Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[S:10][C:9]2=[CH:11][C:12]3[CH:16]=[C:15]([Sn](CCCC)(CCCC)CCCC)[S:14][C:13]=3[CH:30]=[C:8]2[CH:7]=1)CCC.C(OC([N:46]1[CH2:50][CH2:49][CH2:48][CH:47]1[C:51]1[N:52](COCC[Si](C)(C)C)[CH:53]=[C:54](Br)[N:55]=1)=O)(C)(C)C>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:46]1[CH2:50][CH2:49][CH2:48][CH:47]1[C:51]1[NH:55][C:54]([C:15]2[S:14][C:13]3[CH:30]=[C:8]4[CH:7]=[C:6]([C:54]5[NH:55][C:51]([CH:47]6[CH2:48][CH2:49][CH2:50][NH:46]6)=[N:52][CH:53]=5)[S:10][C:9]4=[CH:11][C:12]=3[CH:16]=2)=[CH:53][N:52]=1
Reactant: CC(C)(C)OC(=O)N1CCCC1c1nc(Br)cn1COCC[Si](C)(C)C
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc2cc3sc([Sn](CCCC)(CCCC)CCCC)cc3cc2s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: c1nc(C2CCCN2)[nH]c1-c1cc2cc3sc(-c4cnc(C5CCCN5)[nH]4)cc3cc2s1
Temperature: 25 °C

Procedure:
Pd(PPh3)4 (61 mg, 0.053 mmol) was added to a degassed solution of 2,6-bis(tri-n-butylstannyl)-benzo[1,2-b:4,5-b′]dithiophene (202 mg, 0.26 mmol) and 2-[4-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (260 mg, 0.58 mmol) in toluene (4 mL). The reaction was refluxed for 24 hours, then cooled to room temperature and filtered through CELITE and a palladium scavenging column (Stratospheres™ PL-Guanidine MP SPE+, Part #: PL3514-CM89). The solids were rinsed twice with toluene. The filtrate was concentrated and the crude product purified by flash chromatography to yield the desired, fully protected product (100 mg, 41%). LCMS-ESI+: calculated for C46H68N6O6S2Si2: 920.42; observed [M+1]+: 921.45.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.[CH3:13][O:14][C:15](=[O:22])[C@H:16]([CH2:18][CH2:19][S:20][CH3:21])[NH2:17]>>[CH3:13][O:14][C:15](=[O:22])[CH:16]([NH:17][C:10](=[O:12])[CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=1)[CH2:18][CH2:19][S:20][CH3:21]
Reactant: COC(=O)[C@@H](N)CCSC
Reactant: O=C(O)CCc1ccc(O)cc1
Product: COC(=O)C(CCSC)NC(=O)CCc1ccc(O)cc1
Yield: 91 %

Procedure:
Following the same procedure of Example 4 except that 3-(4-hydroxyphenyl)propionic acid (1.0 g, 6.0 mmol) and methionine methyl ester (1.08 g, 6.6 mmol) were used, 1.7 g of the title compound was obtained. The compound was finally purified by silica gel column chromatography (column size: 25 mm×150 mm, silica gel 70-230 mesh, eluent: hexane/EtOAc (1/1)). The results of analyses of the compound are as follows:
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]([C:7]([OH:9])=O)=[CH:5][N:6]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:46][CH2:47][C:48]1[C:57](=[O:58])[C:56]2[C:51](=[CH:52][C:53]([Cl:59])=[CH:54][CH:55]=2)[N:50]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH:49]=1>C(Cl)Cl>[Cl:59][C:53]1[CH:52]=[C:51]2[C:56]([C:57](=[O:58])[C:48]([CH2:47][NH:46][C:7]([C:4]3[S:3][C:2]([Br:1])=[N:6][CH:5]=3)=[O:9])=[CH:49][N:50]2[C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[CH:55][CH:54]=1
Reactant: NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O
Reactant: O=C(O)c1cnc(Br)s1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1cnc(Br)s1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 93.1 %

Procedure:
To a stirred solution of 2-bromothiazole-5-carboxylic acid (241 mg, 1.16 mmol) and N,N-diisopropylethylamine (409 mg, 552 μL, 3.16 mmol) in methylene chloride was added (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) (559 mg, 1.26 mmol). After 15 min., 3-(aminomethyl)-7-chloro-1-phenylquinolin-4(1H)-one (intermediate D) (300 mg, 1.05 mmol) was added. The reaction mixture was stirred at room temperature. The mixture was diluted with CH2Cl2 and washed with water followed by 1N aqueous HCl and finally saturated aqueous sodium carbonate solution. The organic layer was dried (Na2SO4), filtered and concentrated. The product 2-bromo-thiazole-5-carboxylic acid (7-chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amide (464 mg, 93%) was obtained without further purification.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:14][C:15]2[CH:19]=[CH:18][NH:17][N:16]=2)[N:3]=1.[C:20]([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)(=[O:22])[CH3:21]>>[CH3:13][O:12][C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([C:27]1[CH:28]=[C:23]([C:20](=[O:22])[CH3:21])[CH:24]=[CH:25][CH:26]=1)=[N:3][C:4]([NH:14][C:15]1[CH:19]=[CH:18][NH:17][N:16]=1)=[CH:5]2
Reactant: COc1ccc2c(Cl)nc(Nc3cc[nH]n3)cc2c1
Reactant: CC(=O)c1cccc(B(O)O)c1
Product: COc1ccc2c(-c3cccc(C(C)=O)c3)nc(Nc3cc[nH]n3)cc2c1

Procedure:
Similar procedure as described in example 131 was used, starting from (1-chloro-6-methoxy-isoquinolin-3-yl)-(1H-pyrazol-3-yl)-amine and 3-acetyl-phenylboronic acid to give 1-{3-[6-methoxy-3-(1H-pyrazol-3-ylamino)-isoquinolin-1-yl]-phenyl}-ethanone. LC-MS m/e 359(MH+).
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[F:13][C:14]1[CH:15]=[C:16]([NH2:24])[C:17](=[CH:21][C:22]=1[F:23])[C:18]([OH:20])=O.Cl.[CH2:26]([O:33][NH2:34])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C>C1COCC1>[NH2:24][C:16]1[CH:15]=[C:14]([F:13])[C:22]([F:23])=[CH:21][C:17]=1[C:18]([NH:34][O:33][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:20]
Reactant: Nc1cc(F)c(F)cc1C(=O)O
Reactant: NOCc1ccccc1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Nc1cc(F)c(F)cc1C(=O)NOCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 69.6 %

Procedure:
Carbonyldiimidazole (6.1 g, 37 mmol) was added to a suspension of 4,5-difluoroanthranilic acid (5.40 g, 31 mmol) in 250 mL of THF, and the mixture was stirred for 24 hours at 25° C. O-benzylhydroxylamine hydrochloride (4.95 g, 31 mmol) and triethylamine (5.2 mL, 37 mmol) were added, and the mixture was heated to reflux for 4 hours. The reaction mixture was concentrated and washed with 1N HCl, saturated NaHCO3, brine, and dried over magnesium sulfate. The solution was concentrated to give 6.0 g of the title compound as a solid, mp 125-126° C.
Reaction SMILES: [NH2:1][C:2]1[CH:34]=[CH:33][C:5]([C:6]([O:8][CH2:9][CH2:10][O:11][C:12](=[O:32])[CH2:13][CH2:14][C@H:15]([N:19]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]2=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:16]([OH:18])=[O:17])=[O:7])=[CH:4][CH:3]=1.Cl.N([O-])=O.[Na+].[N-:40]=[N+:41]=[N-].[Na+]>CC(C)=O.O>[N:1]([C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH2:10][O:11][C:12](=[O:32])[CH2:13][CH2:14][C@H:15]([N:19]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[C:26]3[C:31]2=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:16]([OH:18])=[O:17])=[O:7])=[CH:33][CH:34]=1)=[N+:40]=[N-:41]
Reactant: Nc1ccc(C(=O)OCCOC(=O)CC[C@@H](C(=O)O)n2c3ccccc3c3ccccc32)cc1
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: [N-]=[N+]=Nc1ccc(C(=O)OCCOC(=O)CC[C@@H](C(=O)O)n2c3ccccc3c3ccccc32)cc1
Reaction time: 0.08 h
Yield: 84.2 %

Procedure:
To a stirred solution of 25 (0.38 g, 0.83 mmol) in acetone (8 mL) was added 5% HCl (8 mL) at 0° C. and the solution was stiffed for 5 min NaNO2 (0.70 g, 1.0 mmol) in 1 mL water was added dropwise to the above solution causing an immediate color change from colorless to orange. After 20 min of stiffing at 0° C., NaN3 (0.107 g, 1.65 mmol) in 1 mL water was added dropwise to the reaction mixture causing an immediate color changed from orange to colorless to pale yellow. The reaction mixture was stiffed for additional 30 min and extracted with ethyl acetate (100 mL), washed with water (30 mL) and brine (30 mL). The final organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure to obtain (S)-5-(2-(4-azidobenzoyloxy)ethoxy)-2-(9H-carbazol-9-yl)-5-oxopentanoic acid 26 (0.34 g, 85%) as an off white gummy solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:13][C:14]#[N:15])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.ClC1C=CC=CC=1C1C=CC=CC=1CC(N)=[NH:32]>>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:13][C:14]([NH2:32])=[NH:15])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: N#CCC1(c2ccc(Cl)cc2)CCCC1
Reactant: N=C(N)Cc1ccccc1-c1ccccc1Cl
Agent: Cl
Product: N=C(N)CC1(c2ccc(Cl)cc2)CCCC1
Yield: 80.21 %

Procedure:
2-[1-(4-chlorophenyl)-cyclopentyl]-acetamidine HCl salt (26-02) (6 g, 80.21%) was synthesized from [1-(4-chlorophenyl)-cyclopentyl]-acetonitrile (25-02) (6 g, 27.39 mmol) as a white gummy solid as a crude product following the procedure as described for 2-(2′-chloro-biphenyl-2-yl)-acetamidine hydrochloride salt (5-02).
Reaction SMILES: Br[C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:16]2[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=2)=[CH:10]3)=[CH:4][CH:3]=1.[CH3:24][N:25]1[CH2:30][CH2:29][CH:28]([CH:31]2[CH2:35][CH2:34][CH2:33][NH:32]2)[CH2:27][CH2:26]1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:21]([N:20]1[C:16]([C:11]2[N:12]=[C:13]3[C:14]4[CH:15]=[C:2]([N:32]5[CH2:33][CH2:34][CH2:35][CH:31]5[CH:28]5[CH2:27][CH2:26][N:25]([CH3:24])[CH2:30][CH2:29]5)[CH:3]=[CH:4][C:5]=4[O:6][CH2:7][CH2:8][N:9]3[CH:10]=2)=[N:17][CH:18]=[N:19]1)([CH3:23])[CH3:22]
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1cc(Br)ccc1OCC2
Reactant: CN1CCC(C2CCCN2)CC1
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)n1ncnc1-c1cn2c(n1)-c1cc(N3CCCC3C3CCN(C)CC3)ccc1OCC2
Temperature: 110 °C
Reaction time: 1 h

Procedure:
A mixture of 13-bromo-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (200 mg, 0.540 mmol), 1-methyl-4-(pyrrolidin-2-yl)piperidine (108 mg, 0.640 mmol), Pd(PtBu3)2 (7 mg, 0.015 mmol), NaOtBu (155 mg, 1.62 mmol) in toluene (2 ml) in a seal tube was degassed with N2 for three times. The resulting mixture was stirred at 110° C. for 1 h. The solid was filtered off through Celite. The filtrate was concentrated to give the crude product, which was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford 161. The (R) and (S) enantiomers were further purified and separated by chiral HPLC (AD column, 30% EtOH (0.1% DEA) in n-Hexane isocratic) to give 6 mg of one enantiomer and 11 mg of the other (5% total yield)
Reaction SMILES: CS([O:5][CH2:6][CH:7](O)[CH2:8][C:9]1[C:10]([C:16]2[NH:17][C:18]3[C:23]([CH:24]=2)=[C:22]([F:25])[CH:21]=[CH:20][CH:19]=3)=[N:11][C:12]([Cl:15])=[CH:13][CH:14]=1)(=O)=O.[H-].[Na+].O>CN(C=O)C>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]2[CH2:8][CH:7]([CH2:6][OH:5])[N:17]3[C:18]4[CH:19]=[CH:20][CH:21]=[C:22]([F:25])[C:23]=4[CH:24]=[C:16]3[C:10]=2[N:11]=1
Reactant: CS(=O)(=O)OCC(O)Cc1ccc(Cl)nc1-c1cc2c(F)cccc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: OCC1Cc2ccc(Cl)nc2-c2cc3c(F)cccc3n21
Temperature: 0 °C
Reaction time: 2 h
Yield: 92.5 %

Procedure:
A solution of 3-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)-2-hydroxypropyl methanesulfonate (100 mg, 0.25 mmol) in DMF (5 mL) was stirred under N2 at 0° C. After NaH (30 mg, 60% in mineral oil, 0.75 mmol) was added, the mixture was stirred at 0° C. for 0.5 h and RT for 2 h. After cooling to 0° C., water was added and the mixture extracted with EtOAc. Then the organic layer was washed with water, brine, dried over Na2SO4 and concentrated on a rotary evaporator. The residue was purified by column chromatography (PE:EA=2:1˜1:1) to give the product of (2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)methanol (70 mg, yield: 92%). 1H-NMR (CDCl3, 400 MHz) δ 7.50 (d, J=7.6 Hz, 1H), 7.37 (s, 1H), 7.13˜7.19 (m, 3H), 6.78 (t, J=7.6 Hz, 1H), 4.79˜4.84 (m, 1H), 3.69˜3.73 (m, 1H), 3.60˜3.62 (m, 1H), 3.38˜3.42 (m, 1H), 3.24 (d, J=16.4 Hz, 1H). MS (M+H)+: 303/305.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.CN(C)[C:8](=[O:20])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[NH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:31]([O:33][CH3:34])=[O:32])[CH:29]=2)[CH:24]=[CH:23]1.C>CO>[C:8]([C:24]1[C:25]2[C:30](=[CH:29][C:28]([C:31]([O:33][CH3:34])=[O:32])=[CH:27][CH:26]=2)[NH:22][CH:23]=1)(=[O:20])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCCCCCCCCC(=O)N(C)C
Reactant: COC(=O)c1ccc2cc[nH]c2c1
Solvent: O=P(Cl)(Cl)Cl
Solvent: CO
Product: CCCCCCCCCCCC(=O)c1c[nH]c2cc(C(=O)OC)ccc12
Temperature: 90 °C
Yield: 39.2 %

Procedure:
Phosphorus oxychloride (27.5 ml) was added dropwise during 20 minutes to stirred N,N-dimethyldodecanamide (84.9 g) at room temperature. The temperature of the mixture rose during the addition to 50° C. The mixture was stirred and heated at 90° C. for 15 minutes and then methyl indole-6-carboxylate (33.4 g) was added portionwise to the stirred mixture during 10 minutes, the temperature of the mixture being maintained at 90° C. during the addition. The mixture was then stirred for 2 hours at 90° C. and was then poured onto ice. The aqueous mixture was extracted with chloroform (3×300 ml) and the extract was dried over magnesium sulphate and was evaporated to give a red brown oil. The oil was dissolved in boiling methanol (100 ml), the solution was treated with charcoal and the solution was filtered and cooled (0° C.) to give methyl 3-(n-dodecanoyl)indole-6-carboxylate (26.7 g), in the form of a buff solid, m.p. 167°-169° C.
Reaction SMILES: C([Mg]Cl)#C.[CH2:5]1[CH2:9][O:8][CH2:7][CH2:6]1.[O:10]1CC[C:13](=O)[CH2:12][CH2:11]1.[Cl-].[NH4+]>C(OCC)C>[C:12]([C:11]1([OH:10])[CH2:6][CH2:7][O:8][CH2:9][CH2:5]1)#[CH:13]
Reactant: C1CCOC1
Reactant: O=C1CCOCC1
Agent: C#C[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: C#CC1(O)CCOCC1

Procedure:
A solution of ethynylmagnesium chloride in THF (0.5 M, 120 mL, 60 mmol) was added with cooling in an ice-water bath to a solution of tetrahydro-4H-pyran-4-one (4.96 g, 50 mmol) (Aldrich) in diethyl ether (300 mL) dropwise over 15 min. The mixture was stirred with cooling for 3 h. Aqueous ammonium chloride solution (100 mL, 15% W/V) was then added and mixture extracted with ether (2×200 mL). The ether layers were washed with saturated aqueous sodium chloride solution (200 mL), then combined, dried (MgSO4), filtered and concentrated to give 4-Ethynyl-tetrahydro-pyran-4-ol as a colorless oil that solidified on standing. (Yield 6.01 g, 96.2%).
Reaction SMILES: [CH3:1][CH:2]1[CH:9]2[CH:5]([CH2:6][NH:7][CH2:8]2)[C:4]2[S:10][CH:11]=[CH:12][C:3]1=2.C(N(CC)CC)C.Cl[C:21]([O:23][CH2:24][CH3:25])=[O:22]>C(Cl)Cl>[CH2:24]([O:23][C:21]([N:7]1[CH2:6][CH:5]2[CH:9]([CH:2]([CH3:1])[C:3]3[CH:12]=[CH:11][S:10][C:4]=32)[CH2:8]1)=[O:22])[CH3:25]
Reactant: CCOC(=O)Cl
Reactant: CC1c2ccsc2C2CNCC12
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)N1CC2c3sccc3C(C)C2C1
Temperature: 22 °C
Yield: 68 %

Procedure:
A 0° C. solution of the product from step h) (258 mg, 1.19 mmol) in CH2Cl2 (6 ml) was treated with triethylamine (497 μl, 3.57 mmol) and ethyl chloroformate (227 μl, 2.38 mmol) and the reaction was warmed to 22° C. Next, the reaction mixture was extracted with CH2Cl2 (50 ml) and brine (25 ml). The combined organic layers were dried (MgSO4) and the crude product was purified by silica-gel chromatography (hexanes:EtOAc-50:50) to give the subtitle compound (204 mg, 68%). MS calculated for C13H17NO2S+H 252, observed 252.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[C:8]2[C:3]=1[C:4](=[N:29][S:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=[O:32])=[O:31])[CH:5]=[C:6]([C:13](=[O:28])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20]C(OC(C)(C)C)=O)[NH:7]2.FC(F)(F)C(O)=O>C(OCC)(=O)C>[Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[C:8]2[C:3]=1[C:4](=[N:29][S:30]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)(=[O:32])=[O:31])[CH:5]=[C:6]([C:13](=[O:28])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH2:20])[NH:7]2
Reactant: CC(C)(C)OC(=O)Nc1ccccc1C(=O)c1cc(=NS(=O)(=O)c2ccccc2)c2c(Cl)cc(Cl)cc2[nH]1
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Product: Nc1ccccc1C(=O)c1cc(=NS(=O)(=O)c2ccccc2)c2c(Cl)cc(Cl)cc2[nH]1
Reaction time: 24 h

Procedure:
Combine 5,7-dichloro-2-[2-(t-butoxycarbonylamino) benzoyl]-4-[benzenesulfonylimino]-1,4-dihydroquinoline (1 mmol) and ethyl acetate (50 mL). Add trifluoroacetic acid (1 mL) and stir. After 24 hours, evaporate in vacuo and partition the residue between dichloromethane and a saturated aqueous sodium bicarbonate solution. Separate the organic layer, dry over MgSO4, filter and evaporate in vacuo. Chromatograph the residue on a column of silica gel to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[CH:17]=[C:16]2[CH2:18][S:19][CH2:20][C:15]2=[N:14]1.C(Cl)Cl.C([O-])([O-])=[O:25].[Na+].[Na+]>>[Cl:12][C:4]1[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=[C:2]([Cl:1])[C:3]=1[N:13]1[CH:17]=[C:16]2[CH2:18][S:19](=[O:25])[CH2:20][C:15]2=[N:14]1
Reactant: FC(F)(F)c1cc(Cl)c(-n2cc3c(n2)CSC3)c(Cl)c1
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: O=S1Cc2cn(-c3c(Cl)cc(C(F)(F)F)cc3Cl)nc2C1
Temperature: -30 °C
Reaction time: 0.5 h
Yield: 60 %

Procedure:
To a solution of compound (3) (41 mg, 0.11 mmol) in CH2Cl2 (3 mL) m-CPBA (31.3 mg, 0.13 mmol) was added at −78° C. under N2. After 30 min. the reaction mixture was allowed to warm to −30° C. and stirred at −30° C. until the starting material disappeared completely. Aqueous Na2CO3 (10 mL) was then added and the organic phase was separated. The organic layer was washed with aq. Na2CO3 (10×4 mL), dried, concentrated to obtain a solid which was purified by flash chromatography on silica (20% EtOAc:hexane) to obtain the title compound (60%). 1H NMR (CDCl3) δ 7.78 (s, 2H), 7.45 (s, 1H), 7.53 (m, 2H), 4.01 (d, J=7.8 Hz, 1H), 3.88 (d, 7.8 Hz, 1H); MS (M+) 355.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH:11]([NH:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][CH:22]=1)[CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O1CCCC1.[OH-].[Na+]>C(O)C>[CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[CH:11]([NH:20][C:21]1[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:29][CH:30]=1)[CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: COC(=O)c1ccc(NC(COc2ccccc2)c2oc3ccccc3c2C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1c(C(COc2ccccc2)Nc2ccc(C(=O)O)cc2)oc2ccccc12
Reaction time: 8 h
Yield: 81.7 %

Procedure:
To a mixture of methyl 4-{[1-(3-methyl-1-benzofuran-2-yl)-2-phenoxyethyl]amino}benzoate (279 mg) synthesized above, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (5.00 mL), and the mixture was stirred overnight with heating under reflux, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (5.00 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (220 mg, 82%) as a white solid.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12]O)=[CH:2]1.C(Br)(Br)(Br)[Br:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)C>[Br:15][CH2:12][CH2:11][CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1
Reactant: BrC(Br)(Br)Br
Reactant: OCCCc1c[nH]c2ccccc12
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: BrCCCc1c[nH]c2ccccc12
Temperature: 0 °C
Reaction time: 3 h
Yield: 101.3 %

Procedure:
To a suspension of litium aluminum hydride (8.0 g) in tetrahydrofuran (500 mL) was a solution of 3-indolepropionic acid (20 g) in tetrahydrofuran (100 mL) added dropwise. The reaction mixture was stirred for 1 h at room temperature and subsequently cooled to 5° C. After sequential addition of water (16 mL), 15% aqueous sodium hydroxide (8.0 mL) and water (40 mL), the reaction mixture was stirred at room temperature over night and filtered. Evaporation of the volatile solvents gave pure 3-(1H-indol-3-yl)propanol (19.1 g) as an oil. 3-(1H-Indol-3-yl)propanol (18.6 g) and carbon tetrabromide (42.1 g) was dissolved in acetonitrile (1 L) and cooled to 0° C. and triphenylphosphine (30.7 g) was added in small portions. The reaction was stirred for further 3 h at room temperature, the volatile solvents evaporated in vacuo and the remaining oil purified by silicagel chromatography (heptane:ethyl acetate/2:1) to give 3-(3-bromopropyl)-1H-indole (25.6 g).
Reaction SMILES: [Cl:1]N1C(=O)CCC1=O.CSC.O[CH2:13]/[CH:14]=[C:15](/[CH3:22])\[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20]>ClCCl>[CH2:13]([Cl:1])/[CH:14]=[C:15](\[CH2:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])/[CH3:22]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CC(C)=CCC/C(C)=C\CO
Solvent: ClCCl
Solvent: CSC
Product: CC(C)=CCC/C(C)=C\CCl
Temperature: 0 °C
Reaction time: 4 h

Procedure:
To a solution of N-chlorosuccinimide (10.0 g) and dimethylsulfide (6.56 ml) in dichloromethane (200 ml) was added nerol (7.71 g) while being cooled with ice. The mixture was stirred at 0° C. for 4 hours. The reaction solution was washed with brine and dried over sodium sulfate anhydride. Then, the solvent was evaporated, thereby yielding a raw product of neryl chloride. In a manner similar to Reference Example 1, this raw product was reacted with methyl 4- hydroxybenzoate (7.61 g) and then hydrolyzed to yield 7.47 g (55%) of 4- neryloxybenzoic acid.
Reaction SMILES: O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:11][C:12]2[N:17]=[C:16]([N:18]3[C@@H:22]([CH:23]([CH3:25])[CH3:24])[CH2:21][O:20][C:19]3=[O:26])[CH:15]=[CH:14][N:13]=2)[CH3:10])=[CH:5][CH:4]=1.CS([Cl:31])(=O)=O.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:31][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:11][C:12]2[N:17]=[C:16]([N:18]3[C@@H:22]([CH:23]([CH3:25])[CH3:24])[CH2:21][O:20][C:19]3=[O:26])[CH:15]=[CH:14][N:13]=2)[CH3:10])=[CH:5][CH:4]=1
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(CO)cc2)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(CCl)cc2)n1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of (S)-3-(2-((S)-1-(4-(hydroxymethyl)phenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one (71 mg, 0.2 mmol) in DCM (2 mL) was added methanesulfonyl chloride (27 mg, 0.24 mmol) and DIPEA (0.070 mL, 0.4 mmol). The solution was stirred for 16 h at room temperature then washed with water and brine. After separation, the organic phase was dried over Na2SO4, filtered and concentrated. The crude product was used to next step without further purification.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][C:16](C)([O-])[CH3:17].[K+].C(I)(C)C>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH:16]([CH3:17])[CH3:15])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CC(C)I
Product: CC(C)C1CN(Cc2ccccc2)CCC1=O
Reaction time: 0.25 h

Procedure:
1-benzylpiperidin-4-one (10 g, 53.0 mmole) was added to the stirred suspension of potassium tert. butoxide (6.0 g, 54.0 mmole) in tetrahydrofuran (50 ml) at 10° C. The reaction mixture was stirred for 15 min, isopropyl iodide (10 g, 54.0 mmole) was added at 10° C. The resulting mixture allowed coming at room temperature and stirred for 16 hr, refluxed for 3 hr and concentrated to dryness. The residue was triturated with water, extracted with ethyl acetate, dried (Na2SO4) and concentrated to give crude product, which was purified through column chromatography. Elute from 10% ethyl acetate in hexane afforded 1-benzyl-3-isopropylpiperid-4-one. Yield 3.3 g (28%), C15H21NO, m/z 232 (M+1).