Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9](Cl)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Na].[CH2:20]([OH:23])[CH2:21][CH3:22]>>[NH2:1][C:2]1[N:10]=[C:9]([O:23][CH2:20][CH2:21][CH3:22])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1nc(Cl)nc2c1ncn2Cc1ccccc1
Reactant: CCCO
Agent: [Na]
Product: CCCOc1nc(N)c2ncn(Cc3ccccc3)c2n1
Reaction time: 3 h
Yield: 74 %

Procedure:
6-Amino-9-benzyl-2-chloropurine (200 mg, 0.77 mmol) and sodium propylate (316 mg, 3.85 mmol) were dissolved in 1-propanol (20 ml) and then the solution was refluxed on heating under stirring for 3 hours. The reaction mixture was evaporated in vacuo to dryness. To the residue was added water and the mixture was extracted with chloroform. The organic layer was dried on sodium sulfate and evaporated in vacuo to dryness. The residue was purified with silica gel chromatography (2% methanol/chloroform) to give the subject compound (162 mg, yield 74%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][CH:7]([N:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:6][CH2:5]2.[C:19]([O:23][CH3:24])(=[O:22])[CH:20]=[CH2:21].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:24][O:23][C:19](=[O:22])/[CH:20]=[CH:21]/[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][CH:7]([N:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:6][CH2:5]2
Reactant: C=CC(=O)OC
Reactant: CCCN(CCC)C1CCc2cc(Br)ccc2C1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CCCN(CCC)C1CCc2cc(/C=C/C(=O)OC)ccc2C1
Yield: 28.5 %

Procedure:
3.1 g (0.01 mol) of 6-bromo-2-(N,N-dipropylamino)-1,2,3,4-tetrahydronaphthalene are dissolved in 50 ml of dimethylformamide. There are added in succession to that solution 0.94 g (0.011 mol) of methyl acrylate, 22.4 mg (0.1 mmol) of palladium acetate, 121 mg (0.4 mmol) of tri-ortho-tolylphosphine and 1.6 ml (0.011 mol) of triethylamine. The mixture is heated at 125°-130° C. for 3 h 30 min. with stirring, cooled, poured into 700 ml of water, extracted with ethyl acetate and washed with a solution of LiCl. After acid to base change, 0.9 g of the expected product is obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:11]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[CH:10]([CH2:20][CH2:21][CH:22]([OH:30])[C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[C:9]2=[O:31])=[CH:4][CH:3]=1.[Br:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40]Br)=[CH:36][CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>>[Br:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][O:29][C:26]2[CH:25]=[CH:24][C:23]([CH:22]([OH:30])[CH2:21][CH2:20][CH:10]3[CH:11]([C:12]4[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=4)[N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C:9]3=[O:31])=[CH:28][CH:27]=2)=[CH:36][CH:35]=1
Reactant: BrCc1ccc(CBr)cc1
Reactant: COc1ccc(C2C(CCC(O)c3ccc(O)cc3)C(=O)N2c2ccc(F)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccc(C2C(CCC(O)c3ccc(OCc4ccc(CBr)cc4)cc3)C(=O)N2c2ccc(F)cc2)cc1

Procedure:
1-(4-Fluorophenyl)-3-[3-hydroxy-3-(4-hydroxyphenyl)-propyl]-4-(4-methoxyphenyl)-azetidin-2-one was reacted with 1,4-bisbromomethylbenzene and potassium carbonate analogously to Example IV, giving a colorless solid (29) of molecular weight 604.52 (C33H31BrFNO4); MS (ESI): 605.2 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:18])=[C:6]([C:8](=[O:17])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])[CH:7]=1.[C:19]([O-])(=O)[CH3:20].[Na+]>C(OC(=O)C)(=O)C>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:18][C:19]([CH3:20])=[C:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])[C:8]2=[O:17]
Reactant: O=C(Cc1ccccc1F)c1cc(Br)ccc1O
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: Cc1oc2ccc(Br)cc2c(=O)c1-c1ccccc1F
Temperature: 25 °C
Yield: 70.7 %

Procedure:
Intermediate 23 (5 g, 16.17 mmoles) was taken in a RB flask and to this acetic anhydride (40 ml) and sodium acetate (9.2 g, 82.03 mmoles) were added and the mixture was refluxed for 12 h. After cooling to RT, the reaction mixture was quenched by the addition of ice cold water. The solid formed was filtered and washed with water. The product was dried under vacuum to afford the title compound as off-white solid (3.81 g, 71% yield). 1H-NMR (δ ppm, CDCl3, 400 MHz): δ 8.34(d, J=2.3 Hz, 1H), 7.76(dd, J=8.8, 2.2 Hz, 1H), 7.41(m, 2H), 7.24(m, 2H), 7.18(t, J=8.9 Hz, 1H), 2.30(s, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[CH3:13][C:14]1[CH:41]=[CH:40][CH:39]=[CH:38][C:15]=1[CH2:16][N:17]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH3:37])[C@@H:18]([CH2:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=1)[CH:19]=[O:20]>C1COCC1>[CH3:13][C:14]1[CH:41]=[CH:40][CH:39]=[CH:38][C:15]=1[CH2:16][N:17]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH3:37])[C@@H:18]([CH2:21][C:22]1[CH:23]=[C:24]([F:29])[CH:25]=[C:26]([F:28])[CH:27]=1)[C@@H:19]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)[OH:20]
Reactant: Cc1ccccc1CN(Cc1ccccc1C)[C@H](C=O)Cc1cc(F)cc(F)c1
Reactant: Brc1ccccn1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1ccccc1CN(Cc1ccccc1C)[C@@H](Cc1cc(F)cc(F)c1)[C@H](O)c1ccccn1
Temperature: -78 °C
Yield: 40.8 %

Procedure:
Dissolve 2-bromopyridine (0.485 mL, 5.07 mmol) in THF (30 mL) and cool to −78° C. Add n-butyllithium (2.0 mL, 2.5 M in hexanes). Slowly add 2-(S)-[bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-propionaldehyde (1.37 g, 3.3 mmol) in THF (10 mL) and stir 2 h. Quench reaction with saturated aqueous ammonium chloride. Warm to room temperature. Wash organic layer twice with 5% aqueous citric acid, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify twice (silica gel chromatography, eluting with hexanes and ethyl acetate, and then dichloromethane and ethyl acetate) to give the title compound as a foam (0.636 g, 40%).
Reaction SMILES: C[O:2][C:3]1[CH:26]=[C:25]([O:27]C)[CH:24]=[CH:23][C:4]=1[CH2:5][C:6]1[N:15]2[N:16]=[C:17]([NH2:19])[N:18]=[C:14]2[C:13]2[CH:12]=[CH:11][C:10]([N+]([O-])=O)=[CH:9][C:8]=2[N:7]=1.COC1C=C(C=C(OC)C=1)CC1N2N=C(N)N=C2C2C=CC=CC=2N=1>>[NH2:19][C:17]1[N:18]=[C:14]2[N:15]([C:6]([CH2:5][C:4]3[CH:23]=[CH:24][C:25]([OH:27])=[CH:26][C:3]=3[OH:2])=[N:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=32)[N:16]=1
Reactant: COc1ccc(Cc2nc3cc([N+](=O)[O-])ccc3c3nc(N)nn23)c(OC)c1
Agent: COc1cc(Cc2nc3ccccc3c3nc(N)nn23)cc(OC)c1
Product: Nc1nc2c3ccccc3nc(Cc3ccc(O)cc3O)n2n1
Yield: 76 %

Procedure:
Operating as in Example 39, but employing 5-(2,4-dimethoxy-benzyl)-8-nitro-[1,2,4]triazolo[1,5-c]quinazolin-2-ylamine, prepared as described in Example 5, instead of 5-(3,5-dimethoxy-benzyl)-[1,2,4]triazolo[1,5-c]quinazolin-2-ylamine, the title compound was obtained in 76% yield.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH2:15][CH3:16])[CH2:10][C@H:9]1[C:17]([OH:19])=O)=[O:7])(C)(C)C.[C:20]1([CH:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)C(Cl)=O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[CH2:36]([NH2:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>>[CH2:36]([NH:43][C:17]([C@@H:9]1[CH2:10][C:11](=[N:13][O:14][CH2:15][CH3:16])[CH2:12][N:8]1[C:6](=[O:7])[CH:26]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:19])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: O=C(Cl)C(c1ccccc1)c1ccccc1
Reactant: CCON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Reactant: NCc1ccccc1
Product: CCON=C1C[C@@H](C(=O)NCc2ccccc2)N(C(=O)C(c2ccccc2)c2ccccc2)C1

Procedure:
Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tertbutoxycarbonyl)-4-(ethoxyimino)-2-pyrrolidinecarboxylic acid, diphenylacetyl chloride, and benzylamine the title compound was obtained in 53% purity by LC/MS. MS(ESI+): m/z=456.4.
Reaction SMILES: [Li]CCCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[B:13](OC)([O:16]C)[O:14]C.Cl>C1COCC1.O.C1COCC1>[F:6][C:7]1[C:12]([B:13]([OH:16])[OH:14])=[CH:11][CH:10]=[CH:9][N:8]=1
Reactant: COB(OC)OC
Reactant: Fc1ccccn1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: OB(O)c1cccnc1F
Temperature: -78 °C
Reaction time: 4 h

Procedure:
800 ml (1.28 mol) of n-BuLi (1.6M in hexane) are added to a solution of 188 ml (1.32 mol) of TMP in 1,000 ml of THF at -78° C. under argon. After the mixture has been stirred for 45 minutes at this temperature, 120.4 g (1.24 mol) of 2-fluoropyridine in 200 ml of THF are added in the course of 3 minutes. After the mixture has been stirred for 4 hours at -78° C., a solution of 128.8 g (1.24 mol) of trimethyl borate in 200 ml of THF is added dropwise in the course of 20 minutes. Then, 200 ml of a 1: 1 mixture of water/THF is added at 25° C., and 256 ml of concentrated HCl are added dropwise, with ice-cooling. The organic phase is separated off, and the aqueous phase is washed twice using Et2O, filtered and concentrated in vacuo. Crude yield 148.2 g.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([O:14][C:15]2[CH:16]=[N:17][N:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])[CH:19]=2)[N:3]=1.[H-].[Na+].C(CNC[CH:34]=[O:35])=O.[CH3:36]I>CN(C)C=O.COCCOC>[CH3:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9](=[CH:36][O:35][CH3:34])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([O:14][C:15]2[CH:16]=[N:17][N:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])[CH:19]=2)[N:3]=1
Reactant: O=CCNCC=O
Reactant: CI
Reactant: COC(=O)Cc1c(C)nc(C)nc1Oc1cnn(-c2ccccc2C)c1
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CN(C)C=O
Product: COC=C(C(=O)OC)c1c(C)nc(C)nc1Oc1cnn(-c2ccccc2C)c1
Temperature: 45 °C
Reaction time: 3 h

Procedure:
The intermediate methyl 2-[2,4-dimethyl-6-(1-(2-methylphenyl)-1H-pyrazol-4-yloxy)-pyrimidin-5-yl]-acetate (6.0 g, 17 mmol), sodium hydride (0.9 g, 37 mmol) and N,N-diformylmethylamine (6 ml) in a mixture of dimethylformamide (20 ml) and 1,2-dimethoxyethane (20 ml) is stirred at 45° C. for 3 hours. Methyliodide (4.2 g, 30 mmol) is added at room temperature and stirring is continued for additional 16 hours. Dilution with ether, washing with brine, drying and chromatography on silicagel (eluant ethyl acetate/hexane 3:7) gives methyl 2-[2,4-dimethyl-6-(1-(2-methylphenyl)-1H-pyrazole-4-yloxy)-pyrimidin-5-yl]-3-methoxyacrylate as a colorless oil.
Reaction SMILES: C([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:18][CH2:19][Cl:20])[CH:15]=2)[O:10][C:9]([C:21]2[N:26]=[CH:25][N:24]3[CH:27]=[CH:28][CH:29]=[C:23]3[CH:22]=2)=[CH:8]1)(C)(C)C.[CH:30]1([NH2:35])[CH2:34][CH2:33][CH2:32][CH2:31]1>>[ClH:20].[CH:30]1([NH:35][CH2:19][CH2:18][O:17][C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[O:10][C:9]([C:21]2[N:26]=[CH:25][N:24]4[CH:27]=[CH:28][CH:29]=[C:23]4[CH:22]=2)=[CH:8][C:7]3=[N:6][OH:5])[CH2:34][CH2:33][CH2:32][CH2:31]1
Reactant: CC(C)(C)ON=c1cc(-c2cc3cccn3cn2)oc2ccc(OCCCl)cc12
Reactant: NC1CCCC1
Product: Cl
Product: ON=c1cc(-c2cc3cccn3cn2)oc2ccc(OCCNC3CCCC3)cc12

Procedure:
6-(2-cyclopentylamino-ethoxy)-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one oxime, hydrochloride was prepared in 17% overall yield using the method described in example 87, starting from 6-(2-chloro-ethoxy)-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl oxime (example 87B) and cyclopentylamine.
Reaction SMILES: C([Zn:3]CC)C.[F:6][C:7]([F:12])([F:11])[C:8]([OH:10])=[O:9].CC>C1(C)C=CC=CC=1>[F:6][C:7]([F:12])([F:11])[C:8]([O-:10])=[O:9].[Zn+2:3].[F:6][C:7]([F:12])([F:11])[C:8]([O-:10])=[O:9]
Reactant: O=C(O)C(F)(F)F
Reactant: CC[Zn]CC
Agent: CC
Solvent: Cc1ccccc1
Product: O=C([O-])C(F)(F)F
Product: [Zn+2]
Temperature: -40 °C
Reaction time: 0.5 h

Procedure:
A solution of diethyl zinc (27.5 mL, 1.1M in toluene) was slowly added to a solution of trifluoroacetic acid (2.77 mL) in dry toluene at -40° C. The reaction temp and the extent of ethane evolution was monitored. After stirring at -40° C. for 30 min, the solution was warmed to room temperature and trifluoroacetic acid (2.77 mL) was slowly added. The mixture was stirred overnight at room temperature, followed by refluxing for 2 h. A foaming suspension with a slight violet tint was formed. All volatiles were evaporated and the solid was dried at 80° C. under high vacuum. Yield: 7.65 g; 13C-NMR (75 MHz, Methanol-d4): 117.93 ppm (q, I=290.3 Hz, CF3), 163.7 ppm (q, I=36.6 Hz, CO).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:13]2[C:14](=[O:17])[O:15][CH2:16][C:12]=2[CH2:11][C:10](NC)=[C:9]1[C:20]([O:22][CH2:23][CH3:24])=[O:21].C1C[O:28]CC1.Cl>O>[OH:28][C:10]1[CH2:11][C:12]2[CH2:16][O:15][C:14](=[O:17])[C:13]=2[CH:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])[C:9]=1[C:20]([O:22][CH2:23][CH3:24])=[O:21]
Reactant: C1CCOC1
Reactant: CCOC(=O)C1=C(NC)CC2=C(C(=O)OC2)C1c1ccccc1C
Agent: Cl
Solvent: O
Product: CCOC(=O)C1=C(O)CC2=C(C(=O)OC2)C1c1ccccc1C
Reaction time: 1 h

Procedure:
10 mmol of ethyl 7-(2-methylphenyl)-5-methylamino-1-oxo-1,3,4,7-tetrahydrobenzo[c]furan-6-carboxylate are dissolved in 50 mmol of THF, 3 ml of concentrated HCl and 5 ml of water are added, and the mixture is boiled for 1 hour and then concentrated. The substance is identical to that from Example 3a.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:21][CH2:20][C@@:19]2([CH3:22])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:18]2[CH2:17][CH2:16][C@@:15]2([CH3:23])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:14])[CH3:13])[CH2:3]1.Cl.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=1.CCOCC>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:25]([O:1][C@@H:2]1[CH2:21][CH2:20][C@@:19]2([CH3:22])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:18]2[CH2:17][CH2:16][C@@:15]2([CH3:23])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:14])[CH3:13])[CH2:3]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=1
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: O=C(Cl)c1cccnc1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCOCC
Solvent: c1ccncc1
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](OC(=O)c5cccnc5)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 90 °C
Yield: 95.3 %

Procedure:
To 3α-hydroxy-5α-pregnan-20-one (464 mg, 318.5 g/m, 1.5 mmol) and 4-dimethylaminopyridine (DMAP, 195 mg, 122.17 g/m, 1.6 mmol) dissolved in 10 mL of dry pyridine was added nicotinoyl chloride hydrochloride (285 mg, 178.02 g/m, 1.6 mmol). The reaction mixture was heated at 90° C. for 5 hours and poured into 300 mL of ether. The organic layer was washed twice with saturated sodium bicarbonate, twice with water, dried over magnesium sulfate, and concentrated in vacuo to give the crude product. The crude material was filtered through a bed of silica gel using hexane/ethyl acetate (50:50) elution. The first two fractions gave the titled compound (604 mg, 421 6/m, 1.43 mmol, 96%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(N(CC)CC)C.[CH:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[S:39][CH:40]([C:44](O)=[O:45])[C:41](O)=[O:42])([CH3:32])[CH3:31]>C(Cl)Cl>[OH:45][C:44]1[CH:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=2)[O:10][C:41](=[O:42])[C:40]=1[S:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[CH:30]([CH3:32])[CH3:31]
Reactant: CC(=O)c1cccc(C)c1
Reactant: CC(C)c1ccccc1SC(C(=O)O)C(=O)O
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cccc(-c2cc(O)c(Sc3ccccc3C(C)C)c(=O)o2)c1

Procedure:
The title compound was prepared by Method A using 3'-methylacetophenone (0.87 g, 6.46 mmol), trimethylsilyl triflate (1.44 g, 6.46 mmol), triethylamine (0.653 g, 6.46 mmol), methylene chloride (20 mL), and diethyl ester of [(2-isopropylphenyl)thio]propanedioic acid (1.0 g, 3.23 mmol). m.p. 161-162° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.25 (d, 6H), 2.39 (s, 3H), 3.42 (m, 1H), 6.86 (s, 1H), 6.92 (d, 1H), 7.07 (t, 1H), 7.13 (t, 1H), 7.28 (d, 1H), 7.39 (d, 1H), 7.4 (t, 1H), 7.64 (d, 1H), 7.67 (s, 1H).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([C:14](=[O:22])[N:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])[CH:13]=1)[C:7]([O:9]C)=[O:8])(=[O:3])[CH3:2].CO.O.[Li+].[OH-]>C1COCC1>[C:1]([C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([C:14](=[O:22])[N:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])[CH:13]=1)[C:7]([OH:9])=[O:8])(=[O:3])[CH3:2]
Reactant: CCCN(CCC)C(=O)c1cc(C(C)=O)cc(C(=O)OC)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CCCN(CCC)C(=O)c1cc(C(C)=O)cc(C(=O)O)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.1 %

Procedure:
To a solution of methyl 3-acetyl-5-(dipropylcarbamoyl)benzoate (38 mg, 0.125 mmol) in a mixture of THF (0.1 mL), MeOH (0.2 mL) and H2O (0.5 mL), was added LiOH (8.9 mg, 0.374 mmol) and the mixture was stirred at room temperature for 1 h. The mixture was concentrated and partitioned between ethyl acetate and H2O. The aqueous layer was washed with ethyl acetate twice and acidified with 1N HCl solution to pH around 2˜3. The aqueous layer was extracted with ethyl acetate 3 times and the combined organic layers were dried over sodium sulfate and concentrated under vacuum to give the title compound (35 mg, 97.2% yield): 1H NMR (CD3OD, 500 MHz) δ ppm 0.78 (3H, m), 1.03 (3H, t, J=5 Hz), 1.62 (2H, m), 1.77 (2H, m), 2.69 (3H, s), 3.23 (2H, m), 3.52 (2H, m), 8.17 (1H, m), 8.21 (1H, m), 8.68 (1H, m). HPLC retention time: 1.687 min (method A). MS (ESI) (M+H)+ 292.23.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:6][O:7][CH:8]1[CH2:12][CH2:11][N:10]([C:13]2[N:33]=[C:16]3[CH:17]=[CH:18][C:19]([NH:21][C:22]([C:24]4[N:28]([CH3:29])[N:27]=[CH:26][C:25]=4[C:30]([OH:32])=O)=[O:23])=[CH:20][N:15]3[N:14]=2)[CH2:9]1>>[CH3:6][O:7][CH:8]1[CH2:12][CH2:11][N:10]([C:13]2[N:33]=[C:16]3[CH:17]=[CH:18][C:19]([NH:21][C:22]([C:24]4[N:28]([CH3:29])[N:27]=[CH:26][C:25]=4[C:30]([N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[O:32])=[O:23])=[CH:20][N:15]3[N:14]=2)[CH2:9]1
Reactant: C1CCNC1
Reactant: COC1CCN(c2nc3ccc(NC(=O)c4c(C(=O)O)cnn4C)cn3n2)C1
Product: COC1CCN(c2nc3ccc(NC(=O)c4c(C(=O)N5CCCC5)cnn4C)cn3n2)C1

Procedure:
Using pyrrolidine and 5-[2-(3-Methoxy-pyrrolidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylcarbamoyl]-1-methyl-1H-pyrazole-4-carboxylic acid, the title compound was prepared in the same manner as described for example 2. Off white solid (72 mg, 53%). MS: m/z=439 (M+H+).
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[NH:24]1[CH2:29][CH2:28][CH2:27][CH:26]([C:30]#[N:31])[CH2:25]1>CN1C(=O)CCC1.CS(C)=O.CO>[C:30]([CH:26]1[CH2:27][CH2:28][CH2:29][N:24]([C:2]2[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]3[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=3)[CH:3]=2)[CH2:25]1)#[N:31]
Reactant: CC(C)(O)c1ccc(C(=O)Nc2cc(Cl)n3nccc3n2)cc1
Reactant: N#CC1CCCNC1
Solvent: CS(C)=O
Solvent: CO
Solvent: CN1CCCC1=O
Product: CC(C)(O)c1ccc(C(=O)Nc2cc(N3CCCC(C#N)C3)n3nccc3n2)cc1
Temperature: 25 °C
Yield: 85.1 %

Procedure:
A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 0.151 mmol) and piperidine-3-carbonitrile (33 mg, 0.302 mmol) in NMP (0.950 mL) was stirred at 85° C. overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC, 35-60% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a orange solid (52 mg, 85%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (s, 6H) 1.73-2.11 (m, 4H) 3.25-3.34 (m, 1H) 3.53-3.63 (m, 1H) 3.68-3.79 (m, 1H) 3.98 (dd, J=12.51, 2.65 Hz, 1H) 4.12-4.23 (m, 1H) 6.38 (d, J=2.27 Hz, 1H) 7.46 (s, 1H) 7.60 (d, J=8.59 Hz, 2H) 8.00 (d, J=8.59 Hz, 2H) 8.12 (d, J=2.27 Hz, 1H) 10.93 (s, 1H). ESI-MS: m/z 405.3 (M+H)+.
Reaction SMILES: C([NH:11][C:12](=[NH:41])[NH:13][C:14]1[CH:40]=[CH:39][C:17]([C:18]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][C:29]([O:31]CC3C=CC=CC=3)=[O:30])[CH2:22][CH2:21]2)=[O:19])=[CH:16][CH:15]=1)(OCC1C=CC=CC=1)=O.O.C(O)(=O)C>CO.[Pd]>[NH:13]([C:14]1[CH:15]=[CH:16][C:17]([C:18]([N:20]2[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])[CH2:24][CH2:25]2)=[O:19])=[CH:39][CH:40]=1)[C:12]([NH2:41])=[NH:11]
Reactant: N=C(NC(=O)OCc1ccccc1)Nc1ccc(C(=O)N2CCN(CCCC(=O)OCc3ccccc3)CC2)cc1
Agent: [Pd]
Solvent: O
Solvent: CO
Solvent: CC(=O)O
Product: N=C(N)Nc1ccc(C(=O)N2CCN(CCCC(=O)O)CC2)cc1

Procedure:
A solution of 1 g of benzyl 4-(4-(4-(3-CBZ-guanidino)benzoyl)piperazin-1-yl)butyrate (FAB 558; obtainable by condensing 4-(3-CBZ-guanidino)benzoic acid with benzyl 4-(piperazin-1-yl)butyrate) in a mixture of 38 ml of methanol, 6 ml of water and 6 ml of acetic acid is hydrogenated on 0.6 g of 5% Pd/C at 20° and 1 bar until the uptake of H2 has ceased. It is filtered, the filtrate is evaporated and the residue is recrystallized from ethyl acetate to give 4-(4-(4-guanidinobenzoyl)piperazin-1-yl)butyric acid, FAB 334.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[CH:8][N:7]=2)[CH2:3][CH2:2]1.C(N)CN>C(O)C.[Pd]>[CH:1]1([CH2:4][O:5][C:6]2[N:7]=[CH:8][C:9]([NH2:12])=[CH:10][CH:11]=2)[CH2:2][CH2:3]1
Reactant: O=[N+]([O-])c1ccc(OCC2CC2)nc1
Agent: [Pd]
Solvent: NCCN
Solvent: CCO
Product: Nc1ccc(OCC2CC2)nc1
Reaction time: 2.5 h
Yield: 23.7 %

Procedure:
To a solution of 2-(cyclopropylmethoxy)-5-nitropyridine (2.0 g) in ethanol (10.0 mL) was added Pd/C (0.500 g) and ethylene diamine (5.0 mL). The reaction mixture was subjected for hydrogenation in Parr apparatus under 40 psi for 2-3 h. The reaction mass was quenched in water and extracted with DCM and concentrated the organic layer to afford 0.400 g of the desired product. 1HNMR (CDCl3): δ 0.31-0.32 (m, 2H), 0.43-0.46 (m, 2H), 1.07-1.12 (m, 1H), 3.62 (d, J=6.6 Hz, 2H), 4.25 (s, 2H), 6.24 (d, J=6.6 Hz, 1H), 6.89 (s, 1H), 7.05 (dd, J=3.0 Hz & 2.4 Hz, 1H); MS [M+H]+: 165.13.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1(S(C)(=O)=O)[CH:14]=[CH:13][C:12]([CH:15]=CC2C=CC=CC=2)=[CH:11][CH2:10]1.[OH:27][C:28]1C=CC(C=O)=C[CH:29]=1.ClCCCCCC[OH:43].C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+].C(OC(=O)C)(=O)C>O.CC(=O)CC>[C:28]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([CH:15]=[O:43])=[CH:13][CH:14]=1)(=[O:27])[CH3:29]
Reactant: O=Cc1ccc(O)cc1
Reactant: CS(=O)(=O)C1(OCCCCCCO)C=CC(C=Cc2ccccc2)=CC1
Reactant: OCCCCCCCl
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)OC(C)=O
Solvent: CCC(C)=O
Product: CC(=O)OCCCCCCOc1ccc(C=O)cc1
Temperature: 25 °C

Procedure:
An absorption spectrum was taken using the procedures described in Example 1 of the monomeric dipole 4-(6-hydroxyhexyloxy)-4-methylsulfonylstilbene, which has the structural formula: ##STR63## and was prepared as follows: First, 4-(6-acetoxyhexyloxy)benzaldehyde was prepared as follows: A mixture of 81.0 g (0.66 mol) of 4-hydroxybenzaldehyde, 99.7 g (0.73 mol) of 6-chloro-1-hexanol, 70.3 g (0.66 mol) of sodium carbonate, 49.7 g (0.33 mol) of sodium iodide, and 250 mL of 2-butanone was stirred mechanically and heated at reflux for 72 hours. The cooled reaction mixture was filtered, and the solvent was removed at reduced pressure to deposit the 4-(6-hydroxyhexyloxy)benzaldehyde as a brown oil. This oil was dissolved in 200 mL of pyridine, and 74.3 g (0.73 mol) of acetic anhydride was added dropwise with stirring. After the addition was completed, the reaction mixture was heated at reflux for 6 hours, and then cooled to room temperature. The mixture was poured onto 500 mL of water, and the product was extracted into dichloromethane (3 times using 250 mL each time). The combined organic extracts were washed successively with 5% aqueous HCl (2 times using 250 mL each time), and with saturated aqueous NaCl (250 mL). The organic layer was dried over MgSO4, was filtered, and the solvent was removed. The tan oily residue was fractionally distilled at reduced pressure, collecting the product 4-(6-acetoxyhexyloxy)-benzaldehyde at 190°-224° C. and pressure of 0.04 mm. The yield was 84.2 g, which is 48% of theoretical. Proton NMR was performed as in the Examples. 1H NMR (CDCl3) δ: 1.4 (m, 4H), 1.6 (m, 2H), 1.75 (m, 2H), 2.00 (s, 3H), 4.0 (m, 4H), 6.92 (d, 2H), 7.78 (d, 2H), 9.80 (s, 1H).