Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:15]2[NH:19][N:18]=[N:17][N:16]=2)[C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.CCN(CC)CC.[C:27](Cl)([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(Cl)Cl.CCOCC>[C:28]1([C:27]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:16]2[C:15]([C:4]3[C:5]([C:8]4[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=4)=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)=[N:19][N:18]=[N:17]2)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1ccc(-c2ccc(Cl)cc2-c2nnn[nH]2)cc1
Solvent: ClCCl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: Cc1ccc(-c2ccc(Cl)cc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Yield: 100 %

Procedure:
A solution of N-Triphenylmethyl-5-(4'-methyl-4-nitrobiphen-2-yl)tetrazole (0.115 g, 0.224 mmol) in MeOH/DMF (2 mL/12 mL) was submitted to hydrogenation at 40 psi H2 with 10% Pd on carbon (50 mg) at room temperature for 1 hour. The reaction was filtered through celite and the filtrate was concentrated in vacuo. The triphenyl methyl group had been lost during the hydrogenation. The crude 4-amino compound was dissolved in glacial acetic acid (3 mL) and added slowly to a cooled (0° C.) solution of NaNO2 (28.8 mg, 0.417 mmol) in conc. sulfuric acid (1 mL). The diazonium solution was stirred well for 2 hours then slowly added to a cooled (0° C.) solution of CuCl (0.449 g; 20 equiv) in conc. HCl. This mixture was stirred for 30 minutes and then poured over H2O and extracted with Et2O/EtOAc. The combined organic extracts were washed with H2O and brine, dried over MgSO4 and concentrated in vacuo. The product was purified by flash chromatography on a silica column eluting with Hex/EtOAc/HOAc (80:20;1) to afford 27 mg (45% for 2 steps) of 5-(4-chloro-4'-methyl-biphen-2-yl)tetrazole. The free tetrazole was dissolved in CH2Cl2 (3.5 mL) and NEt3 (0.035 mL, 2.5 equiv) and Ph3CCl (27 mg, 1.0 equiv) were added. After 30 minutes the reaction was diluted with Et2O washed with 10% citric acid, 1N NaOH and brine. The organic was dried over anhydrous MgSO4 and concentrated in vacuo to afford 51.2 mg (100%) of crude N-triphenylmethyl-5-(4-chloro-4'-methyl-biphen-2-yl)tetrazole. 1H NMR (300 MHz, CDCl3) δ2.26 (s, 3H), 6.91 (d, 6H), 6.94 (ABq, 4H), 7.20-7.25 (comp, 7H), 7.43 (dd, 1H), 7.99 (dd, 1H).
Reaction SMILES: [CH3:1][S:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]3[CH:15]=[C:16]([C:19]4[O:23][C:22]([SH:24])=[N:21][N:20]=4)[CH:17]=[CH:18][C:13]=3[O:12][CH:11]=2)=[CH:6][CH:5]=1)=[O:3].Br[CH2:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[C:30]#[N:31]>>[CH3:1][S:2]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[C:14]3[CH:15]=[C:16]([C:19]4[O:23][C:22]([S:24][CH2:26][C:27]5[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=5)[C:30]#[N:31])=[N:21][N:20]=4)[CH:17]=[CH:18][C:13]=3[O:12][CH:11]=2)=[CH:8][CH:9]=1)=[O:3]
Reactant: CS(=O)c1ccc(-c2coc3ccc(-c4nnc(S)o4)cc23)cc1
Reactant: N#Cc1cccc(CBr)c1
Product: CS(=O)c1ccc(-c2coc3ccc(-c4nnc(SCc5cccc(C#N)c5)o4)cc23)cc1
Yield: 76 %

Procedure:
In the same manner as in Example 7 and using 5-[3-[4-(methylsulfinyl)phenyl]-1-benzofuran-5-yl]-1,3,4-oxadiazole-2-thiol instead of 5-(1H-indazol-5-yl)-1,3,4-oxadiazole-2-thiol and 3-(bromomethyl)benzonitrile instead of 3-(trifluoromethyl)benzyl chloride, the title compound (yield 76%) was obtained as colorless crystals.
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][CH2:8][C:7](=[O:10])[N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:28]OS(C(F)(F)F)(=O)=O.Cl[C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39]>C1COCC1>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@:8]([CH3:28])([C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])[C:7](=[O:10])[N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]
Reactant: COC(=O)[C@@H]1CCC(=O)N1C(=O)OC(C)(C)C
Reactant: COS(=O)(=O)C(F)(F)F
Reactant: O=C(Cl)OCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)[C@@H]1C[C@@](C)(C(=O)OCc2ccccc2)C(=O)N1C(=O)OC(C)(C)C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 75 %

Procedure:
To a solution of (2S)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (6.0 g, 24.9 mmol) in THF (100 mL) at −78° C. was added LHMDS (1.0 M in THF, 27.13 mL). After 15 min stirring at −78° C., MeOTf (2.93 mL, 1.05 eq) was added slowly. The mixture was stirred at −78° C. for 30 min before a second portion of LHMDS (27.13 mL) was added. After 20 min stirring, benzyl chloroformate (4.42 mL, 1.25 eq) was added. The mixture was stirred at −78° C. for 2.0 h, and was quenched with 5% citric acid. Removal of solvent, extraction with EtOAC and column chromatography gave the product as a white solid (7.3 g, 75%). 1HNMR (300 MHz, CDCl3) δ 7.38 (m, 5H), 5.2 (m, 2H), 4.6 (m, 1H), 3.8 (s, 3H), 2.87 (dd, 1H, 13.6, 8.8 Hz), 1.88 (dd, 1H, J=13.6; 6.6 Hz), 1.6 (s, 3H), 1.5 (s, 9H).
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]([C@H:7]2[O:9][C@@H:8]2[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:5][CH:6]=1.[CH2:16]([O:20][CH2:21][CH2:22][CH2:23][NH2:24])[CH2:17][CH2:18][CH3:19].O>CC(C)=O>[CH2:16]([O:20][CH2:21][CH2:22][CH2:23][NH:24][CH:7]([C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1)[CH:8]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[OH:9])[CH2:17][CH2:18][CH3:19]
Reactant: c1ccc([C@H]2O[C@@H]2c2ccccc2)cc1
Reactant: CCCCOCCCN
Solvent: O
Solvent: CC(C)=O
Product: CCCCOCCCNC(c1ccccc1)C(O)c1ccccc1
Temperature: 140 °C
Reaction time: 18 h
Yield: 100 %

Procedure:
A mixture of trans-stilbene oxide (1.96 g, 0.010 mole) and 3-(n-butyloxy)-1-propylamine (3.93 g, 0.030 mole) was heated at 140° C. for 5 hrs. After standing at ambient temperature for 18 hr, the mixture was dissolved in acetone (20 ml) and the solution poured into water (120 ml). The solid which formed was collected by filtration and dried under ambient conditions to yield 3.24 g of slightly wet solid (>100%). Recrystallization from tolueneisooctane gave 1.70 g of a white solid, m.p. 82°-84° C.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]O)=[CH:4][C:3]=1[O:10][CH3:11].N1C=CC=CC=1.S(Cl)([Cl:20])=O>C1(C)C=CC=CC=1.O>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][Cl:20])=[CH:4][C:3]=1[O:10][CH3:11]
Reactant: O=S(Cl)Cl
Reactant: COc1cc(CO)ccc1Br
Solvent: O
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: COc1cc(CCl)ccc1Br

Procedure:
4-Bromo-3-methoxybenzyl alcohol (21.7 g, 0.1 m) dissolved in toluene (200 ml) containing pyridine (11.8 g, 0.15 m) is stirred at 5° and treated wiih thionyl chloride (23.8 g, 0.2 m). The mixture is stirred, diluted with water and the organic layer washed with dilute hydrochloric acid, dried and concentrated in vacuo to give 4-bromo-3-methoxybenzyl chloride.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([C:17]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:18])=[C:14]([CH3:25])[C:13]=2[CH:26]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].O>CO.O1CCCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([CH:17]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]3)[OH:18])=[C:14]([CH3:25])[C:13]=2[CH:26]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1c(C(=O)C2CCCCC2)oc2ccc(OCc3ccccc3)cc12
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: Cc1c(C(O)C2CCCCC2)oc2ccc(OCc3ccccc3)cc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 106.9 %

Procedure:
[5-(Benzyloxy)-3-methyl-1-benzofuran-2-yl](cyclohexyl)methanone (23.4 g) synthesized in Example A82(2) was dissolved in methanol (40 mL)-tetrahydrofuran (400 mL), and sodium tetrahydroborate (90%) (5.64 g) was added to the solution at 0° C. The reaction mixture was stirred at 0° C. for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated to give the title compound (25.17 g, 100%) as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH:21][C:22]([C:24]2[CH:25]=[CH:26][C:27]([CH2:30][N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[CH:28][CH:29]=2)=[O:23])=[CH:6][C:7]=1[NH:8][C:9]1[N:10]=[CH:11][CH:12]=[C:13]([C:15]2[CH:16]=[CH:17][CH:18]=[N:19][CH:20]=2)[N:14]=1.[C:38]([O:44][CH2:45][I:46])(=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40]>ClCCl>[I-:46].[CH3:37][N+:34]1([CH2:45][O:44][C:38](=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40])[CH2:33][CH2:32][N:31]([CH2:30][C:27]2[CH:28]=[CH:29][C:24]([C:22](=[O:23])[NH:21][C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[C:7]([NH:8][C:9]4[N:14]=[C:13]([C:15]5[CH:20]=[N:19][CH:18]=[CH:17][CH:16]=5)[CH:12]=[CH:11][N:10]=4)[CH:6]=3)=[CH:25][CH:26]=2)[CH2:36][CH2:35]1
Reactant: CC(C)(C)C(=O)OCI
Reactant: Cc1ccc(NC(=O)c2ccc(CN3CCN(C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1
Solvent: ClCCl
Product: Cc1ccc(NC(=O)c2ccc(CN3CC[N+](C)(COC(=O)C(C)(C)C)CC3)cc2)cc1Nc1nccc(-c2cccnc2)n1
Product: [I-]
Reaction time: 3.5 h
Yield: 27 %

Procedure:
Imatinib, N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide, [148] (0.100 g, 0.2 mmol, 1 eq) was dissolved in dichloromethane (10 ml) in a 25 ml two-necked round bottom flask, and iodomethyl pivalate [40] (0.049 g, 0.2 mmol, 1 eq) was added at RT. After stirring for 3-4 hours, the precipitate formed was filtered and washed with DCM to give the product, 1-methyl-4-(4-((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)carbamoyl)benzyl)-1-((pivaloyloxy)methyl)piperazin-1-ium iodide, [41] as a yellow solid. (0.040 g, 27% yield).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].[CH3:16][C:17]1([CH3:35])[C:28]2=[C:29]3[N:20]([CH2:21][CH2:22][C:23](C)([CH3:33])[C:24]3=[C:25](O)[C:26](C=O)=[CH:27]2)[CH2:19][CH2:18]1.N1CCCCC1>C(#N)C>[CH3:16][C:17]1([CH3:35])[C:28]2=[C:29]3[N:20]([CH2:21][CH2:22][C:23]([CH3:24])([CH3:33])[C:15]3=[C:14]3[O:13][C:11](=[O:12])[C:10]([C:2]4[S:1][C:5]5[C:4](=[CH:9][CH:8]=[CH:7][CH:6]=5)[N:3]=4)=[CH:25][C:26]3=[CH:27]2)[CH2:19][CH2:18]1
Reactant: CCOC(=O)Cc1nc2ccccc2s1
Reactant: CC1(C)CCN2CCC(C)(C)c3c(O)c(C=O)cc1c32
Solvent: CC#N
Solvent: C1CCNCC1
Product: CC1(C)CCN2CCC(C)(C)c3c2c1cc1cc(-c2nc4ccccc4s2)c(=O)oc31
Yield: 80.4 %

Procedure:
A mixture of 12.28 g of ethyl 2-(benzothiazolyl)acetate was refluxed with 15 g of 1,1,7,7-tetramethyl-8-hydroxy-9-formyljulolidine in 120 mL of acetonitrile containing 2 mL of piperidine as a base catalyst for 15 h. Upon cooling, the precipitated bright orange solid was filtered and washed with some acetonitrile to give 19 g (79% yield) of pure dye C-545T: m.p. 229-230° C.; Tg=100° C.
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([C:23]5[C:24](=[O:29])[NH:25][CH:26]=[CH:27][CH:28]=5)=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].I[CH:31]([CH3:33])[CH3:32]>>[CH:31]([N:25]1[CH:26]=[CH:27][CH:28]=[C:23]([C:20]2[CH:21]=[CH:22][C:15]3[O:14][CH2:13][CH2:12][C:11]4[S:10][C:9]([C:8]5[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][N:7]=5)=[N:18][C:17]=4[C:16]=3[CH:19]=2)[C:24]1=[O:29])([CH3:33])[CH3:32]
Reactant: CC(C)n1ncnc1-c1nc2c(s1)CCOc1ccc(-c3ccc[nH]c3=O)cc1-2
Reactant: CC(C)I
Product: CC(C)n1ncnc1-c1nc2c(s1)CCOc1ccc(-c3cccn(C(C)C)c3=O)cc1-2
Yield: 12 %

Procedure:
Following the procedure for 477, compound 330 and 2-iodopropane were reacted to give 489 (0.018 g, 12%). 1H NMR (400 MHz, DMSO) δ 9.06 (d, J=2.3, 1H), 8.20-8.01 (m, 1H), 7.77 (dd, J=6.9, 1.9, 1H), 7.62 (ddd, J=10.8, 7.7, 2.2, 2H), 7.08 (d, J=8.4, 1H), 6.41 (t, J=6.9, 1H), 6.11-5.79 (m, 1H), 5.20 (dt, J=13.8, 6.9, 1H), 4.55-4.22 (m, 2H), 3.46 (t, J=5.0, 2H), 1.56 (t, J=7.5, 6H), 1.36 (d, J=6.8, 6H). MS (ESI(+)): m/z 448.2 (M+H)
Reaction SMILES: [N+:1]([C:4]1[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=1[CH2:6][NH:7][CH2:8][CH2:9][CH2:10][OH:11])([O-:3])=[O:2].C(N(CC)CC)C.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.O>C(Cl)(Cl)Cl>[N+:1]([C:4]1[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=1[CH2:6][N:7]1[CH2:8][CH2:9][CH2:10][O:11][C:24]1=[O:26])([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccccc1CNCCCO
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: O=C1OCCCN1Cc1ccccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 63 %

Procedure:
3-(2-Nitrobenzylamino)-1-propanol (1.03 g, 4.90 mmol) was dissolved in chloroform (20 ml) and the reaction solution was cooled to 0° C. Then triethylamine (1.98 g, 19.6 mmol), triphosgene (0.58 g, 1.95 mmol) were added thereto and the mixture was stirred at the same temperature for 1.5 hours. The reaction mixture was added with water and extracted with ethyl acetate and after the organic layer was washed with a saturated brine, it was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:4) and 3-(2-nitrobenzyl)-[1,3]-oxazinan-2-one (0.29 g) was obtained.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:36]=[C:35]([F:37])[C:9]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([C:20]3[N:25]=[C:24]([NH:26][C:27]4[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=4)[C:23]([O:33][CH3:34])=[CH:22][N:21]=3)=[N:12]2)=[C:8]([F:38])[CH:7]=1)=[CH2:5])C.O.CC1C=CC(S(O)(=O)=O)=CC=1>C(O)C.O>[F:37][C:35]1[CH:36]=[C:6]([C:4](=[O:3])[CH3:5])[CH:7]=[C:8]([F:38])[C:9]=1[CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([C:20]2[N:25]=[C:24]([NH:26][C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)[C:23]([O:33][CH3:34])=[CH:22][N:21]=2)=[N:12]1
Reactant: C=C(OCC)c1cc(F)c(Cn2nc(-c3ncc(OC)c(Nc4ccncc4)n3)c3ccccc32)c(F)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Solvent: O
Product: COc1cnc(-c2nn(Cc3c(F)cc(C(C)=O)cc3F)c3ccccc23)nc1Nc1ccncc1
Temperature: 80 °C
Reaction time: 1 h

Procedure:
119 mg of 2-{1-[4-(1-ethoxyethenyl)-2,6-difluorobenzyl]-1H-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine (0.231 mmol, 1 eq.) and 66 mg of 4-methylbenzenesulfonic acid hydrate (1:1) (0.347 mmol, 1.5 eq.) were dissolved in 2.4 ml of ethanol and 0.6 ml of water. The mixture was stirred for one hour at 80° C. bath temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution. The phases were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography and preparative HPLC purification to yield 26 mg (0.05 mmol, 22.7%) of the analytically pure target compound.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:19]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]4[CH3:26])=[N:18][C:17]4[C:12](=[CH:13][CH:14]=[C:15]([C:27]([O:29]C)=[O:28])[CH:16]=4)[N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[Na+].O>CO.C(Cl)(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:19]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]4[CH3:26])=[N:18][C:17]4[C:12](=[CH:13][CH:14]=[C:15]([C:27]([OH:29])=[O:28])[CH:16]=4)[N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: COC(=O)c1ccc2nc(-c3ccc4[nH]ccc4c3)c(N3CCOC[C@@H]3C)nc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: O
Product: C[C@H]1COCCN1c1nc2cc(C(=O)O)ccc2nc1-c1ccc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.2 %

Procedure:
To a solution of (S)-methyl 2-(1H-indol-5-yl)-3-(3-methylmorpholino)quinoxaline-6-carboxylate (110 mg, 0.27 mmol) in methanol (15 mL) and CHCl3 (5 mL) was added NaOH (32.4 mg, 0.81 mmol) and water (1 mL). The resulting solution was stirred overnight at room temperature and concentrated in vacuo. The residue was dissolved in water (15 mL) and adjusted to pH 5 with hydrochloric acid (1N). The solids were collected by filtration to afford (S)-2-(1H-indol-5-yl)-3-(3-methylmorpholino)quinoxaline-6-carboxylic acid as a yellow solid (81 mg, 76%).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]1[N:22]=[C:15]2[C:16]([CH2:20][OH:21])=[CH:17][CH:18]=[CH:19][N:14]2[N:13]=1.C(N(CC)CC)C>ClCCl>[CH3:11][C:12]1[N:22]=[C:15]2[C:16]([CH:20]=[O:21])=[CH:17][CH:18]=[CH:19][N:14]2[N:13]=1
Reactant: Cc1nc2c(CO)cccn2n1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: Cc1nc2c(C=O)cccn2n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83613.3 %

Procedure:
Under nitrogen atmosphere, to a solution of oxalyl chloride (16.0 mL, 180 mmol) in dichloromethane (200 mL) was added dimethyl sulfoxide (30.0 mL, 0.420 mol) at −78° C., and the mixture was stirred for 30 min. To the reaction mixture was added a solution of (2-methyl[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (23.0 g, 0.141 mmol) in dichloromethane (82 mL), and the mixture was stirred for 2 hr. To the reaction mixture was added triethylamine (99.0 mL, 0.710 mol) at −78° C., and the mixture was stirred for 1 hr and warmed to room temperature. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (methanol/ethyl acetate=1/10) to give the title compound (19.0 g, yield 84%).
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[NH:13][C:12]([CH3:15])([CH3:14])[CH2:11][C:4]2([NH:8][C:7](=[O:9])[NH:6][C:5]2=[O:10])[CH2:3]1.[O:17]1[CH2:28][CH:18]1[CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH:25]1[O:27][CH2:26]1.[OH-:29].[K+]>CO>[OH:17][CH:18]([CH2:28][N:6]1[C:5](=[O:29])[C:4]2([CH2:3][C:2]([CH3:1])([CH3:16])[NH:13][C:12]([CH3:15])([CH3:14])[CH2:11]2)[NH:8][C:7]1=[O:9])[CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH:25]([OH:27])[CH2:26][N:6]1[C:5](=[O:10])[C:4]2([CH2:3][C:2]([CH3:16])([CH3:1])[NH:13][C:12]([CH3:15])([CH3:14])[CH2:11]2)[NH:8][C:7]1=[O:9]
Reactant: C(COCC1CO1)OCC1CO1
Reactant: CC1(C)CC2(CC(C)(C)N1)NC(=O)NC2=O
Reactant: [OH-]
Agent: [K+]
Solvent: CO
Product: CC1(C)CC2(CC(C)(C)N1)NC(=O)N(CC(O)COCCOCC(O)CN1C(=O)NC3(CC(C)(C)NC(C)(C)C3)C1=O)C2=O

Procedure:
A mixture of 7.7 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 2.5 g of ethylene glycol bis(2,3-epoxypropyl)ether and 0.1 g of potassium hydroxide in 80 ml of methanol was refluxed for 11 hours. Insoluble materials were then filtered off and the filtrate was washed with hot methanol. The solution was dried and then the solvent evaporated off. The residue was recrystallised from N,N-dimethylformamide, giving the desired compound in the form of white crystals, melting at 262°-264° C.
Reaction SMILES: [ClH:1].[CH2:2]([N:4]([CH2:35][CH3:36])[Si:5]1(N(CC)CC)[C:9]([Si:10]([CH3:13])([CH3:12])[CH3:11])=[C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:6]1[Si:26]([CH3:29])([CH3:28])[CH3:27])[CH3:3]>CCOCC>[Cl:1][Si:5]1([N:4]([CH2:35][CH3:36])[CH2:2][CH3:3])[C:9]([Si:10]([CH3:13])([CH3:12])[CH3:11])=[C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:6]1[Si:26]([CH3:29])([CH3:28])[CH3:27]
Reactant: CCN(CC)[Si]1(N(CC)CC)C([Si](C)(C)C)=C(c2ccccc2)C(c2ccccc2)=C1[Si](C)(C)C
Reactant: Cl
Solvent: CCOCC
Product: CCN(CC)[Si]1(Cl)C([Si](C)(C)C)=C(c2ccccc2)C(c2ccccc2)=C1[Si](C)(C)C
Reaction time: 20 h
Yield: 78 %

Procedure:
Dry hydrogen chloride gas was blown into a 100 ml ether solution of 4.17 g of 1,1-bis(diethylamino)-3,4-diphenyl-2,5-bis(trimethylsilyl)silole at -78° C. for one hour. After distilling ether off, dichloromethane was added, and then 1.3 ml of triethylamine and 1 ml of diethylamine were added in order. After continuing stirring at room temperatures for 20 hours, the solvent was distilled off, and dry hexane was added to remove insoluble matters by filtering. Then, hexane was distilled off from the filtrate to obtain a product. This product was refined by distillation to obtain 3.0 g of 1-chloro-1-diethylamino-3,4-diphenyl-2,5-bis(trimethylsilyl)silole. The yield was 78%.
Reaction SMILES: N1CCCCC1.[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[O:17][C:18]#[C:19][CH2:20][CH2:21][CH3:22])[CH:12]=O.C([CH2:26][C:27]([NH:29][C:30]1[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=1[C:32]([OH:34])=[O:33])=[O:28])(O)=O.Cl>C1(C)C=CC=CC=1>[CH3:7][O:8][C:9]1[CH:10]=[C:11](/[CH:12]=[CH:26]/[C:27]([NH:29][C:30]2[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=2[C:32]([OH:34])=[O:33])=[O:28])[CH:14]=[CH:15][C:16]=1[O:17][CH2:18][CH2:19][CH2:20][C:21]#[CH:22]
Reactant: O=C(O)CC(=O)Nc1ccccc1C(=O)O
Reactant: CCCC#COc1ccc(C=O)cc1OC
Agent: Cl
Solvent: C1CCNCC1
Solvent: Cc1ccccc1
Product: C#CCCCOc1ccc(/C=C/C(=O)Nc2ccccc2C(=O)O)cc1OC
Yield: 75.3 %

Procedure:
Piperidine (0.45 mL, 4.6 mmol) was added to a suspension of 3-methoxy-4-(pent-1-ynyloxy)benzaldehyde (1.0 g, 4.6 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (0.93 g, 4.2 mmol) in toluene (10 mL) and treated according to Procedure 2, acidifying with 1 M HCl. The crude product was recrystallised from EtOH/water providing (E)-2-[[3-(3-methoxy-4-(pent-4-ynyloxy)phenyl)-1-oxo-2-propenyl]amino]benzoic acid (1.2 g, 75%) as a pale yellow crystalline solid; mp 166.5-167.5° C.; δH (400 MHz, DMSO-d6) 1.89 (p, J=7.6 Hz, 2H, CH2), 2.32 (dt, J=7.6, 2.4 Hz, 2H, CH2CCH), 2.81 (t, J=2.4 Hz, 1H, CCH), 3.84 (s, 3H, OCH3), 4.06 (t, J=7.6 Hz, 2H, OCH2), 6.78 (d, J=15.6 Hz, 1H, CH═CHCO), 6.99 (d, J5′,6′=8.0 Hz, 1H, H5′), 7.17 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.22 (dd, J5′,6′=8.0, J2′,6′=2.0 Hz, 1H, H6′), 7.37 (d, J2′,6′=2.0 Hz, 1H, H2′), 7.55 (d, J=15.6 Hz, 1H, CH═CHCO), 7.60 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 8.00 (d, J3,4=8.0 Hz, 1H, H3), 8.62 (d, J5,6=8.0 Hz, 1H, H6), 11.27 (s, 1H, NH), 13.56 (br s, 1H, CO2H); δC (100 MHz, DMSO-d6) 14.5, 27.7, 55.7, 66.7, 71.7, 83.6, 110.7, 112.7, 116.6, 120.0, 120.3, 122.6, 122.7, 127.4, 131.1, 134.0, 141.1, 141.6, 149.2, 149.8, 164.1, 169.4; HRMS (ESI) calculated for C22H21NO5 [M+H]+ 380.1492. found 380.1493; vmax 755, 1257, 1506, 1584, 1657, 2929, 3266, 3519 cm−1.
Reaction SMILES: CO[C:3]([S:5]Cl)=O.S[CH:8]([OH:10])C.[SH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1>ClCCl>[N:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[S:11][S:5][CH2:3][CH2:8][OH:10]
Reactant: COC(=O)SCl
Reactant: CC(O)S
Reactant: Sc1ccccn1
Solvent: ClCCl
Product: OCCSSc1ccccn1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 114.6 %

Procedure:
To a solution of methoxycarbonyl sulfenyl chloride (10 mL, 110 mmol), in dichloromethane (100 mL), cooled to 0° C., was added mercaptoethanol (7.6 mL, 110 mmol), dropwise. The reaction mixture was allowed to stir at 0° C. for 30 min. At this point, a solution of 2-mercaptopyridine (12.2 g, 110 mmol) in dichloromethane (160 mL) was added. The solution was allowed to react at 0° C. for 1 hr and then was allowed to warm to RT for another 1 hr. Solid product was observed to have fallen out of solution. TLC (1:1 Pet Ether/EtOAc) showed that significant product had been formed. The reaction mixture was concentrated to a volume of 125 mL. The mixture was filtered through a Buchner funnel The filter cake was washed with dichloromethane and then dried under vacuum overnight to afford 2-(2-(Pyridin-2-yl)disulfanyl)ethanol (23.6 g), as the HCl salt.