113.9, 111.1, 105.4, 104.4, 78.9, 55.8, 55.6, 48.9, 42.5, 31.2, 28.0; HRMS (FAB) m/z 465.2503 (M+H)+ (C26H32N4O4 requires 465.2494); Anal. (C26H32N4O4 ·1/4HCl·1/4H2O) C, H, N.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].C1OCCOCCOCCOCCOCCOC1.[CH2:35]([O:37][CH:38]([O:45][CH2:46][CH3:47])[C:39]#[C:40][C:41]([O:43][CH3:44])=[O:42])[CH3:36]>C1COCC1.O>[CH2:46]([O:45][CH:38]([O:37][CH2:35][CH3:36])/[C:39](/[O:14][C:11]1[CH:10]=[CH:9][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:13][CH:12]=1)=[CH:40]/[C:41]([O:43][CH3:44])=[O:42])[CH3:47]
Reactant: CCOC(C#CC(=O)OC)OCC
Reactant: Oc1ccc(Oc2ccccc2)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(OCC)/C(=C/C(=O)OC)Oc1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 54.1 %

Procedure:
To a solution of 2.79 g (15 mmol) of 4-phenoxyphenol in 40 mL of THF was added 1.14 g (20 mmol) of powdered KOH and 5.28 g (20 mmol) of 18-crown-6. The solution was heated to 50° C. for 15 minutes, whereupon 3.72 g (20 mmol) of methyl 4,4-diethoxy-2-butynoate was added. The mixture was stirred for 30 minutes, then allowed to cool to room temperature. The solution was then poured into water, and extracted 3 times with 40 mL of ethyl acetate. The organic layers were combined, dried (MgSO4) and concentrated. The crude oil was subjected to column chromatography on SiO2. Elution with 20% ethyl acetate-hexane yielded 3.02 g (55%) of an oil, used in the next step without further purification.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:11]([NH2:15])([CH3:14])([CH3:13])[CH3:12]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[N:15][C:11]([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)N
Reactant: O=Cc1ccc(F)cc1F
Solvent: Cc1ccccc1
Product: CC(C)(C)N=Cc1ccc(F)cc1F

Procedure:
To a solution of 2,4-difluorobenzaldehyde (431.6 mg, 3.04 mmol) in toluene (5 ml) was added t-butylamine (0.63 ml, 6.00 mmol) and stirred under reflux using a Dean-Stark trap to remove water for 1 hour. Then t-butylamine (0.63 ml, 6.00 mmol) was added to the mixture and stirred for 5 hours. The solvent was evaporated to give the title compound.
Reaction SMILES: [C:1]([O:10]C)(=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4].[C:12]([C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1)#[N:13].C(N(CC)CC)C>C1(C)C=CC=CC=1>[N:17]1[CH:18]=[CH:19][C:14]([C:12]2[S:4][C:3]3[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=3[C:1](=[O:10])[N:13]=2)=[CH:15][CH:16]=1
Reactant: COC(=O)c1ccccc1S
Reactant: N#Cc1ccncc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: O=c1nc(-c2ccncc2)sc2ccccc12
Yield: 30.7 %

Procedure:
Methyl thiosalicylate (2.0 g, 11.9 mM) and 4-cyanopyridine (1.2 g, 11.5 mM) were dissolved in toluene (5 ml), and then triethylamine (2 ml) was added thereto. After heating the mixture under reflux for 22 hours, the same processes as described in Reference Example 1 were performed to give the title compound as crystals (850 mg, 30.7%).
Reaction SMILES: [CH3:1][C:2]([C:9](=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:16])([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].CO>O>[Cl:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[CH:9]([OH:17])[C:2]([CH3:8])([CH3:1])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCOC(=O)C(C)(C)C(=O)c1ccccc1Cl
Solvent: CO
Solvent: O
Product: CCOC(=O)C(C)(C)C(O)c1ccccc1Cl
Temperature: 70 °C
Reaction time: 24 h
Yield: 81.8 %

Procedure:
tBuBisP*-RuBr2 (5 mg) was placed in a pressurized hydrogenation reactor equipped with a stirrer chip, and after deaeration, substituted with argon. Thereto was poured a mixture of deaerated ethyl 2,2-dimethyl(2-chlorobenzoyl)acetate (515 mg) (2.0 mmol), methanol (4 ml) and water (0.4 ml). The mixture was stirred under a hydrogen pressure (6 atm) at 70° C. for 24 h. According to the high performance liquid chromatography analysis of the mixture after completion of the reaction, the yield was 97% and enantioselectivity was 90% ee. After the analysis, the reaction mixture was concentrated to dryness and purified by column chromatography (hexane:ethyl acetate=3:1, silica gel: 50 g) to give the title compound (420 mg, 81.8%) as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[O:3][CH:4]([CH:8]([CH3:10])[CH3:9])[C:5](=[O:7])[N:6]=1.[CH2:11]([CH:18]1[CH2:23][CH2:22]N[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([CH:18]1[CH2:23][CH2:22][N:1]([C:2]2[O:3][CH:4]([CH:8]([CH3:10])[CH3:9])[C:5](=[O:7])[N:6]=2)[CH2:20][CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CC(C)C1OC(N)=NC1=O
Reactant: c1ccc(CC2CCNCC2)cc1
Product: CC(C)C1OC(N2CCC(Cc3ccccc3)CC2)=NC1=O

Procedure:
Synthesis was performed from 2-amino-5-isopropyl-1,3-oxazol-4(5H)-one and 4-benzylpiperidine according to Method G+H.
Reaction SMILES: [C:1]([C:5]1[C:15]([F:16])=[CH:14][C:8]([O:9][CH2:10][C:11]([OH:13])=O)=[CH:7][C:6]=1[F:17])([CH3:4])([CH3:3])[CH3:2].[Cl-].ClC1N(C)CC[NH+]1C.Cl.[NH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([NH:37][S:38]([CH3:41])(=[O:40])=[O:39])=[CH:33][CH:32]=1)[CH3:30]>C(N(CC)CC)C>[C:1]([C:5]1[C:6]([F:17])=[CH:7][C:8]([O:9][CH2:10][C:11]([NH:28][C@@H:29]([C:31]2[CH:32]=[CH:33][C:34]([NH:37][S:38]([CH3:41])(=[O:40])=[O:39])=[CH:35][CH:36]=2)[CH3:30])=[O:13])=[CH:14][C:15]=1[F:16])([CH3:2])([CH3:3])[CH3:4]
Reactant: C[C@@H](N)c1ccc(NS(C)(=O)=O)cc1
Reactant: CC(C)(C)c1c(F)cc(OCC(=O)O)cc1F
Agent: CN1CC[NH+](C)C1Cl
Agent: Cl
Agent: [Cl-]
Solvent: CCN(CC)CC
Product: C[C@@H](NC(=O)COc1cc(F)c(C(C)(C)C)c(F)c1)c1ccc(NS(C)(=O)=O)cc1
Yield: 63.2 %

Procedure:
((4-tert-Butyl-3,5-difluorophenoxy)acetic acid (147 mg, 0.60 mmol), 2-chloro-1,3-dimethylimidazolinium chloride (CDI) (102 mg, 0.63 mmol), triethylamine (0.5 ml) and N-{4-[(1R)-1-aminoethyl]phenyl}methanesulfonamide hydrochloride (150 mg, 0.60 mmol) were mixed by the same procedure as described in Example 1(e) to give 167 mg (63%) of the title compound as a white solid.
Reaction SMILES: [CH3:1][C:2]([Si:5]([CH3:25])([CH3:24])[O:6][C@@H:7]1[C@@H:11]([CH2:12][Si:13]([CH3:21])([CH3:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([CH2:22][OH:23])=[CH:9][CH2:8]1)([CH3:4])[CH3:3].C(O[O-])(=O)C1C(=CC=CC=1)C([O-])=[O:30].[Mg+2]>CO.C(OCC)(=O)C>[CH3:4][C:2]([Si:5]([CH3:25])([CH3:24])[O:6][C@H:7]1[CH2:8][C@@H:9]2[C@@:10]([CH2:22][OH:23])([O:30]2)[C@@H:11]1[CH2:12][Si:13]([CH3:21])([CH3:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)([CH3:1])[CH3:3]
Reactant: O=C([O-])c1ccccc1C(=O)O[O-]
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1CC=C(CO)[C@@H]1C[Si](C)(C)c1ccccc1
Agent: [Mg+2]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)O[C@H]1C[C@H]2O[C@@]2(CO)[C@@H]1C[Si](C)(C)c1ccccc1
Temperature: 0 °C
Reaction time: 4 h
Yield: 92.3 %

Procedure:
To a cooled (0° C.), stirred solution of 44 (14 g, 37.23 mmol) in MeOH (50 mL) was added magnesium monoperoxyphthalate (MPPA, 80% pure, 27.62 g, 44.68 mmol) in six portions over a period of 1 hour, keeping the temperature <0° C. The reaction mixture was stirred at the same temperature for 4 hours to complete the reaction. The reaction mixture was diluted with ethyl acetate (300 mL) and washed with saturated sodium bisulfite (200 mL), sodium hydroxide (0.5 N, 2×150 mL), brine (150 mL) and dried over magnesium sulfate. The organic layer was concentrated in vacuo to dryness to give the crude title compound (13.5 g, 92%)
Reaction SMILES: [OH:1][C@H:2]1[C@@H:27]2[O:28][C@@H:26]2[C@@:25]2([CH3:29])[C:4](=[CH:5][CH:6]=[C:7]3[C@@H:24]2[CH2:23][CH2:22][C@@:21]2([CH3:30])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:20])[CH2:13][CH2:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[CH2:3]1.[CH2:31]([OH:35])[CH2:32][CH2:33][OH:34].CC(C)([O-])C.[K+].C1OCCOC2C(=CC=CC=2)OCCOCCOC2C(=CC=CC=2)OC1>O>[OH:34][CH2:33][CH2:32][CH2:31][O:35][C@H:27]1[C@H:26]([OH:28])[C@@:25]2([CH3:29])[C:4](=[CH:5][CH:6]=[C:7]3[C@@H:24]2[CH2:23][CH2:22][C@@:21]2([CH3:30])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:20])[CH2:13][CH2:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[CH2:3][C@H:2]1[OH:1]
Reactant: C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)[C@@H]5O[C@@H]5[C@]4(C)[C@H]3CC[C@]12C
Reactant: OCCCO
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: c1ccc2c(c1)OCCOCCOc1ccccc1OCCOCCO2
Solvent: O
Product: C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)[C@@H](OCCCO)[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Temperature: 110 °C
Reaction time: 4 h
Yield: 71.9 %

Procedure:
A mixture of 21 mg (5.1×10-5 mol) of 3β,25-dihydroxy-1α,2α-epoxy-5,7-cholestadiene, 294 μl (4.1×10-3 mol) of 1,3-propanediol, 19 mg (1.5×10-4 mol) of potassium t-butoxide and 4.8 mg (1.3×10-5 mol) of dibenzo-18-Crown-6 was stirred in an argon atmosphere at 110° C. (bath temperature) for 4 hours. The reaction mixture was poured into water, and the resulting mixture was extracted twice with ethyl acetate and washed once with a saturated aqueous sodium chloride solution. After drying the ethyl acetate layer over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by fractional thin layer chromatography (silica gel:dichloromethane:ethanol=100:15) to obtain 18 mg (72% yield) of the titled compound as a white powder.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([C:11]([Cl:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([Cl:6])=[O:5].C(OCCCCCC)(=O)[C:15]1[CH:23]=[CH:22]C(C([O-])=O)=[CH:17][CH:16]=1.[K+].S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH2:1]([C:2]1[CH:10]=[C:9]([C:11]([Cl:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([Cl:6])=[O:5])[CH2:17][CH2:16][CH2:15][CH2:23][CH3:22]
Reactant: Cc1cc(C(=O)Cl)ccc1C(=O)Cl
Reactant: CCCCCCOC(=O)c1ccc(C(=O)[O-])cc1
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: CCCCCCc1cc(C(=O)Cl)ccc1C(=O)Cl

Procedure:
This compound was prepared by the method described for monomethyl terephthaloyl chloride. Typical reagent levels were as follows: potassium monohexyl terephthalate (18.6 g, 0.64 mole), thionyl chloride (9.21 g, 0.774 mole) and 100 ml of toluene. The product was used without further purification.
Reaction SMILES: [CH3:1][S:2]([O:5][CH2:6][C:7]([NH:11][CH2:12][C:13]1[CH:14]=[C:15]2[C:24](=[C:25]3[C:30]=1[CH:29]=[CH:28][CH:27]=[CH:26]3)[CH:23]=[CH:22][C:21]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]2=1)([CH3:10])[CH2:8][OH:9])(=[O:4])=[O:3].[CH2:31]([O:33]C1C2C=CC=CC=2C2C(=C3C(=C(C=O)C=2)C=CC=C3)C=1)[CH3:32].NC(C)(CO)CO>>[CH3:1][S:2]([O:5][CH2:6][C:7]([NH:11][CH2:12][C:13]1[CH:14]=[C:15]2[C:24](=[C:25]3[C:30]=1[CH:29]=[CH:28][CH:27]=[CH:26]3)[CH:23]=[C:22]([O:33][CH2:31][CH3:32])[C:21]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]2=1)([CH3:10])[CH2:8][OH:9])(=[O:4])=[O:3]
Reactant: CC(CO)(COS(C)(=O)=O)NCc1cc2c3ccccc3ccc2c2ccccc12
Reactant: CCOc1cc2c3ccccc3c(C=O)cc2c2ccccc12
Agent: CC(N)(CO)CO
Product: CCOc1cc2c3ccccc3c(CNC(C)(CO)COS(C)(=O)=O)cc2c2ccccc12

Procedure:
Using the reductive amination procedure described in 1C, 12-ethoxy-6-chrysenecarbaldehyde (17A) and 2-amino-2-methyl-1,3-propanediol (Aldrich) gave 2-(((12-ethoxy-6-chrysenyl)methyl)amino)-2-methyl-1,3-propanediol methanesulfonate mp 202°-204° (dec) (EtOH/Et2O), (C, H, N, S).
Reaction SMILES: [CH3:1][C:2]1[CH2:6][CH:5]([CH2:7][O:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([N:15]3[C:20](=[O:21])[C:19]([CH2:22][C:23]4[CH:28]=[CH:27][C:26]([C:29]5[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=5)=[CH:25][CH:24]=4)=[C:18]([CH2:37][CH2:38][CH3:39])[N:17]4[N:40]=[CH:41][N:42]=[C:16]34)[CH2:11][CH2:10]2)[O:4][N:3]=1.C([Sn](=O)CCCC)CCC.[N:53]([Si](C)(C)C)=[N+:54]=[N-:55].C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH3:1][C:2]1[CH2:6][CH:5]([CH2:7][O:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([N:15]3[C:20](=[O:21])[C:19]([CH2:22][C:23]4[CH:28]=[CH:27][C:26]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=5[C:35]5[NH:55][N:54]=[N:53][N:36]=5)=[CH:25][CH:24]=4)=[C:18]([CH2:37][CH2:38][CH3:39])[N:17]4[N:40]=[CH:41][N:42]=[C:16]34)[CH2:11][CH2:10]2)[O:4][N:3]=1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC3CC(C)=NO3)CC2)c2ncnn12
Agent: CCCC[Sn](=O)CCCC
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3nnn[nH]3)cc2)c(=O)n([C@H]2CC[C@H](OCC3CC(C)=NO3)CC2)c2ncnn12
Temperature: 110 °C
Reaction time: 48 h

Procedure:
A mixture of 4′-[(4-{trans-4-[(3-methyl-4,5-dihydroisoxazol-5-yl)methoxy]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.4 g), dibutyltin oxide (0.088 g), azidotrimethylsilane (2.4 g) and toluene (25 mL) was stirred at 110° C. for 48 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium fluoride solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.15 g, 35%).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([NH:14][C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]1[NH:21][C:22]([C:24]1[S:25][C:26]3[CH2:27][NH:28][CH2:29][CH2:30][C:31]=3[N:32]=1)=[O:23])=[O:13])=[CH:6]2.C(N(CC)CC)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>N1C=CC=CC=1>[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([NH:14][C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]1[NH:21][C:22]([C:24]1[S:25][C:26]3[CH2:27][N:28]([S:41]([CH3:40])(=[O:43])=[O:42])[CH2:29][CH2:30][C:31]=3[N:32]=1)=[O:23])=[O:13])=[CH:6]2
Reactant: CS(=O)(=O)Cl
Reactant: O=C(N[C@@H]1CCCC[C@@H]1NC(=O)c1nc2c(s1)CNCC2)c1cc2cc(Cl)ccc2[nH]1
Agent: Cl
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N1CCc2nc(C(=O)N[C@H]3CCCC[C@H]3NC(=O)c3cc4cc(Cl)ccc4[nH]3)sc2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
(±)-cis-N1-[(5-chloroindol-2-yl)carbonyl]-N2-[(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)-carbonyl]-1,2-cyclohexanediamine hydrochloride (100 mg) was dissolved in pyridine (3 ml), triethylamine (168 μl) and methanesulfonyl chloride (48 μl) were added, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and dichloromethane and 1N hydrochloric acid were added to the residue to separate an organic layer. The resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (dichloromethane:methanol 100:1) to obtain the title compound (79 mg) as a pale yellow foamy substance.
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[S:9][CH:10]=[CH:11][N:12]=2)=[CH:6][CH:7]=1.[OH:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]([NH:23][NH2:24])=O)=[CH:16][CH:15]=1>C(O)CCC>[S:9]1[CH:10]=[CH:11][N:12]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]2[N:3]([C:21]([CH2:20][C:17]3[CH:18]=[CH:19][C:14]([OH:13])=[CH:15][CH:16]=3)=[N:23][N:24]=2)[N:4]=1
Reactant: Clc1ccc(-c2nccs2)nn1
Reactant: NNC(=O)Cc1ccc(O)cc1
Solvent: CCCCO
Product: Oc1ccc(Cc2nnc3ccc(-c4nccs4)nn23)cc1
Temperature: 120 °C
Yield: 37.2 %

Procedure:
3-Chloro-6-thiazol-2-yl-pyridazine (20 mg, 0.10 mmol) and (4-Hydroxy-phenyl)-acetic acid hydrazide (20 mg, 0.12 mmol) were combined in butanol (5 mL), fitted with water filled condenser and heated to 120° C. overnight. The reaction was concentrated in vacuo followed by purification by HPLC (10-80% CH3CN over 25 min) resulting in the title compound (11.5 mg, 37%) as a white solid.