Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[C:5]([CH2:6][CH2:7][OH:8])=[CH:4][C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2.CCN(C(C)C)C(C)C.[S:22](Cl)([CH3:25])(=[O:24])=[O:23]>C(Cl)Cl>[S:1]1[C:5]([CH2:6][CH2:7][O:8][S:22]([CH3:25])(=[O:24])=[O:23])=[CH:4][C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2
Reactant: CS(=O)(=O)Cl
Reactant: OCCc1cc2ccccc2s1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CS(=O)(=O)OCCc1cc2ccccc2s1
Temperature: 25 °C
Reaction time: 18 h
Yield: 99.8 %

Procedure:
To a solution of 2-benzo[b]thiophen-2-yl-ethanol (16.8 mmol) in CH2Cl2 (60 mL) were added DIPEA (33.6 mmol) and mesylchloride (20.2 mmol.) The mixture was stirred for 18 hrs at RT, diluted with CH2Cl2, washed with sat. NaHCO3 (3×), brine (1×), dried (MgSO4) and concentrated in vacuo to give 4.3 g (99%) of methanesulfonic acid 2-benzo[b]thiophen-2-yl-ethyl ester which was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1([CH3:30])[C:11]2[CH:10]=[CH:9][C:8]([C:12]#[C:13][C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)=[CH:7][C:6]=2[C:5]([C:25]2S[CH:27]=[CH:28][N:29]=2)=[CH:4][CH2:3]1.FC(F)(F)S(O[C:37]1C2C=C(C#CC3C=CC(C(OCC)=O)=CC=3)C=CC=2C(C)(C)C[CH:46]=1)(=O)=O>>[CH3:1][C:2]1([CH3:30])[C:11]2[CH:10]=[CH:9][C:8]([C:12]#[C:13][C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)=[CH:7][C:6]=2[C:5]([C:25]2[CH:46]=[CH:37][CH:27]=[CH:28][N:29]=2)=[CH:4][CH2:3]1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2nccs2)=CCC3(C)C)cc1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(OS(=O)(=O)C(F)(F)F)=CCC3(C)C)cc1
Product: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccccn2)=CCC3(C)C)cc1

Procedure:
Employing the same general procedure as for the preparation of ethyl 4-[(7,8-dihydro-8,8-dimethyl-5-(2-thiazolyl)naphth-2-yl)ethynyl]benzoate (Compound 67), 250.0 mg (0.52 mmol) of ethyl 4-[(5-trifluoromethylsulfonyloxy-7,8-dihydro-8,8-dimethylnaphth-3-yl)ethynyl]benzoate (Compound 66) was converted into the title compound (colorless solid) using 142.4 mg (1.045 mmol) of zinc chloride, 24.1 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) and 2-lithiopyridine (prepared by the addition of 100.6 mg (0.97 ml, 1.57 mmol) of tert-butyllithium (1.5M solution in pentane) to a cold solution (−78° C.) of 123.8 mg (0.784 mmol) of 2-bromopyridine in 1.0 mL of THF).
Reaction SMILES: [C:1]([C:3]1[C:11]2[C:10](Cl)=[N:9][C:8]([Cl:13])=[N:7][C:6]=2[N:5]([C@@H:14]2[O:26][C@H:25]([CH2:27][O:28]C(=O)C)[C@@H:20]([O:21]C(=O)C)[C@H:15]2[O:16]C(=O)C)[CH:4]=1)#[N:2].[CH3:32][OH:33]>C[O-].[Na+]>[Cl:13][C:8]1[N:9]=[C:10]([O:33][CH3:32])[C:11]2[C:3]([C:1]#[N:2])=[CH:4][N:5]([C@@H:14]3[O:26][C@H:25]([CH2:27][OH:28])[C@@H:20]([OH:21])[C@H:15]3[OH:16])[C:6]=2[N:7]=1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cc(C#N)c3c(Cl)nc(Cl)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CO
Agent: C[O-]
Agent: [Na+]
Product: COc1nc(Cl)nc2c1c(C#N)cn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 34.6 %

Procedure:
5-Cyano-2,4-dichloro-7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (5, 400 mg) was dissolved in 40 ml of methanol containing 200 mg of sodium methoxide. The solution was stirred at room temperature for 1 hr and neutralized to pH 7 with Dowex 50W-X 12 (H30) resin. The resin was filtered and the solvent was evaporated to dryness in vacuo. The residue was dissolved in water, treated with decolorizing carbon, filtered and the product slowly crystallized under an air stream. The solid was recrystallized from ethanol-water to yield 100 mg of 7, mp 194-195°. The analytical sample was dried in an Abderhalden apparatus in vacuo for 2 hr. at 110° (mp unchanged).
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.[C:26]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)(=[O:28])[CH3:27]>>[C:26]([N:29]1[CH2:34][CH2:33][N:32]([C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][N:8]([C:12]4[CH:17]=[C:16]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[N:15]=[C:14]([NH2:25])[N:13]=4)[CH2:9]3)=[CH:4][CH:3]=2)[CH2:31][CH2:30]1)(=[O:28])[CH3:27]
Reactant: CC(=O)N1CCNCC1
Reactant: CN1CCN(c2cc(N3CCc4ccc(Br)cc4C3)nc(N)n2)CC1
Product: CC(=O)N1CCN(c2ccc3c(c2)CN(c2cc(N4CCN(C)CC4)nc(N)n2)CC3)CC1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 30 starting from 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine and 1-acetylpiperazine (Aldrich Cat. No. 359513). LCMS (M+H)+: m/z=451.2.
Reaction SMILES: [OH:1][CH:2]([CH2:6][N:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[CH2:3][O:4][NH2:5].[CH2:13]([N:20]=[C:21]=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(Cl)(Cl)Cl>[CH2:13]([NH:20][C:21]([NH:5][O:4][CH2:3][CH:2]([OH:1])[CH2:6][N:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: NOCC(O)CN1CCCCC1
Reactant: O=C=NCc1ccccc1
Solvent: ClC(Cl)Cl
Product: O=C(NCc1ccccc1)NOCC(O)CN1CCCCC1

Procedure:
O-(2-hydroxy-3-piperidino-propyl)-hydroxylamine (2,53 g, 0,0145 mol) was dissolved in 40 ml abs. chloroform and 1,8 ml (0,0145 mol) benzyl isocyanate was added thereto while stirring. The mixture was stirred for 2 hours, the solution was evaporated and the residue was crystallized from ethanol-ether mixture. Yield: 2,1 g (47%). Mp.: 100-101° C.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C@@H:6]([N:11]([CH3:19])[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C@H:7]([CH3:10])[CH2:8][OH:9].C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>C(Cl)Cl>[CH3:27][S:28]([O:9][CH2:8][C@@H:7]([CH3:10])[C@H:6]([N:11]([C:12]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:18])[CH3:19])[C:2]1[O:1][CH:5]=[CH:4][CH:3]=1)(=[O:30])=[O:29]
Reactant: CS(=O)(=O)Cl
Reactant: C[C@H](CO)[C@@H](c1ccco1)N(C)C(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@H](COS(C)(=O)=O)[C@@H](c1ccco1)N(C)C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 100.7 %

Procedure:
To a solution of tert-butyl ((1S,2S)-1-(furan-2-yl)-3-hydroxy-2-methylpropyl)(methyl)-carbamate (108 mg, 0.40 mmol) in DCM (2 mL) at 0° C. was added triethylamine (81 mg, 0.112 ml, 0.80 mmol, 2 equiv) followed by methanesulfonylchloride (55 mg, 0.037 ml, 0.48 mmol, 1.2 equiv) and the solution was stirred at 0° C. for 1 hour. The solution was diluted with 10 mL DCM and washed with sat. NH4Cl solution, water and brine. After drying over MgSO4 the solution was concentrated in vacuo to give crude product 2.16a (140 mg, 99% yield). 1H NMR (CDCl3, 400 MHz) 7.38 (dd, J=1.76, 0.98 Hz, 1H) 6.35 (dd, J=3.13, 1.96 Hz, 1H) 6.31 (br. s., 1H) 5.29-5.32 (m, 1H) 4.16 (dd, J=9.98, 3.33 Hz, 1H) 3.90 (br. s., 1H) 2.89-2.96 (m, 3H) 2.68-2.75 (m, 3H) 2.55-2.67 (m, 1H) 1.48 (br. s., 9H) 1.11 (d, J=6.65 Hz, 3H)
Reaction SMILES: [CH2:1]1[CH:9]2[N:4]([CH2:5][CH:6]=[C:7]([C:10]3[C:18]4[C:13](=[N:14][CH:15]=[CH:16][CH:17]=4)[NH:12][CH:11]=3)[CH2:8]2)[CH2:3][CH2:2]1.[C:19]1([S:25](Cl)(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[CH2:1]1[CH:9]2[N:4]([CH2:5][CH:6]=[C:7]([C:10]3[C:18]4[C:13](=[N:14][CH:15]=[CH:16][CH:17]=4)[N:12]([S:25]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)(=[O:27])=[O:26])[CH:11]=3)[CH2:8]2)[CH2:3][CH2:2]1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: C1=C(c2c[nH]c3ncccc23)CC2CCCN2C1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: O=S(=O)(c1ccccc1)n1cc(C2=CCN3CCCC3C2)c2cccnc21

Procedure:
from 3-(1,2,3,5,8,8a-hexahydro-7-indolizinyl)-1H-7-Azaindole (10 mg, 0.0418 mmol), benzenesulfonyl chloride (20 mg, 0.113 mmol) and 1M NaN(TMS)2 (100 μL, 0.10 mmol) in THF (0.5 mL) at RT
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:22][C:23]([O:25]C(C)(C)C)=[O:24])[CH:5]=[CH:6][C:7]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:21])([F:20])[F:19])=[O:10].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:22][C:23]([OH:25])=[O:24])[CH:5]=[CH:6][C:7]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:20])([F:21])[F:19])=[O:10]
Reactant: Cc1cc(CC(=O)OC(C)(C)C)ccc1NC(=O)Nc1ccccc1C(F)(F)F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(CC(=O)O)ccc1NC(=O)Nc1ccccc1C(F)(F)F
Temperature: 25 °C
Reaction time: 4 h
Yield: 76.6 %

Procedure:
To a stirred solution of tert-butyl 3-methyl-4-[N′-(2-trifluoromethylphenyl)ureido]phenylacetate (1.06 g, 2.60 mmol) in CH2Cl2 (10 ml) was added TFA (10 ml) and the reaction mixture was stirred at room temperature for 4 hr. The reaction mixture was concentrated to a small volume and poured into ice-H2O. The resulting precipitate was collected under a reduced pressure and the crude solid was recrystallized from MeOH—CHCl3-IPE to give 3-methyl-4-[N′-(2-trifluoromethylphenyl)ureido]phenylacetic acid (702 mg, 77%) as a white crystalline powder. mp 262–263° C.; 1H-NMR (DMSO-d6) δ 2.24 (s, 3 H), 3.48 (s, 2 H), 7.03 (d, J=8.3 Hz, 1 H), 7.08 (s, 1 H), 7.26–7.30 (m, 1 H), 7.61–7.69 (m, 3 H), 7.88 (d, J=8.3 Hz, 1 H), 8.39 (s, 1 H), 8.55(s, 1 H), 12.28 (br s, 1 H); Anal. Calcd for C17H15F3N2O3: C, 57.96; H, 4.29; N, 7.95; F, 16.18. Found: C, 57.73; H, 4.23; N, 7.92; F, 16.05.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:15]([O:17][C:18]([C:20]1([CH2:34]I)[CH2:24][CH2:23][N:22]([C:25](=[O:33])[C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[CH2:21]1)=[O:19])[CH3:16]>>[CH2:15]([O:17][C:18]([C:20]1([CH2:34][O:14][C:11]2[CH:12]=[CH:13][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:9][CH:10]=2)[CH2:24][CH2:23][N:22]([C:25](=[O:33])[C:26]2[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=2)[CH2:21]1)=[O:19])[CH3:16]
Reactant: Oc1ccc(-c2ccc(F)cc2)cc1
Reactant: CCOC(=O)C1(CI)CCN(C(=O)c2ccc(Cl)cc2)C1
Product: CCOC(=O)C1(COc2ccc(-c3ccc(F)cc3)cc2)CCN(C(=O)c2ccc(Cl)cc2)C1

Procedure:
The title compound was prepared according to the method described for Preparation 29 using 4′-fluoro-biphenyl-4-ol and 1-(4-chloro-benzoyl)-3-iodomethyl-pyrrolidine-3-carboxylic acid ethyl ester (Preparation 13) to afford the racemate as a white solid (84 mg, 37%)
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:12]2[C:13](=[O:16])[CH2:14][O:15][C:11]=2[C:10]=1[CH2:19][N:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]([CH:42]=O)=[CH:34]1.N1CCCCC1>CO>[NH:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35](/[CH:42]=[C:14]2\[O:15][C:11]3[C:10]([CH2:19][N:20]4[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]4)=[C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH:18]=[CH:17][C:12]=3[C:13]\2=[O:16])=[CH:34]1
Reactant: O=Cc1c[nH]c2ccccc12
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2c(OCc3ccccc3)ccc3c2OCC3=O)CC1
Solvent: CO
Solvent: C1CCNCC1
Product: CC(C)(C)OC(=O)N1CCN(Cc2c(OCc3ccccc3)ccc3c2O/C(=C\c2c[nH]c4ccccc24)C3=O)CC1
Temperature: 60 °C
Reaction time: 2 h
Yield: 55.1 %

Procedure:
A solution of tert-butyl 4-{[6-(benzyloxy)-3-oxo-2,3-dihydrobenzofuran-7-yl]methyl}piperazine-1-carboxylate (0.198 g, 0.452 mmol) in methanol (1.8 mL) was added with indole-3-carboxaldehyde (0.0656 g, 0.452 mmol) and piperidine (0.0308 g, 0.362 mmol), and the mixture was stirred at 60° C. for 2 hours. The reaction mixture was cooled to room temperature, and then the precipitated yellow solid was collected by filtration to obtain tert-butyl (Z)-4-({2-[(1H-indol-3-yl)methylene]-6-(benzyloxy)-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate (0.141 g, 55%).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Br)[CH:8]=[CH2:9].[F:11][C:12]1[CH:13]=[C:14]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39][C:40]([O:42][CH2:43][CH:44]=[CH2:45])=[O:41])=[CH:35][CH:34]=2)[CH:15]=[CH:16][C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[C:22]([OH:30])[C:21]=1[CH:31]=[O:32].O>CN(C)C=O>[CH2:7]([O:30][C:22]1[C:21]([CH:31]=[O:32])=[C:20]([CH:25]=[CH:24][C:23]=1[C:26]([F:29])([F:27])[F:28])[CH2:19][O:18][C:17]1[CH:16]=[CH:15][C:14]([C:33]2[CH:34]=[CH:35][C:36]([CH2:39][C:40]([O:42][CH2:43][CH:44]=[CH2:45])=[O:41])=[CH:37][CH:38]=2)=[CH:13][C:12]=1[F:11])[CH:8]=[CH2:9]
Reactant: C=CCOC(=O)Cc1ccc(-c2ccc(OCc3ccc(C(F)(F)F)c(O)c3C=O)c(F)c2)cc1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOC(=O)Cc1ccc(-c2ccc(OCc3ccc(C(F)(F)F)c(OCC=C)c3C=O)c(F)c2)cc1
Temperature: 50 °C
Reaction time: 1.5 h
Yield: 23.7 %

Procedure:
Potassium carbonate (148 mg, 1.07 mmol) and allyl bromide (0.091 ml, 1.1 mmol) were successively added to a solution of allyl (3′-fluoro-4′-{[2-formyl-3-hydroxy-4-(trifluoromethyl)benzyl]oxy}-1,1′-biphenyl-4-yl)acetate (476 mg, 0.975 mmol) obtained in Example (12-4) in N,N-dimethylformamide (5 ml), and the mixture was stirred at 50° C. for 1.5 hours. After the reaction mixture was poured into water and the mixture was extracted with ethyl acetate, the organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=3/1) to give allyl (4′-{[3-(allyloxy)-2-formyl-4-(trifluoromethyl)benzyl]oxy}-3′-fluoro-1,1′-biphenyl-4-yl)acetate (122 mg, yield: 24%).
Reaction SMILES: [CH2:1]([N:3]1[C:12](=[O:13])[C:11]2[NH:10][CH:9]=[N:8][C:7]=2[N:6]([CH2:14][CH3:15])[C:4]1=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[Cl:22][C:23]1[CH:38]=[CH:37][C:26]([C:27]([C:29]2[CH:36]=[CH:35][C:32]([CH2:33]Br)=[CH:31][CH:30]=2)=[O:28])=[CH:25][CH:24]=1>CN(C=O)C.O>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:27]([C:29]2[CH:36]=[CH:35][C:32]([CH2:33][N:10]3[C:11]4[C:12](=[O:13])[N:3]([CH2:1][CH3:2])[C:4](=[O:5])[N:6]([CH2:14][CH3:15])[C:7]=4[N:8]=[CH:9]3)=[CH:31][CH:30]=2)=[O:28])=[CH:37][CH:38]=1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(CBr)cc1
Reactant: CCn1c(=O)c2[nH]cnc2n(CC)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCn1c(=O)c2c(ncn2Cc2ccc(C(=O)c3ccc(Cl)cc3)cc2)n(CC)c1=O
Temperature: 25 °C
Reaction time: 17 h
Yield: 54.5 %

Procedure:
To a solution of 1,3-diethylxanthine (190 mg), a synthetic process for which is described in Journal of American Chemical Society, 75, 114 (1953), in DMF (5 ml) were added potassium carbonate (189 mg) and 4-(4-chlorobenzoyl)benzyl bromide (282 mg) and the mixture was stirred at room temperature for 17 hours. This reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with saturated aqueous NaCl solution and dried over anhydrous sodium sulfate and the solvent was distilled off. The residue was purified by silica gel column chromatography (hexane: ethyl acetate=1:1) and recrystallized (ether-hexane) to provide the title compound as colorless powder (217 mg, 54%).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[O:12]1[CH2:16][CH:15]=[CH:14][C@H:13]1[C@@H:17]([OH:30])[CH2:18][NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>N1C=CC=CC=1.O>[CH3:11][C:1]1[CH:6]=[CH:5][C:4]([S:7]([O:30][C@H:17]([C@@H:13]2[CH:14]=[CH:15][CH2:16][O:12]2)[CH2:18][NH:19][C:20]([O:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[O:29])(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=C(NC[C@H](O)[C@@H]1C=CCO1)OCc1ccccc1
Solvent: O
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)O[C@@H](CNC(=O)OCc2ccccc2)[C@@H]2C=CCO2)cc1
Yield: 61.4 %

Procedure:
A solution of p-toluenesulfonyl chloride (252 mg, 1.32 mmol) in pyridine (7.0 mL), alcohol (17) (290 mg, 1.10 mmol) was stirred at 24° C. for 2 days then diluted with water (15 mL). The product was extracted into tert-butyl methyl ether (3×20 mL) then dried (MgSO4), filtered and reduced in vacuo. Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 7:93 to 20:80 gave tosylate (32) (282 mg, 61%) as a colourless oil. TLC (Rf=0.35, EtOAc:heptane 1:1), analytical HPLC single main peak, Rt=19.02 min., HPLC-MS 418.2 [M+H]+, 857.3 [2M+Na]+; [α]D11 −86.1° (c=1.103, CHCl3; δH (500 MHz, CDCl3) 2.37 (3H, s, aryl-CH3), 3.29-3.37 and 3.50-3.56 (2H total, m, CH2NH), 4.53-4.56 (2H total, m, OCH2CH═CH), 4.62-4.66 m, OCHCH═CH), 4.85-4.90 (1H, m, CHOTs), 5.02-5.08 (2H, m, OCH2Ph), 5.02 (1H, brs, NH), 5.65-5.70 and 5.94-5.98 (2H total, m, CH2CH═CH), 7.27 (2H, d, J=8.12 Hz, aromatic CH3CCH), 7.29-7.37 (5H, m, phenyl CH), 7.76 (2H, d, J=8.23 Hz, aromatic OSO2CCH); δC (125 MHz, CDCl3) 21.609 (aryl-CH3), 41.749 (CH2NHCbz), 66.833 (CH2Ph), 75.939 (OCH2CH═CH), 81.235 (CHOTs), 85.203 (OCHCH═CH), 124.702, 127.887, 128.026, 128.128, 128.504, 129.687 and 129.757 (OCH2CH═CH and aromatic CH), 133.591 (CHOSO2C quaternary), 136.368 (Cbz quaternary), 144.906 (CH3C quaternary), 156.271 (Cbz C═O).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH3:11][NH2:12].O>ClCCl>[CH3:11][NH:12][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cnccc1Cl
Reactant: CN
Solvent: O
Solvent: ClCCl
Product: CNc1ccncc1[N+](=O)[O-]
Temperature: 40 °C
Reaction time: 1 h
Yield: 98.5 %

Procedure:
To a suspension of 4-chloro-3-nitropyridine (2 g, 12.6 mmol) in dichloromethane (15 mL) was cautiously added methyl amine (25% solution in water, 10 mL, 63 mmol). The reaction mixture was heated to 40° C. After stirring for 1 h, the mixture was poured into water (20 mL), and the precipitate was collected by filtration and dried in vacuo to afford the title compound (1.9 g, yield 98%) as a yellow solid. LC-MS (ESI) m/z: 154 (M+1)+.
Reaction SMILES: [CH3:1][N:2]([CH3:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[CH3:12][O:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1>>[CH3:1][N:2]([CH3:11])[C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH:18][C:17]2[CH:19]=[CH:20][C:14]([O:13][CH3:12])=[CH:15][CH:16]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(N)cc1
Reactant: CN(C)c1ccc(C=O)cc1
Product: COc1ccc(NCc2ccc(N(C)C)cc2)cc1
Yield: 29.1 %

Procedure:
By the reaction and treatment in the same manner as in Preparation Example 1 using 4-dimethylaminobenzaldehyde (10.0 g) and 4-methoxyaniline (8.25 g) as a starting material, (4-dimethylaminophenylmethyl) (4-methoxyphenyl)amine (5 g) was obtained. melting point: 92-94° C.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]4[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.[C:24]([O:28][C:29]([N:31]([CH2:52][CH3:53])[C:32]1[C:33]([CH2:47][O:48][C:49](=[O:51])[CH3:50])=[N:34][CH:35]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:37]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>>[C:24]([O:28][C:29]([N:31]([CH2:52][CH3:53])[C:32]1[C:33]([CH2:47][O:48][C:49](=[O:51])[CH3:50])=[N:34][CH:35]=[C:36]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]5[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=5)[C:5]=4[C:4]=3[CH:3]=2)[CH:37]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25]
Reactant: Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(Br)cc3c21
Reactant: CCN(C(=O)OC(C)(C)C)c1cc(B2OC(C)(C)C(C)(C)O2)cnc1COC(C)=O
Product: CCN(C(=O)OC(C)(C)C)c1cc(-c2ccc3ncc4c(c3c2)n(-c2cn(C)nc2C)c(=O)n4C)cnc1COC(C)=O

Procedure:
The title compound was synthesized in a similar manner as described for Example 1.1 using 8-bromo-1(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Intermediate A, 0.109 mmol) and acetic acid 3-(tert-butoxycarbonyl-ethyl-amino)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylmethyl ester (stage 155.1.2) to give the title compound as an off-white solid. (HPLC: tR 2.88 min (Method A); M+H=586 MS-ES)
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[N+:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16])([O-:8])=[O:7]>>[CH3:16][O:15][C:10]1[C:9]([N+:6]([O-:8])=[O:7])=[CH:14][C:13]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:12][CH:11]=1
Reactant: COc1ccccc1[N+](=O)[O-]
Reactant: O=S(=O)(O)Cl
Product: COc1ccc(S(=O)(=O)Cl)cc1[N+](=O)[O-]
Temperature: 0 °C

Procedure:
2.5 mols (165 ml) of chlorosulphonic acid are placed in a one-liter reaction vessel equipped with a stirring system, a thermometer and a dropping funnel and the acid is cooled to about 0° C. with a mixture of ice and salt. 0.8 mol (100 ml) of 2-nitroanisole is added drop by drop and the solution is then allowed to come back to room temperature; after a contact time of 30 minutes, the reaction mixture is poured onto one fifth of its volume of crushed ice. The sulphonyl chloride precipitates in the form of an oil; this is extracted with chloroform. After evaporation of the organic phase, the sulphonyl chloride is crystallized in a benzene/petroleum ether mixture.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:22]=[CH:21][C:12]3[N:13]([CH3:20])[C:14]([NH:16][CH:17]([CH3:19])[CH3:18])=[N:15][C:11]=3[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[C:23](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH3:23])[C:9]2[CH:22]=[CH:21][C:12]3[N:13]([CH3:20])[C:14]([NH:16][CH:17]([CH3:19])[CH3:18])=[N:15][C:11]=3[CH:10]=2)[CH:5]=[CH:4][N:3]=1
Reactant: O=C([O-])[O-]
Reactant: CC(C)Nc1nc2cc(Nc3ccnc(Cl)n3)ccc2n1C
Agent: [Cs+]
Solvent: CI
Solvent: CN(C)C=O
Product: CC(C)Nc1nc2cc(N(C)c3ccnc(Cl)n3)ccc2n1C
Temperature: 25 °C
Yield: 46 %

Procedure:
To a solution of N2-isopropyl-1-methyl-1H-benzimidazole-2,5-diamine (1.46 g, 7.2 mmol) in THF (7 ml) and ethanol (21 ml) was added NaHCO3 (1.81 g, 21.6 mmol) and 2,4-dichloropyrimidine (2.68 g, 18 mmol) and the reaction was heated to 75° C. After 5 h, the reaction was filtered hot and concentrated to a gray foam. Ether was added and the solid was filtered and dried to give N5-(2-chloro-pyrimidin-4-yl)-N2-isopropyl-1-methyl-1H-benzimidazole-2,5-diamine as an off-white solid. N5-(2-chloro-pyrimidin-4-yl)-N2-isopropyl-1-methyl-1H-benzimidazole-2,5-diamine was dissolved in DMF (21 ml) and cesium carbonate (6.84 g, 21 mmol) was added After 15 min, iodomethane (0.70 ml, 11.2 mmol) was added, and the reaction was stirred at rt. After TLC showed the starting material to be consumed, the reaction was diluted with water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with water, dried over MgSO4 and concentrated to a red foam. The crude material was purified with silica gel to give the title compound as a white solid (1.10 g, 46% over two steps). 1H NMR (300 MHz, d6-DMSO) δ 7.87 (d, J=6.0 Hz, 1H), 7.22 (d, J=8.1 Hz, 1H), 7.11 (1.8 Hz, 1H), 6.82 (dd, J=8.1 and 1.8 Hz, 1H), 6.53 (d, J=7.5 Hz, 1H), 6.09 (d, J=6.0 Hz, 1H), 4.04 (m, 1H), 3.51 (s, 3H), 3.37 (s, 3H), 1.23 (d, J=6.6 Hz, 6H). MS (ESI) m/z=331 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][CH:31]=1)[O:5][C:6]1[S:7][C:8]([C:11]2[CH:15]=[C:14]([CH:16]([N:18]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19]3=[O:28])[CH3:17])[O:13][N:12]=2)=[CH:9][N:10]=1.[CH:32](O)([CH3:34])[CH3:33].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH:32]([O:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][CH:31]=1)[O:5][C:6]1[S:7][C:8]([C:11]2[CH:15]=[C:14]([CH:16]([N:18]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19]3=[O:28])[CH3:17])[O:13][N:12]=2)=[CH:9][N:10]=1)([CH3:34])[CH3:33]
Reactant: CC(C)O
Reactant: CC(c1cc(-c2cnc(Oc3cccc(O)c3)s2)no1)N1C(=O)c2ccccc2C1=O
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)Oc1cccc(Oc2ncc(-c3cc(C(C)N4C(=O)c5ccccc5C4=O)on3)s2)c1
Reaction time: 16 h
Yield: 84.1 %

Procedure:
To a solution of Example 86F (250 mg, 0.68 mmol), isopropanol (78 μL, 1.02 mmol) and triphenylphosphine (267 mg, 1.02 mmol) in tetrahydrofuran (5 mL) was added diethyl azodicarboxylate (175 μL, 1.02 mmol) at 25° C. The reaction was stirred for 16 hours and concentrated. The concentrate was purified by flash chromatography on silica gel eluting with a solvent gradient from 10% to 30% ethyl acetate in hexanes to provide 272 mg of the title compound (84%) as a off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.26 (d, J=5.88 Hz, 6H) 1.82 (d, J=6.99 Hz, 3H) 4.55-4.74 (m, 1H) 5.64 (q, J=6.99 Hz, 1H) 6.83-7.05 (m, 3H) 7.18 (s, 1H) 7.38 (t, J=8.27 Hz, 1H) 7.83-7.95 (m, 4H) 7.96 (s, 1H); MS (ESI) m/z 476.1 (M+H)+.