Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([Cl:25])[C:16]=1[O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])C=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].ClC1C=CC=C([C:33]([O:35]O)=[O:34])C=1>ClCCl.O>[CH:33]([O:35][C:11]1[CH:14]=[C:15]([Cl:25])[C:16]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:19])[CH3:20])=[C:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:2])[CH3:3])[CH:10]=1)=[O:34]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(C)(C)[Si](C)(C)Oc1cc(C=O)cc(Cl)c1O[Si](C)(C)C(C)(C)C
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)[Si](C)(C)Oc1cc(OC=O)cc(Cl)c1O[Si](C)(C)C(C)(C)C
Yield: 69.1 %

Procedure:
To a solution of 1.73 g (4.30 mmol) of 13 in 15 mL of dichloromethane under argon was added 2.03 g (6.50 mmol) of 55% m-chloroperbenzoic acid (MCPBA). After refluxing for 10 h, the solution was diluted with 30 mL of water and extracted three times with diethyl ether (50 mL each). The combined extracts were washed twice with saturated aqueous NaHCO3 (30 mL each), 30 mL of water, and 30 mL of brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using hexane as eluent to give 1.24 g (70% yield) of 3,4-bis-(t-butyldimethylsilyloxy)-5-chlorophenyl formate. 1H NMR (CDCl3) δ 8.22 (s, 1H, CHO), 6.79 (d,J=3.2 Hz, 1H), 6.58 (d,J=3.2 Hz, 1H), 1.03 (s, 9H, t-Bu), 0.96 (s, 9H, t-Bu), 0.22 (s, 6H, Me), 0.19 (s, 6H, Me); 13C NMR (CDCl3) δ 159.0 (s, C═O), 148.8 (s), 143.0 (s), 142.4 (s), 127.1 (s), 115.5 (d), 113.1 (d), 26.2 (q, 6C, t-Bu), 18.8 (s, 2C, t-Bu), −3.3 (q, 2C, Me), −3.6 (q, 2C, Me).
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[N:6][CH:7]=[C:8]3[C:13]=2[CH:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=[CH:3][CH:2]=1.[CH:15]1([C:21](Cl)=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.[NH:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25]1>>[CH:15]1([C:21]([N:6]2[CH:7]([C:26]3[C:27]4[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=4)[NH:24][CH:25]=3)[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]2=3)=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: c1ccc2c(c1)cnc1ccccc12
Reactant: O=C(Cl)C1CCCCC1
Reactant: c1ccc2[nH]ccc2c1
Product: O=C(C1CCCCC1)N1c2ccccc2-c2ccccc2C1c1c[nH]c2ccccc12

Procedure:
Cyclohexyl-[6-(1H-indol-3-yl)-6H-phenanthridin-5-yl]-methanone was prepared from phenanthridine, cyclohexanecarboxylic acid chloride, and indole according to GP 2. Yield, 7%. (+)-ESI-MS: m/z=407 [M+H]+, 290 [M-indole+H]+, 180.
Reaction SMILES: [Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:46])[C:5]([C:34]([O:36]CC1C=CC(OC)=CC=1)=[O:35])=[CH:6][N:7]2[CH2:32][CH3:33].[OH-].[K+]>CO.O>[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:46])[C:5]([C:34]([OH:36])=[O:35])=[CH:6][N:7]2[CH2:32][CH3:33]
Reactant: CCn1cc(C(=O)OCc2ccc(OC)cc2)c(=O)c2c(Cl)c(OCc3ccc(OC)cc3)c(OCc3ccc(OC)cc3)cc21
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCn1cc(C(=O)O)c(=O)c2c(Cl)c(OCc3ccc(OC)cc3)c(OCc3ccc(OC)cc3)cc21
Temperature: 25 °C
Yield: 98.1 %

Procedure:
To a suspension of 4-methoxybenzyl 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylate (8.4 g, 13.04 mmol) in a mixture of Methanol (90 mL) and Water (30.0 mL) was added KOH (1.463 g, 26.1 mmol) portionwise. The resulting mixture was stirred under reflux for 1.5 h. The mixture was then cooled down to r.t., concentrated, diluted with water (150 mL) and adjusted pH to 2-3 using 6 N HCl (aq.). The precipitates were collected by filtration and dried to afford 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (6.7 g, 12.79 mmol, 98% yield) as a white solid. LCMS: (M+H)+: 524.2.
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:4][CH2:3]1.[C:15]([BH3-])#[N:16].[Na+].[C:19](O)(=O)[CH3:20].Cl>C(O)C>[CH2:15]([NH:16][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:4][CH2:3]1)[C:20]1[CH:19]=[CH:4][CH:3]=[CH:2][CH:7]=1
Reactant: [BH3-]C#N
Reactant: CC(=O)O
Reactant: CCOC(=O)CCN1CCC(=O)CC1
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)CCN1CCC(NCc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 74 %

Procedure:
Then, ethyl 3-(4-oxopiperidino)propionate (1.29 g, 6.47 mmol) sad benzylamine (0.85 ml, 7.78 mmol) were dissolved in ethanol (40 ml). A solution of sodium cyanoborohydride (256 mg, 4.22 mmol) dissolved in ethanol (20 ml) was added at room temperature sad acetic acid (1 ml) was further added to adjust its pH to 6-7. The mixture was stirred at room temperature for 18 hours sad added with concentrated hydrochloric acid (3 ml) to adjust the pH to 1-2. The resulting precipitate was collected by filtration and a saturated aqueous sodium hydrogencarbonate solution (150 ml) was added to adjust the mixture to pH 8-9. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtration, low boiling matters were distilled away from the filtrate under reduced pressure to give 1.39 g of ethyl 3-(4-benzylaminopiperidino)propionate as a colorless oil (74%). This oil (1.11 g, 3.82 mmol) was dissolved in ethanol (120 ml) and 10% palladium-carbon (320 mg) was added. The mixture was refluxed under heating for 5 hours under a hydrogen atmosphere. The reaction mixture was filtrated and low boiling matters were distilled away from the filtrate under reduced pressure to give 617 mg of ethyl 3-(4-aminopiperidino)propionate as a colorless oil (81%).
Reaction SMILES: C[C:2](C)([O-:4])C.[Na+].C[O:8][C:9]1[CH:10]=CC=[C:13]2[C:18]=1[CH2:17]C(=O)CC2.CI.[C:22]1([CH3:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[CH3:2][O:4][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:27]=1[C:18]([CH3:13])([CH3:17])[C:9](=[O:8])[CH2:10][CH2:28]2
Reactant: CC(C)(C)[O-]
Reactant: COc1cccc2c1CC(=O)CC2
Reactant: Cc1ccccc1
Agent: [Na+]
Solvent: CI
Product: COc1cccc2c1C(C)(C)C(=O)CC2
Temperature: 15 °C
Reaction time: 0.25 h

Procedure:
To the toluene suspension of sodium t-butoxide (700 mg, 2.5 eq.), 8-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound W1, 500 mg, 2.9 mmol) was added dropwise at 0° C. After 15 minutes, the solution turned into blackish green color. The mixture solution was added dropwise with methyl iodide (1.03 g, 2.5 eq.) and stirred at 15° C. overnight. Brown solid precipitated. The reaction solution was added to saturated aqueous solution of ammonium chloride/diethyl ether under stirring and cooling. After that, the solution was extracted with diethyl ether, and dried over sodium sulfate. After removing the solvent under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 8-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (350 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2.Cl[C:21]1[N:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]2[CH:37]=[C:36]([CH3:38])[C:31]3[NH:32][C:33](=[O:35])[O:34][C:30]=3[CH:29]=2)[CH:22]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN1C(=O)CCC1.O.CN(C=O)C>[CH3:38][C:36]1[C:31]2[NH:32][C:33](=[O:35])[O:34][C:30]=2[CH:29]=[C:28]([NH:27][C:23]2[CH:22]=[C:21]([NH:1][C:2]3[CH:3]=[C:4]4[C:17](=[CH:18][CH:19]=3)[CH2:16][C:6]3([C:14]5[C:9](=[N:10][CH:11]=[CH:12][CH:13]=5)[NH:8][C:7]3=[O:15])[CH2:5]4)[N:26]=[CH:25][N:24]=2)[CH:37]=1
Reactant: Nc1ccc2c(c1)CC1(C2)C(=O)Nc2ncccc21
Reactant: Cc1cc(Nc2cc(Cl)ncn2)cc2oc(=O)[nH]c12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CN1CCCC1=O
Product: Cc1cc(Nc2cc(Nc3ccc4c(c3)CC3(C4)C(=O)Nc4ncccc43)ncn2)cc2oc(=O)[nH]c12
Temperature: 130 °C
Reaction time: 2 h

Procedure:
57 mg (0.23 mmol) 5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, 80 mg (0.23 mmol) 6-(6-chloro-pyrimidin-4-ylamino)-4-methyl-3H-benzoxazol-2-one and 69 mg (0.50 mmol) potassium carbonate were combined in 1.5 mL NMP and stirred for 2 h at 130° C. Then the reaction mixture was cooled, acidified with 1M aqueous hydrochloric acid solution and stirred for 1 h at 50° C. The reaction mixture was diluted with water, the precipitate was taken up in DMF and purified by preparative HPLC. The product-containing fractions were combined and freeze-dried.
Reaction SMILES: [CH:1]1[C:11]2[CH2:10][CH:9]([CH2:12][NH2:13])[C:8]3[CH:14]=[CH:15][CH:16]=[CH:17][C:7]=3[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:18]1(=[O:24])[O:23][CH2:22][CH2:21][CH2:20][CH2:19]1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>O>[CH:1]1[C:11]2[CH2:10][CH:9]([CH2:12][NH:13][C:22](=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][OH:24])[C:8]3[CH:14]=[CH:15][CH:16]=[CH:17][C:7]=3[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=C1CCCCO1
Reactant: NCC1Cc2ccccc2Cc2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: O=C(CCCCO)NCC1Cc2ccccc2Cc2ccccc21
Temperature: 60 °C
Reaction time: 8 h

Procedure:
10,11-Dihydro-5H-dibenzo[a,d]cycloheptene-10-methylamine, γmaxCHCl3 3390, 3300 cm-1, (52.3 g, 0.234 mole), is combined with δ-valerolactone (35 g, 0.35 mole). The mixture is heated for 2 hr. at 150° C (oil bath temperature). After partial cooling, ethanol (250 ml) is added followed by a solution of potassium carbonate (50 g, 0.36 mole) in water (150 ml). The two-phase mixture is stirred at 60° C overnight. The ethanol is removed under reduced pressure and the residual mixture extracted with chloroform. The chloroform solution is washed with water, dried and taken to dryness. The residue is crystallized from benzene (750 ml) -ether (ca 800 ml) affording N-[(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl)methyl]-5-hydroxyvaleramide, m.p. 96° - 98° C, γ maxCHCl3 3630, 3445, 3350, 1663 cm-1.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4]I.[S:6]1[CH:10]=[CH:9][C:8]([C:11]2[CH:19]=[C:18]3[C:14]([CH:15]=[N:16][NH:17]3)=[CH:13][CH:12]=2)=[CH:7]1.[H-].[Na+]>CN(C=O)C>[Cl:1][CH2:2][CH2:3][CH2:4][N:17]1[C:18]2[C:14](=[CH:13][CH:12]=[C:11]([C:8]3[CH:9]=[CH:10][S:6][CH:7]=3)[CH:19]=2)[CH:15]=[N:16]1.[Cl:1][CH2:2][CH2:3][CH2:4][N:16]1[CH:15]=[C:14]2[C:18]([CH:19]=[C:11]([C:8]3[CH:9]=[CH:10][S:6][CH:7]=3)[CH:12]=[CH:13]2)=[N:17]1
Reactant: c1cc(-c2ccc3cn[nH]c3c2)cs1
Reactant: ClCCCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: ClCCCn1cc2ccc(-c3ccsc3)cc2n1
Product: ClCCCn1ncc2ccc(-c3ccsc3)cc21
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 63 %
Yield: 28 %

Procedure:
1-chloro-3-iodopropane (0.14 mL, 1.3 mmol) was added to a DMF (3 mL) solution of 6-(3-thienyl)-1H-indazole (88.4 mg, 0.44 mmol) and sodium hydride (60%, 72 mg, 1.8 mmol) that had been allowed to stir for 5 min at room temperature under argon. The reaction mixture was allowed to stir at room temperature overnight before quenching with brine (20 mL) and partitioning into ethyl acetate (100 mL), and drying over anhydrous sodium sulfate. The solvent was removed in vacuo and flash chromatography (silica gel, 10-20% ethyl acetate in hexane) yielded 1-(3-chloropropyl)-6-(3-thienyl)-1H-indazole (76.6 mg, 63%) as well as the side product 2-(3-chloropropyl)-6-(3-thienyl)-2H-indazole (33.9 mg, 28%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:10](=[O:17])[C@@H:9]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[O:8][C@H:7]([C:24]3[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][C:25]=3[O:31][CH3:32])[C:6]=2[CH:33]=1.[CH2:34](I)[CH3:35].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]([CH3:15])([CH3:14])[CH3:16])[C:10](=[O:17])[C@@H:9]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[O:8][C@H:7]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH2:34][CH3:35])=[CH:26][C:25]=3[O:31][CH3:32])[C:6]=2[CH:33]=1
Reactant: CCOC(=O)C[C@H]1O[C@H](c2ccc(O)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C[C@H]1O[C@H](c2ccc(OCC)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
Reaction time: 3 h

Procedure:
A mixture of ethyl trans-7-chloro-5-(4-hydroxy-2-methoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetate (0.25 g), ethyl iodide (0.06 ml), potassium carbonate (0.15 g) and N,N-dimethylformamide (200 ml) was stirred for 3 h. The mixture was diluted with water (50 ml) and extracted with ethyl acetate (100 ml). The extract was washed with 1N hydrochloric acid and aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated in vacuo to give ethyl trans-7-chloro-5-(4-ethoxy-2-methoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetate (0.24 g) as colorless crystals (mp=164°-166° C.).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([Cl:17])[CH:10]=2)[N:5]=[C:4]([NH:18][CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[N:3]=1.[CH3:26][N:27]1[CH2:32][CH2:31][CH:30]([NH:33][CH3:34])[CH2:29][CH2:28]1.[OH-].[Na+].Cl>O1CCOCC1.CC(C)=O>[OH-:15].[NH4+:3].[Cl:17][C:11]1[CH:10]=[C:9]([NH:8][C:6]2[N:5]=[C:4]([NH:18][CH2:19][CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[N:3]=[C:2]([N:33]([CH3:34])[CH:30]3[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]3)[N:7]=2)[CH:14]=[CH:13][C:12]=1[O:15][CH3:16]
Reactant: COc1ccc(Nc2nc(Cl)nc(NCC3CCCCC3)n2)cc1Cl
Reactant: CNC1CCN(C)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CC(C)=O
Product: COc1ccc(Nc2nc(NCC3CCCCC3)nc(N(C)C3CCN(C)CC3)n2)cc1Cl
Product: [NH4+]
Temperature: 80 °C
Reaction time: 2 h
Yield: 17.3 %

Procedure:
To a sample of 102 (0.286 g, 1.0 mmol) dissolved in 1,4-dioxane (4 mL) was added a solution of N-methyl-4(methylamino)piperidine (0.15 mL, 1.0 mmol) in acetone (1 mL) followed by addition of a NaOH solution (0.0462 g, 1.0 mmol dissolved in 1 mL of H2O). The reaction mixture was allowed to stir at about 80° C. for about 2 hours. The reaction mixture was poured over crushed ice and neutralized with 10% HCl (aq). The resulting solid was collected by vacuum filtration, washed with water and dried under vacuum overnight. Column chromatography (silica gel, 96:3:1 dichloromethane:methanol:conc. ammonium hydroxide) yielded a light purple solid 103 (41 mg, 9%), mp 84° C.; HPLC: YMC Pack Pro C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 12.7 min, 97% purity); 1H NMR (600 MHz, CDCl3, 55° C.) δ 7.98 (s, 1H), 7.18 (S, 1H), 6.85 (d, J=9 Hz, 1H), 6.58 (s, 1H), 4.89 (s, 1H), 4.58–4.62 (m, 1H), 3.87 (s, 3H), 3.25 (t, J=6.6 Hz, 2H), 3.05 (s, 3H), 2.94 (d, J=11.4 Hz, 2H), 2.31 (s, 3H), 2.15 (S, 2H), 1.86 (dq, J=12, 4.2 Hz, 3H), 1.57–1.78 (m, 8H), 1.15–1.30 (m, 4H), 1.00 (dq, J=11.4, 3 Hz, 2H); MS (ESI): m/z 476 (37.7), 474 (M+H, 100), 410 (1.4).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.Cl[C:26](Cl)([O:28][C:29](=[O:35])OC(Cl)(Cl)Cl)Cl.[CH:37]1(CO)[CH2:39][CH2:38]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH:20][C:29](=[O:35])[O:28][CH2:26][CH:37]2[CH2:39][CH2:38]2)=[C:18]([CH3:24])[CH:17]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: OCC1CC1
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2nccc(Oc3cc(C)c(NC(=O)OCC4CC4)cc3C)c2cc1OC
Yield: 78.3 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopropylmethanol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 74%).
Reaction SMILES: Cl.CC([N:6]([CH2:10][CH:11]([NH:19][C:20]([C:22]1[N:23]([CH3:33])[CH:24]=[C:25]([C:27]2[N:31]([CH3:32])[N:30]=[CH:29][CH:28]=2)[CH:26]=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)C(=O)[O-])(C)C>O1CCOCC1.C(Cl)(Cl)Cl.CO>[NH2:6][CH2:10][CH:11]([NH:19][C:20]([C:22]1[N:23]([CH3:33])[CH:24]=[C:25]([C:27]2[N:31]([CH3:32])[N:30]=[CH:29][CH:28]=2)[CH:26]=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Cn1cc(-c2ccnn2C)cc1C(=O)NC(Cc1ccccc1)CN(C(=O)[O-])C(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: Cn1cc(-c2ccnn2C)cc1C(=O)NC(CN)Cc1ccccc1
Yield: 32.3 %

Procedure:
HCl in Dioxane (4M, 2 mL) was added to a solution of 1,1-dimethylethyl[2-({[1-methyl-4-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrol-2-yl]carbonyl}amino)-3-phenylpropyl]carbamate (285 mg, 0.65 mmol) in CHCl3/MeOH (10:1, 10 mL) affording the title compound as a white solid (71 mg, 0.21 mmol, 32%): LC-MS (ES) m/z 338 (M+H)+, 1H NMR (400 MHz, MeOD) δ ppm 2.77-2.93 (m, 4H) 3.86 (s, 3H) 3.92 (s, 3H) 4.29 (ddd, J=8.15, 4.74, 2.02 Hz, 1H) 6.30 (d, J=2.02 Hz, 1H) 6.94 (d, J=1.77 Hz, 1H) 7.14 (d, J=1.77 Hz, 1H) 7.19 (td, J=5.56, 3.03 Hz, 1H) 7.25-7.30 (m, 4H) 7.41 (d, J=1.77 Hz, 1H).
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][C:7]1[C:8](=[O:15])[C@@H]2[O:14][CH2:13][C@H:11]([CH:12]=1)O2.[C:16](=[O:19])([O-])[OH:17].[Na+].[CH3:21]O>>[CH3:21][C@@:16]1([O:19][C@H:11]([CH2:13][OH:14])[CH:12]=[C:7]([CH3:6])[C:8]1=[O:15])[OH:17]
Reactant: O=C([O-])O
Reactant: CC1=C[C@H]2CO[C@H](O2)C1=O
Reactant: CO
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: CC1=C[C@@H](CO)O[C@](C)(O)C1=O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
0.1 ml of concentrated sulfuric acid was added to 30 ml of a dry methanol solution containing 500 mg of 1,6-anhydro-3,4-dideoxy-3-methyl-β-D-glycero-hex-3-enopyranos-2-ulose (Intermediate No. 2), and the mixture was stirred at room temperature for 48 hours. Then, 30 ml of a saturated sodium hydrogencarbonate aqueous solution was added thereto, and the mixture was stirred at room temperature for 15 minutes and then concentrated under reduced pressure. Then, 200 ml of ethyl acetate was added thereto, and the mixture was washed three times with 200 ml of a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained syrup crude product was purified by silica gel column chromatography (ethyl acetate: hexane=2:3) to obtain 350 mg of the desired compound (Intermediate No. 20) as a colorless liquid. The NMR analytical data of this product are as follows. 1H NMR(CDCl3,400 MHz): 1.86(3H,m); 1.95(1H,t,J=6.0Hz); 3.54(3H,s); 3.76(1H,ddd,J=11.2,6.8,6.0Hz); 3.84(1H,ddd,J=11.2,6.0,3.6Hz); 4.63(1H,m); 4.80(1H,s); 6.68(1H,m)
Reaction SMILES: [C:1](ON=O)([CH3:4])([CH3:3])[CH3:2].[CH2:8]([Br:11])[CH:9]=C.[N+:12]([C:15]1C=C(C=[C:20]([N+:22]([O-:24])=[O:23])[CH:21]=1)N)([O-:14])=[O:13].NC1C=CC=CC=1>CC#N>[N+:12]([C:15]1[CH:4]=[C:1]([CH2:2][C:8]([Br:11])=[CH2:9])[CH:3]=[C:20]([N+:22]([O-:24])=[O:23])[CH:21]=1)([O-:14])=[O:13]
Reactant: CC(C)(C)ON=O
Reactant: Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Reactant: C=CCBr
Solvent: Nc1ccccc1
Solvent: CC#N
Product: C=C(Br)Cc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Temperature: 13 °C
Reaction time: 1 h
Yield: 92.9 %

Procedure:
To a solution of t-butylnitrite (535 μl, 4.5 mmol) and allyl bromide (3.9 ml, 45.0 mmol) in CH3CN (3 ml), 3,5-dinitroaniline (549 mg, 3.0 mmol) was added during 20 minutes, while maintaining the temperature of the reaction mixture at 11-15° C. At the end of the addition of the aniline extra t-butylnitrite (180 μl, 1.5 mmol) was added to the reaction mixture which then was stirred at 22° C. for one hour. The volatile material in the reaction mixture was removed at reduced pressure. Column chromatography (heptane-ethyl acetate 10:1) gave 800 mg (93%) 3,5-dinitro-1-(2-bromo-2-propenyl)benzene as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.98, (t, 1H, J=2.1 Hz), 8.47, (d, 2H, J=2.1 Hz), 5.89, (m, 1H), 5.71, (d, 1H, J=2.1 Hz), 4.00, (s, 2H); 13C NMR (CDCl3, 100 MHz) δ 149.05, 142.1, 129.6, 129.3, 121.4, 118.2, 47.3.
Reaction SMILES: [NH2:1][C@H:2]([CH3:5])[CH2:3][OH:4].[CH:6](=O)[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[NH3:1].[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][NH:1][C@H:2]([CH3:5])[CH2:3][OH:4])=[CH:8][CH:9]=1
Reactant: COc1ccc(C=O)cc1
Reactant: C[C@@H](N)CO
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc(CN[C@H](C)CO)cc1
Product: N
Temperature: 25 °C
Reaction time: 48 h

Procedure:
(R)-(−)-2-Amino-1-propanol (10.36 ml, 133 mmol) was added dropwise to a solution of p-anisaldehyde (5.85 g, 42.9 mmol) in methanol (90 ml), and the solution was cooled in an ice-bath. Acetic acid (2.5 ml) and sodium triacetoxyborohydride (10.0 g, 47.2 mmol) were added and the reaction mixture was allowed to warm to room temperature over an hour. The solution was warmed to 40° C. and stirred for a further 48 hours then concentrated under reduced pressure. The residue was partitioned between saturated sodium bicarbonate solution (50 ml) and dichloromethane (100 ml) and the layers were separated. The aqueous phase was extracted with further dichloromethane (10×50 ml), and the combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The residue was purified twice by column chromatography on silica gel using an elution gradient of dichloromethane:methanol:0.88 ammonia (97:3:0.3 to 90:10:1) to afford the title compound, 6.0 g. 1H-NMR (CDCl3, 400 MHz) δ: 1.04 (d, 3H), 2.80 (m, 1H), 322 (dd, 1H), 3.58 (dd, 1H), 3.62 (d, 1H), 3.78 (m, 4H), 6.82 (d, 2H), 7.20 (d, 2H). LRMS: m/z (ES+) 196 [MH+]. [α]D=−34.85 (c=0.137, methanol)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:16]=2[CH2:17][N:18]2[CH:23]=[CH:22][C:21]([NH:24][CH2:25]C)=[N:20][C:19]2=[O:27])=[CH:4][CH:3]=1.Cl[C:29]1C=CN(CC2N3C=CC=CC3=NC=2C2C=CC(Cl)=CC=2)C(=O)N=1.CNC>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:16]=2[CH2:17][N:18]2[CH:23]=[CH:22][C:21]([N:24]([CH3:29])[CH3:25])=[N:20][C:19]2=[O:27])=[CH:4][CH:3]=1
Reactant: CCNc1ccn(Cc2c(-c3ccc(Cl)cc3)nc3ccccn23)c(=O)n1
Reactant: O=c1nc(Cl)ccn1Cc1c(-c2ccc(Cl)cc2)nc2ccccn12
Agent: CNC
Product: CN(C)c1ccn(Cc2c(-c3ccc(Cl)cc3)nc3ccccn23)c(=O)n1

Procedure:
The title compound was prepared according to the experimental for compound 132 from 4-chloro-1-((2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)pyrimidin-2(1H)-one and dimethylamine. M/e+ 380 for C20H19ClN5O (M+H)+; 1H-NMR (400 MHz, CDCl3) δ 8.44 (d, J=6.9 Hz, 1H), 7.67 (d, J=8.4 Hz, 2H), 7.63 (d, J=8.8 Hz, 1H), 7.47 (d, J=8.4 Hz, 2H), 7.28 (d, J=6.9 Hz, 1H), 6.86 (t, J=6.6 Hz, 1H), 6.75 (d, J=7.7 Hz, 1H), 5.63 (d, J=7.7 Hz, 1H), 5.56 (s, 2H), 3.18 (s, 3H), 2.96 (s, 3H) ppm.