Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH2:8][CH2:9][C:10](=[O:16])[NH:11]2.[CH:17]1[CH:18]=[CH:19][C:20]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:21][CH:22]=1.C1(C)C=CC=CC=1.CCCCCC>C(Cl)(Cl)Cl>[ClH:1].[C:20]1([N:23]2[CH2:28][CH2:27][N:26]([CH2:2][CH2:3][CH2:4][O:5][C:6]3[CH:15]=[CH:14][CH:13]=[C:12]4[C:7]=3[CH2:8][CH2:9][C:10](=[O:16])[NH:11]4)[CH2:25][CH2:24]2)[CH:21]=[CH:22][CH:17]=[CH:18][CH:19]=1
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: O=C1CCc2c(cccc2OCCCCl)N1
Solvent: ClC(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: Cl
Product: O=C1CCc2c(cccc2OCCCN2CCN(c3ccccc3)CC2)N1

Procedure:
4.8 Grams of 5-(3-chloropropoxy)-3,4-dihydrocarbostyril and 4 g of phenylpiperazine are mixed with 40 ml of toluene and heated for 24 hours under refluxing condition. Then the reaction mixture is concentrated under reduced pressure to dryness. The residue thus obtained is dissolved in 80 ml of chloroform and the chloroform layer is washed twice with 5.0% of sodium hydrogencarbonate aqueous solution, further washed twice with water, dried with anhydrous sodium sulfate and chloroform is removed by distillation. To the residue thus obtained is added hexane and the insoluble material is collected by filtration and then dissolved in 30 ml of 5% HCl-methanol solution and concentrated under reduced pressure to dryness. The residue obtained is recrystallized from methanol-ether to obtain 3.2 g of 5-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril monohydrochloride in the form of colorless crystals with a melting point of 262° C. (decomposition).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]([OH:10])=O)[CH2:3][CH2:2]1.CCN=C=NCCCN(C)C.Cl.[F:23][C:24]([F:66])([F:65])[C:25]1[CH:26]=[C:27]([CH:62]=[CH:63][CH:64]=1)[CH2:28][NH:29][C:30](=[O:61])[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([C:37]2[CH:42]=[C:41]([N:43]3[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)[CH:40]=[CH:39][C:38]=2[NH:49][C:50](=[O:60])[C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([CH2:57][NH:58][CH3:59])[CH:52]=2)[CH:32]=1>ClCCl.CN(C)C1C=CN=CC=1>[CH3:59][N:58]([CH2:57][C:53]1[CH:52]=[C:51]([CH:56]=[CH:55][CH:54]=1)[C:50]([NH:49][C:38]1[CH:39]=[CH:40][C:41]([N:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)=[CH:42][C:37]=1[C:33]1[CH:32]=[C:31]([CH:36]=[CH:35][N:34]=1)[C:30]([NH:29][CH2:28][C:27]1[CH:62]=[CH:63][CH:64]=[C:25]([C:24]([F:65])([F:23])[F:66])[CH:26]=1)=[O:61])=[O:60])[C:8](=[O:10])[CH2:7][N:4]1[CH2:3][CH2:2][O:1][CH2:6][CH2:5]1
Reactant: CNCc1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Reactant: O=C(O)CN1CCOCC1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CN(Cc1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1)C(=O)CN1CCOCC1
Temperature: 25 °C
Reaction time: 6 h
Yield: 38.3 %

Procedure:
Into a 50-mL round-bottom flask, was placed a solution of 2-morpholinoacetic acid (25.0 mg, 0.17 mmol, 1.00 equiv) in dichloromethane (10 mL), EDC.HCl (50.0 mg, 0.26 mmol, 1.50 equiv), 4-dimethylaminopyridine (32.0 mg, 0.26 mmol, 1.50 equiv), and N-(3-(trifluoromethyl)benzyl)-2-(2-(3-((methylamino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide (1000 mg, 1.66 mmol, 1.00 equiv). The resulting solution was stirred for 6 h at 25° C. in an oil bath. The resulting solution was diluted with 50 mL of dichloromethane. The resulting mixture was washed with 2×30 mL of aqueous NH4Cl. The resulting mixture was washed with brine. The mixture was dried over sodium sulfate and concentrated under vacuum. The crude product (120 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 47.4 mg (26%) of a pale-yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.90-8.98 (m, 1H), 8.57-8.64 (m, 1H), 8.40 (s, 1H), 7.84-8.00 (m, 4H), 7.54-7.72 (m, 7H), 4.72-4.76 (m, 4H), 4.36-4.38 (m, 2H), 3.96 (m, 4H), 3.58-3.61 (m, 4H), 3.01 (s, 3H), 1.99-2.00 (m, 4H), 1.75 (m, 2H). MS (ES, m/z) 729 [M+H]+.
Reaction SMILES: [CH:1]([NH:3][CH2:4][C:5]1[N:12]2[C:8]([S:9][CH:10]=[CH:11]2)=[CH:7][N:6]=1)=[O:2].C([Li])CCC.CCCCCC.[CH2:24]([Sn:28](Cl)([CH2:33][CH2:34][CH2:35][CH3:36])[CH2:29][CH2:30][CH2:31][CH3:32])[CH2:25][CH2:26][CH3:27].[Cl-].[NH4+]>CN(P(N(C)C)(N(C)C)=O)C.C1COCC1>[CH:1]([NH:3][CH2:4][C:5]1[N:12]2[C:8]([S:9][C:10]([Sn:28]([CH2:29][CH2:30][CH2:31][CH3:32])([CH2:33][CH2:34][CH2:35][CH3:36])[CH2:24][CH2:25][CH2:26][CH3:27])=[CH:11]2)=[CH:7][N:6]=1)=[O:2]
Reactant: O=CNCc1ncc2sccn12
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1cn2c(CNC=O)ncc2s1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 9 06 mg of 5-formylaminomethyl imidazo[5,1-b]-thiazole in a mixed solvent of 30 ml of THF and 6 ml of HMPA was cooled to −78° C. under the atmosphere of argon, and 10.9 ml of a 1.6 N solution of n-butyl lithium/n-hexane was added dropwise at an internal temperature of −70-−65° C. After the reaction mixture was stirred at the same temperature for 1 hour, 1.63 ml of tri-n-butylstannyl chloride was added, and the mixture was further stirred at the same temperature for 1 hour and for 2 hours during which the temperature was raised up to 0° C. 100 ml of a semi-saturated aqueous ammonium chloride solution was added to the reaction mixture, and extracted with 100 ml of diethyl ether. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by column chromatography on silica gel (hexane:ethyl acetate=1:2) to give the title compound in an amount of 1.59 g.
Reaction SMILES: [CH:1]1([C:6]([C:9]2[C:21]3[CH2:20][C:19]4[C:14](=[CH:15][C:16]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][CH:18]=4)[C:13]=3[CH:12]=[C:11]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:10]=2)([CH3:8])[CH3:7])[CH:5]=[CH:4][CH:3]=[CH:2]1.[Li]CCCC.Cl[Si:36]([CH3:39])([CH3:38])[CH3:37]>C1COCC1>[CH3:37][Si:36]([CH3:39])([CH3:38])[C:3]1[CH:4]=[CH:5][CH:1]([C:6]([C:9]2[C:21]3[CH2:20][C:19]4[C:14](=[CH:15][C:16]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][CH:18]=4)[C:13]=3[CH:12]=[C:11]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:10]=2)([CH3:8])[CH3:7])[CH:2]=1
Reactant: CC(C)(C)c1ccc2c(c1)-c1cc(C(C)(C)C)cc(C(C)(C)C3C=CC=C3)c1C2
Reactant: C[Si](C)(C)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(C)c1ccc2c(c1)-c1cc(C(C)(C)C)cc(C(C)(C)C3C=CC([Si](C)(C)C)=C3)c1C2
Yield: 84.3 %

Procedure:
In a 50 ml Schlenk flask purged with nitrogen, 1.44 g (3.74 mmol, 1 eq) of 2-(cyclopentadienyl)-2-(3,6-di-tert-butylfluorenyl)propane was placed at room temperature. Then, 20 ml of dehydrated THF was added, and the mixture was stirred by a magnetic stirrer to give a solution. The solution was cooled with an ice bath (light yellowish orange solution). To the solution, 2.5 ml (1.63 mmol, 1.09 eq) of n-BuLi (hexane solution) was dropwise added. The ice bath was removed, and the solution was stirred at room temperature for 19 hours (dark red solution). The solution was cooled with an ice bath, and to the solution, 2.7 ml (21.3 mmol, 5.70 eq) of chlorotrimethylsilane was dropwise added by a syringe. The ice bath was removed, and the solution was stirred at room temperature for 3 hours. The resulting yellow solution was poured into 80 ml of a diluted hydrochloric acid solution to perform quenching. After the soluble component was extracted with 100 ml of diethyl ether, the organic phase was washed with 50 ml of a saturated saline solution. The organic phase was dried over MgSO4, then the MgSO4 was filtered off, and from the filtrate the solvent was vacuum distilled off by a rotary evaporator to obtain a light yellow solid. The solid was washed with 50 ml of methanol and vacuum dried to obtain 1.44 g a light creamy powder (yield: 84%)
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1([C:13]([OH:15])=O)[CH2:12][CH2:11]1.C(Cl)(=O)C(Cl)=O.[Br-].O[C:24]1[CH:49]=[CH:48][CH:47]=[CH:46][C:25]=1[CH2:26][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1([C:13]2[O:15][C:24]3[CH:49]=[CH:48][CH:47]=[CH:46][C:25]=3[CH:26]=2)[CH2:11][CH2:12]1
Reactant: COc1ccc(Br)c(C2(C(=O)O)CC2)c1
Reactant: Oc1ccccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C(Cl)C(=O)Cl
Agent: [Br-]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1ccc(Br)c(C2(c3cc4ccccc4o3)CC2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 81.8 %

Procedure:
To the DCM solution (6 ml) of 1-(2-bromo-5-methoxy-phenyl)-cyclopropane carboxylic acid (0.3 g, 1.1 mmol), DMF (2 drops) and oxalyl chloride (0.23 ml, 2.5 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2 hrs. The residues obtained from the reaction solution after concentration under reduced pressure were dissolved in toluene (6 ml), added with (2-hydroxybenzyl)triphenylphosphonium bromide (0.605 g, 1.32 mmol) and TEA (0.46 ml, 3.3 mmol), and the resulting mixture was stirred and heated at 100° C. overnight. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:DCM) to obtain the title compound (0.309 g, 81%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH:26]=[CH2:27])=[C:4]([CH:9]=[C:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH:25]=[CH:24][CH:23]=[N:22]3)=[CH:17][CH:16]=2)[C:11]=1[O:12][CH3:13])[C:5]([O:7]C)=[O:6].O.O.[OH-].[Li+].Cl>C1COCC1.CO>[Cl:1][C:2]1[C:3]([CH:26]=[CH2:27])=[C:4]([CH:9]=[C:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH:25]=[CH:24][CH:23]=[N:22]3)=[CH:17][CH:16]=2)[C:11]=1[O:12][CH3:13])[C:5]([OH:7])=[O:6]
Reactant: C=Cc1c(C(=O)OC)cc(Cc2ccc(-n3cccn3)cc2)c(OC)c1Cl
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: C=Cc1c(C(=O)O)cc(Cc2ccc(-n3cccn3)cc2)c(OC)c1Cl
Temperature: 20 °C
Reaction time: 16 h
Yield: 83 %

Procedure:
To a solution of methyl 3-chloro-2-ethenyl-4-methoxy-5-[4-(1H-pyrazol-1-yl)benzyl]benzoate (0.10 g) in THF (3.00 mL)-water (3.00 mL) and methanol (0.50 mL) was added lithium hydroxide monohydrate (0.10 g), and the mixture was stirred at 20° C. for 16 hr. The reaction mixture was poured into 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (0.08 g).
Reaction SMILES: [CH2:1]([N:3]([CH2:37][CH3:38])[CH2:4][CH2:5][CH2:6][NH:7][C:8]1[N:9]=[C:10]([C:27]2[CH:28]=[C:29]([CH:33]=[CH:34][C:35]=2[CH3:36])[C:30]([OH:32])=O)[C:11]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:12]=2[N:13]=1)[CH3:2].CN(C(O[N:47]1N=N[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:48]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C1(N)CCCCC1>CN(C=O)C>[CH:48]1([NH:47][C:30](=[O:32])[C:29]2[CH:33]=[CH:34][C:35]([CH3:36])=[C:27]([C:10]3[C:11]4[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]5[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=5[F:25])[C:12]=4[N:13]=[C:8]([NH:7][CH2:6][CH2:5][CH2:4][N:3]([CH2:37][CH3:38])[CH2:1][CH3:2])[N:9]=3)[CH:28]=2)[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]1
Reactant: CCN(CC)CCCNc1nc(-c2cc(C(=O)O)ccc2C)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: NC1CCCCC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCN(CC)CCCNc1nc(-c2cc(C(=O)NC3CCCCC3)ccc2C)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 29.9 %

Procedure:
To the compound 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylbenzoic acid (26 mg, 0.05 mmol) in DMF (0.5 mL) were added HBTU (28 mg, 0.075 mmol), triethylamine (21.1 uL, 0.15 mmol) and cyclohexanamine (11.5 uL, 0.1 mmol). The mixture was stirred at rt overnight. Separation by HPLC with TFA, followed by neutralization with SPE amine cartridge afforded the title compound (9 mg, 30%). LC-MS m/z 603 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C:16](=O)[CH3:17].C([O-])(=O)C.[NH4+].C([BH3-])#[N:25].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[CH:16]([NH2:25])[CH3:17]
Reactant: [BH3-]C#N
Reactant: CC(=O)c1ccc(F)cc1-c1cc(F)ccc1F
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: CC(N)c1ccc(F)cc1-c1cc(F)ccc1F

Procedure:
The title compound was prepared from 1-(2′,5′,5-trifluoro-1,1′-biphenyl-2-yl)ethanone (650 mg, 2.6 mmol), anhydrous methanol (10 mL), ammonium acetate (4.0 g, 52 mmol), and sodium cyanoborohydride (326 g, 5.2 mmol) according to the procedure and in the same manner as described in Example 105, step b. The crude amine was immediately used without further purification in Example 116, step c;
Reaction SMILES: [NH2:1][C:2]([P:9]([OH:12])(=[O:11])[OH:10])([P:5]([OH:8])(=[O:7])[OH:6])[CH2:3][CH3:4].[OH-].[Na+].[C:15]([OH:20])(=[O:19])/[CH:16]=[CH:17]/[CH3:18].Cl>O>[C:15]([CH:16]([NH:1][C:2]([P:5]([OH:8])(=[O:6])[OH:7])([P:9]([OH:12])(=[O:10])[OH:11])[CH2:3][CH3:4])[CH2:17][CH3:18])([OH:20])=[O:19]
Reactant: CCC(N)(P(=O)(O)O)P(=O)(O)O
Reactant: C/C=C/C(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCC(NC(CC)(P(=O)(O)O)P(=O)(O)O)C(=O)O
Temperature: 100 °C

Procedure:
54.8 g. of 1-amino propane-1,1-diphosphonic acid and 40 g. of sodium hydroxide are dissolved in 150 cc. of water. 10 g. of sodium hydroxide dissolved in 40 cc. of water and 22 g. of crotonic acid dissolved in 50 cc. of water are added drop by drop simultaneously thereto while stirring vigorously. After continuing stirring for one hour, the temperature of the reaction mixture is increased to 100° C. and the reaction solution is boiled under reflux for 3 hours. It is then slightly acidified with hydrochloric acid. Any turbidity occurring thereby is removed by filtration. After treating the solution with an acid ion exchange agent, the N-(1-carboxy propyl)-1-amino propane-1,1-diphosphonic acid is obtained as an oily residue. This residue is mixed with 100 cc. of ethanol, the ethanol is decanted, and the residue is dried.
Reaction SMILES: [Pb]=[O:2].S(=O)(=O)(O)O.S([O-])([O-])(=O)=O.[Na+].[Na+].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1>O>[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]=[O:2])=[CH:19][CH:18]=1
Reactant: COc1ccc(C)cc1
Reactant: O=[Pb]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Product: COc1ccc(C=O)cc1
Reaction time: 3.33 h
Yield: 46 %

Procedure:
In this example a divided electrochemical cell provided with a lead oxide anode and cathode and an anion exchange membrane sold under the tradename IONAC 3475 was used. The anolyte was prepared by admixing 25 grams of sulfuric acid with 250 grams of water and thereafter adding 100 grams of manganous sulfate. The catholyte was prepared by adding 25 grams of sulfuric acid to 250 grams of water and thereafter adding 30 grams of sodium sulfate. The anolyte solution and catholyte solution were added to the respective reservoirs and thereafter 50 grams of p-methoxytoluene was slowly added to the anolyte solution. The electrical energy which was used consisted of an E applied voltage ranging from 4.0 to 6.0 volts along with about 2.0 amps while maintaining the current density at a rate of about 80 milliamps/cm2. In addition, the reaction was run at ambient temperature and atmospheric pressure. The solution was passed through the cell and condenser and back to the cell by use of a pump. The reaction was run for a period of 3.33 hours at the end of which time a gas liquid chromatographic analysis disclosed a yield of 46% anisaldehyde with a selectivity to the aldehyde of greater than 50%, current efficiencies of 85-100% being observed.
Reaction SMILES: [NH2:1][N:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:18].[CH3:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][C:27](O)=[O:28]>>[CH3:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][C:27]([NH:1][N:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:18])=[O:28]
Reactant: Nn1nc(N2CCOCC2)c2ccccc2c1=O
Reactant: Cc1ccccc1CC(=O)O
Product: Cc1ccccc1CC(=O)Nn1nc(N2CCOCC2)c2ccccc2c1=O

Procedure:
The product of Example 1B and 2-(2-methylphenyl)acetic acid were treated using a method similar to that described in Example 111 to give the title compound. 1H NMR (500 MHz, DMSO-d6/D2O) δ 8.31 (d, J=7.8, 1H), 8.03 (d, J=7.7, 1H), 8.01-7.96 (m, 1H), 7.94-7.87 (m, 1H), 7.33-7.30 (m, 1H), 7.24-7.14 (m, 3H), 3.84-3.81 (m, 4H), 3.68 (s, 2H), 3.15-3.06 (m, 4H), 2.35 (s, 3H); MS (ESI+) M/Z 379 (M+H)+.
Reaction SMILES: [CH2:1]([NH:4][CH:5]1[CH2:13][CH2:12][C:8]2[N:9]=[CH:10][S:11][C:7]=2[CH2:6]1)CC.O=[CH:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]1[S:26][C:25]2[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=2[CH:23]=1)=[O:21]>>[CH3:1][N:4]([CH:5]1[CH2:13][CH2:12][C:8]2[N:9]=[CH:10][S:11][C:7]=2[CH2:6]1)[CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]1[S:26][C:25]2[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=2[CH:23]=1)=[O:21]
Reactant: O=CCCCNC(=O)c1cc2ccccc2s1
Reactant: CCCNC1CCc2ncsc2C1
Product: CN(CCCCNC(=O)c1cc2ccccc2s1)C1CCc2ncsc2C1
Yield: 58 %

Procedure:
Compound 11 is prepared as described for 1 from 1C and 11A. The salt of oxalic acid is crystallized from ethanol/diethylether.
Reaction SMILES: [CH2:1]([C:4]1([CH:20]([CH3:22])[CH3:21])[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].B.C1C[O:27]CC1>C1COCC1>[Br:19][C:16]1[CH:15]=[CH:14][C:13]([C@@H:11]([N:7]2[CH2:6][CH2:5][C:4]([CH2:1][CH2:2][CH2:3][OH:27])([CH:20]([CH3:22])[CH3:21])[O:9][C:8]2=[O:10])[CH3:12])=[CH:18][CH:17]=1
Reactant: C1CCOC1
Reactant: C=CCC1(C(C)C)CCN([C@@H](C)c2ccc(Br)cc2)C(=O)O1
Agent: B
Product: CC(C)C1(CCCO)CCN([C@@H](C)c2ccc(Br)cc2)C(=O)O1
Reaction time: 2 h
Yield: 22 %

Procedure:
To a solution of 6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-isopropyl-1,3-oxazinan-2-one (480 mg, 1.315 mmol) in THF (5 mL) was added BH3.THF (5.3 mL, 5.3 mmol) at 0° C. under N2. The reaction mixture was stirred for 2 h, and quenched with water, 3 M aq NaOH (1 mL), and H2O2 (5 mL). The resulting mixture was stirred for 2 h, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by prep TLC to give 3-((S)-1-(4-bromophenyl)ethyl)-6-(3-hydroxypropyl)-6-isopropyl-1,3-oxazinan-2-one. (110 mg, 22% yield). 1H NMR (CDCl3): δ0.88 (m, 6H), 1.45 (m, 3H), 1.60 (m, 4H), 1.71 (m, 1H), 1.82 (m, 1H), 1.99 (m, 1H), 2.63 (m, 1H), 3.03 (m, 1H), 3.59 (m, 2H), 5.68 (m, 1H), 7.13 (d, 2H), 7.40 (d, 2H),
Reaction SMILES: C1(S[CH2:8][C:9]([NH:11][NH:12][C:13]([N:15]2[CH2:21][C:20]3[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=3[O:18][C:17]3[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:16]2=3)=[O:14])=[O:10])C=CC=CC=1.Cl[C:32]1[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=1)C(OO)=O.[S:42]([O-:46])([O-])(=[O:44])=S.[Na+].[Na+]>ClCCl>[C:32]1([S:42]([CH2:8][C:9]([NH:11][NH:12][C:13]([N:15]2[CH2:21][C:20]3[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=3[O:18][C:17]3[CH:26]=[CH:27][C:28]([Cl:30])=[CH:29][C:16]2=3)=[O:14])=[O:10])(=[O:46])=[O:44])[CH:33]=[CH:34][CH:39]=[CH:40][CH:41]=1
Reactant: O=S([O-])([O-])=S
Reactant: O=C(CSc1ccccc1)NNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: O=C(CS(=O)(=O)c1ccccc1)NNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21

Procedure:
To a stirred solution of 2.0 g (4.5 mmole) of the title product of Example 2 in 40 ml of cold (ca. 0° ) dichloromethane was added 1.94 g (9.1 mmole) of 81% m-chloroperoxybenzoic acid. After about ninety minutes, 10 ml of saturated aqueous sodium thiosulfate was added. The mixture was washed sequentially with three portions of saturated aqueous sodium bicarbonate and three portions of water. The organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo to give the title compound, m.p. 180°-183°.
Reaction SMILES: [CH:1]1([C:6]2[CH:11]=[CH:10][C:9]([NH2:12])=[C:8]([CH3:13])[C:7]=2[NH2:14])[CH2:5][CH2:4][CH:3]=[CH:2]1.[OH-].[K+]>C(O)(C)C>[C:1]1([C:6]2[CH:11]=[CH:10][C:9]([NH2:12])=[C:8]([CH3:13])[C:7]=2[NH2:14])[CH2:5][CH2:4][CH2:3][CH:2]=1
Reactant: Cc1c(N)ccc(C2C=CCC2)c1N
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Product: Cc1c(N)ccc(C2=CCCC2)c1N
Temperature: 160 °C

Procedure:
A 15.0g (72.61 mmol) portion of 3-(cyclopent-2-enyl)-2,6-toluenediamine was added to a 250cc round bottomed flask containing 1.50g (22.7 mmol) of 85% potassium hydroxide, 16.79 (278.0 mmol) isopropanol, 100cc of mixed xylenes. The mixture was stirred at room temperature under a static nitrogen atmosphere until all the potassium hydroxide had dissolved. The flask was fitted with a Claisen distillation head, a condenser, a receiving flask and then warmed to 115°. Isopropanol and water were removed over a 2 hour period. The temperature of the reaction flask was then raised to 160° C. and maintained for a period of 5 hours. During this period, the mixed xylenes were slowly removed by atmospheric distillation. The product was then isolated from the flask by bulb-to-bulb distillation at 160°-180° C. 10.5mm Hg. An 11.5g sample (76.7% isolated yield) of the α-β-unsaturated product was obtained.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[NH2:13][C:14]1[C:19]2[C:20]([C:28]3[CH:29]=[N:30][C:31]4[C:36]([CH:37]=3)=[CH:35][CH:34]=[CH:33][CH:32]=4)=[C:21]3[N:26]([C:18]=2[N:17]=[CH:16][N:15]=1)[CH2:25][CH:24]([OH:27])[CH2:23][CH2:22]3.C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:8][S:9]([O:27][CH:24]1[CH2:23][CH2:22][C:21]2[N:26]([C:18]3[N:17]=[CH:16][N:15]=[C:14]([NH2:13])[C:19]=3[C:20]=2[C:28]2[CH:29]=[N:30][C:31]3[C:36]([CH:37]=2)=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:25]1)(=[O:11])=[O:10]
Reactant: Nc1ncnc2c1c(-c1cnc3ccccc3c1)c1n2CC(O)CC1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OC1CCc2c(-c3cnc4ccccc4c3)c3c(N)ncnc3n2C1
Reaction time: 0.25 h

Procedure:
Triethylamine (0.157 ml) and methanesulfonyl chloride (0.074 ml) were added to a solution of 4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-ol (288 mg) obtained in Step 8 in THF (5 ml) under ice-cooling. After stirring at the same temperature for 15 minutes, the mixture was poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound as a light-brown solid (615 mg).