Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7](=[N:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:6][CH:5]1[CH3:22])(=[O:3])[CH3:2].C([BH3-])#N.[Na+].Cl.C(=O)([O-])O.[Na+]>CO>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:6][C@@H:5]1[CH3:22])(=[O:3])[CH3:2]
Reactant: CC(=O)N1c2ccccc2C(=Nc2ccccc2F)CC1C
Agent: Cl
Agent: O=C([O-])O
Agent: [BH3-]C#N
Solvent: CO
Product: CC(=O)N1c2ccccc2[C@H](Nc2ccccc2F)C[C@@H]1C
Temperature: 50 °C
Reaction time: 18 h
Yield: 87.7 %

Procedure:
[Step 2] 60 mg of 1-acetyl-2-methyl-4-[(2-fluorophenyl)imino]-1,2,3,4-tetrahy droquinoline and 28 mg of sodium cyanoborohydride were dissolved in 2 mL of methanol, and the solution was stirred for 18 hours at 50° C. After completion of the reaction, 1 N hydrochloric acid was added to the reaction liquid, and the mixture was stirred for 30 minutes. The reaction liquid was neutralized with a saturated aqueous solution of sodium hydrogen carbonate, and then was extracted with chloroform. The organic layer was washed with a saturated solution of sodium hydrogen carbonate and saturated brine, dehydrated over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by using silica gel chromatography (diethyl ether:hexane=2:1), and thus 53 mg (88%) of the title compound was obtained as a colorless oily substance.
Reaction SMILES: [CH:1]1([CH2:4][NH:5][C:6](=[O:17])[NH:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH2:3][CH2:2]1.[F:18][C:19]([F:42])([F:41])[C:20]([C:26]1[CH:31]=[CH:30][C:29]([CH2:32][N:33]2[CH2:38][CH2:37][NH:36][CH2:35][C@@H:34]2[CH2:39][OH:40])=[CH:28][CH:27]=1)([OH:25])[C:21]([F:24])([F:23])[F:22].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[CH:1]1([CH2:4][NH:5][C:6]([NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:12]([N:36]3[CH2:37][CH2:38][N:33]([CH2:32][C:29]4[CH:30]=[CH:31][C:26]([C:20]([OH:25])([C:19]([F:18])([F:41])[F:42])[C:21]([F:24])([F:22])[F:23])=[CH:27][CH:28]=4)[C@@H:34]([CH2:39][OH:40])[CH2:35]3)=[O:14])=[CH:15][CH:16]=2)=[O:17])[CH2:2][CH2:3]1
Reactant: O=C(NCC1CC1)Nc1ccc(C(=O)O)cc1
Reactant: OC[C@H]1CNCCN1Cc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NCC1CC1)Nc1ccc(C(=O)N2CCN(Cc3ccc(C(O)(C(F)(F)F)C(F)(F)F)cc3)[C@@H](CO)C2)cc1
Reaction time: 3 h
Yield: 35.3 %

Procedure:
To a solution of 4-(3-(cyclopropylmethyl)ureido)benzoic acid (0.487 mmol, 114 mg), (R)-1,1,1,3,3,3-hexafluoro-2-(4-((2-(hydroxymethyl)piperazin-1-yl)methyl)phenyl)propan-2-ol (0.443 mmol, 165 mg) and triethylamine (1.330 mmol, 0.185 mL, 135 mg) in dichloromethane (4 mL) was added 1-propanephosphonic acid cyclic anhydride (0.665 mmol, 0.395 mL, 423 mg, 50% solution in ethyl acetate). The reaction was stirred for 3 hours and then was diluted with dichloromethane/saturated sodium hydrogen carbonate (aqueous). The organic layer was separated, dried (magnesium sulfate) and concentrated under reduced pressure. The residue was purified by silica column chromatography (eluting with ethyl acetate to 5% methanol/ethyl acetate and basic reverse phase HPLC to afford the title compound (92 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:9][CH:10]([NH:19][C:20]([NH:22][CH2:23][CH2:24]O)=[S:21])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[C:12]=2[CH3:18])[CH:5]=[C:6]([CH3:8])[CH:7]=1>Cl>[S:21]1[CH2:24][CH2:23][N:22]=[C:20]1[NH:19][CH:10]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[C:12]=1[CH3:18])[CH2:9][C:4]1[CH:3]=[C:2]([CH3:1])[CH:7]=[C:6]([CH3:8])[CH:5]=1
Reactant: Cc1cc(C)cc(CC(NC(=S)NCCO)c2cccc(C)c2C)c1
Agent: Cl
Product: Cc1cc(C)cc(CC(NC2=NCCS2)c2cccc(C)c2C)c1
Yield: 74.6 %

Procedure:
A mixture of the above 1-[2-(3,5-Dimethyl-phenyl)-1-(2,3-dimethyl-phenyl)-ethyl]-3-(2-hydroxy-ethyl)-thiourea (94.7 g) and concentrated hydrochloric acid (700 ml) was heated under reflux for 2 hours. The hydrochloric acid phase was decanted carefully and the remainder dissolved in ethyl acetate and thoroughly washed three times with potassium carbonate solution (5 wt % in water), three times with water and dried over sodium sulphate. The solvent was removed by evaporation and the remainder titurated with a solution of light petrol ether/ethyl acetate (20/1), filtrated to yield the product (4,5-dihydro-thiazol-2-yl)-[2-(3,5-dimethyl-phenyl)-1-(2,3-dimethyl-phenyl)-ethyl]-amine [specific compound example C.33 of table C] as an off-white solid (67.1 g)
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][O:14][C@H:13]([C@@H:17]([OH:21])[C:18]([OH:20])=O)[C:12]2=[O:22])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=1[Cl:32].NC1C=C2C(=CC=1)C(N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=NC=C2>>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH2:16][CH2:15][O:14][C@H:13]([C@@H:17]([OH:21])[C:18]([NH:23][C:24]3[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=3[Cl:32])=[O:20])[C:12]2=[O:22])=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccc(N2CCO[C@H]([C@@H](O)C(=O)O)C2=O)cc1
Reactant: N#Cc1ccc(N)c(Cl)c1
Agent: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1nccc2cc(N)ccc12
Product: CC(C)(C)c1ccc(N2CCO[C@H]([C@@H](O)C(=O)Nc3ccc(C#N)cc3Cl)C2=O)cc1

Procedure:
According to the Step 1-3 in synthetic method for EXAMPLE 1, a cyclic carbonate analogue (0.2 g) derived from compound 52-4 and 4-amino-3-chlorobenzonitrile (91.6 mg) were used instead of 1-2 and 6-amino-1-bis(tert-butoxy carbonyl)aminoisoquinoline, under high concentration condition (1M), to obtain compound 66-1 (93.1 mg) as a colorless amorphous solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH3:30])=[C:6]([C:8]([CH3:28])([CH3:27])[CH2:9][C:10]([NH2:26])([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:11]([F:14])([F:13])[F:12])[CH:7]=1.[C:31](OC(=O)C)(=[O:33])[CH3:32]>ClC(Cl)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH3:30])=[C:6]([C:8]([CH3:27])([CH3:28])[CH2:9][C:10]([NH:26][C:31](=[O:33])[CH3:32])([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:11]([F:12])([F:14])[F:13])[CH:7]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc(F)cc1C(C)(C)CC(N)(Cc1ccnc2ccccc12)C(F)(F)F
Solvent: CC(Cl)Cl
Product: COc1ccc(F)cc1C(C)(C)CC(Cc1ccnc2ccccc12)(NC(C)=O)C(F)(F)F
Temperature: 85 °C
Reaction time: 16 h
Yield: 73.5 %

Procedure:
A solution of 3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butylamine (42.0 mg, 0.1 mmol) in dichloroethane (4 mL) was treated with acetic anhydride (71 μL, 1.0 mmol). The mixture was stirred for 16 h at 85° C. and quenched with NaHCO3 (sat, 4 mL). Phases were separated and the aqueous layer was extracted with CHCl3 (3×2 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified on SiO2 (50%–70%, EtOAc:hexanes) to give 34.0 mg (74%) of the title product.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]#[N:12])[CH:2]=1.C[Si]([N-:17][Si](C)(C)C)(C)C.[Li+]>C(OCC)C>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([NH2:17])=[NH:12])[CH:2]=1
Reactant: N#Cc1cnc2ccccc2c1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOCC
Product: N=C(N)c1cnc2ccccc2c1
Reaction time: 3 h

Procedure:
Quinoline-3-nitrile (1.0 g) was dissolved in diethyl ether (30 mL) and treated with lithium bis(trimethylsilyl)amide (1.0 M in THF, 13 mL). The reaction was stirred for 3 hours, then washed 3 times with 1 N HCl (50 mL). The combined aqueous washes were neutralized with 6 N NaOH and extracted 6 times with ethyl acetate (50 mL). The ethyl acetate extractions were dried over sodium sulfate and the solvent was evaporated to provide 0.63 g of quinoline-3-carboxamidine.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C:11]2[N:12]=[CH:13][N:14]([C:16]3[CH:21]=[CH:20][C:19](I)=[CH:18][CH:17]=3)[CH:15]=2)=[O:8])=[CH:4][CH:3]=1.[C:23]([NH:26][C:27]1[CH:32]=[CH:31][NH:30][C:29](=[O:33])[N:28]=1)(=[O:25])[CH3:24].OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I>[C:23]([NH:26][C:27]1[CH:32]=[CH:31][N:30]([C:19]2[CH:20]=[CH:21][C:16]([N:14]3[CH:15]=[C:11]([CH2:10][NH:9][C:7]([C:5]4[S:6][C:2]([Cl:1])=[CH:3][CH:4]=4)=[O:8])[N:12]=[CH:13]3)=[CH:17][CH:18]=2)[C:29](=[O:33])[N:28]=1)(=[O:25])[CH3:24]
Reactant: CC(=O)Nc1cc[nH]c(=O)n1
Reactant: O=C(NCc1cn(-c2ccc(I)cc2)cn1)c1ccc(Cl)s1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: Oc1cccc2cccnc12
Solvent: CS(C)=O
Product: CC(=O)Nc1ccn(-c2ccc(-n3cnc(CNC(=O)c4ccc(Cl)s4)c3)cc2)c(=O)n1
Temperature: 130 °C
Yield: 3.6 %

Procedure:
A mixture of 5-chloro-N-((1-(4-iodophenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide 1-6 (80 mg, 0.18 mmol), N4-acetylcytosine (65 mg, 0.42 mmol), 8-hydroxyquinoline (12 mg, 0.083 mmol) and K2CO3 (60 mg, 0.43 mmol) in DMSO (2 mL) was degassed with Ar before being charged with CuI (15 mg, 0.079 mmol). The mixture in a sealed tube was heated at 130° C. overnight. The mixture was then purified by HPLC to give the titled compound (3 mg). MS 469.3 and 471.2 (M+H, Cl pattern).
Reaction SMILES: [O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5][C:4]([C:12]2[N:17]=[C:16]([NH:18][CH2:19][C:20]([O:22]C(C)(C)C)=[O:21])[N:15]=[CH:14][CH:13]=2)=[N:3]1.C(OC(C)C)(C)C>FC(F)(F)C(O)=O>[O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5][C:4]([C:12]2[N:17]=[C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])[N:15]=[CH:14][CH:13]=2)=[N:3]1
Reactant: CC(C)(C)OC(=O)CNc1nccc(-c2nc(=O)c3ccccc3s2)n1
Solvent: CC(C)OC(C)C
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)CNc1nccc(-c2nc(=O)c3ccccc3s2)n1
Reaction time: 0.5 h
Yield: 76.6 %

Procedure:
tert-Butyl {[6-(4-oxo-4H-1,3-benzothiazin-2-yl)-2-pyrimidinyl]amino}acetate (0.20 g, 0.54 mmol) was dissolved in trifluoroacetic acid (5 ml), and the mixture was stirred for 0.5 hr. Diisopropyl ether was added thereto. The obtained precipitates were recrystallized from ethanol to give the titled compound (0.13 g, 75%) as pale yellow crystals
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[CH3:7][C:8]([CH:10]1[CH2:15][CH2:14][C:13]([CH2:16][NH2:17])=[CH:12][CH2:11]1)=[CH2:9].C(N(CC)CC)C.[Cl-].[Na+]>>[CH3:9][C:8]([CH:10]1[CH2:15][CH2:14][C:13]([CH2:16][NH:17][C:2](=[O:3])[O:4][CH2:5][CH3:6])=[CH:12][CH2:11]1)=[CH2:7]
Reactant: CCOC(=O)Cl
Reactant: C=C(C)C1CC=C(CN)CC1
Agent: [Cl-]
Agent: [Na+]
Solvent: CCN(CC)CC
Product: C=C(C)C1CC=C(CNC(=O)OCC)CC1

Procedure:
Ethyl chloroformate 1.1 eq, [4-(1-methylethenyl)-1-cyclohexen-1-yl]methylamine 1.0 eq, triethylamine 1.3 eq, quench with 10% sodium chloride solution, yield=37%.
Reaction SMILES: [C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][CH:8]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:9]([OH:11])=[O:10])=[CH:3][CH:2]=1.IC.[H-].[Na+].[C:30](OCC)(=O)C>O1CCCC1.O>[C:1]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH3:30])[C:9]([OH:11])=[O:10])=[CH:5][CH:6]=1
Reactant: CCOC(C)=O
Reactant: CC(C)(C)OC(=O)NC(Cc1ccc(-c2ccccc2)cc1)C(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CI
Product: CN(C(=O)OC(C)(C)C)[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)O
Temperature: 0 °C
Reaction time: 120 h

Procedure:
3-(1,1′-Biphenyl-4-yl)-2-tert-butoxycarbonylaminopropionic acid (5.0 g; 14.66 mmol) was dissolved in dry tetrahydrofuran (45 mL). Iodomethane (7.3 mL; 117.3 mmol) was added and the reaction mixture was cooled to 0° C. Sodium hydride (1.75 g; as 44.0 mmol) was added and the reaction mixture was stirred for 5 days at room temperature. Ethyl acetate (50 mL) was added and water (20 mL) was added dropwise. The solvent was removed in vacuo and the residue was dissolved in an aqueous solution of sodium hydrogen carbonate (saturated; 50 mL) and washed with diethyl ether (30 mL). The aqueous phase was acidified to pH 3 using citric acid (5%) and extracted with ethyl acetate (3×50 mL). The organic phase was washed with an aqueous solution of sodium thiosulfate (5%; 75 mL) and dried (magnesium sulfate). The solvent was removed in vacuo to afford 3.85 g of (2R)-3-(1,1′-biphenyl-4-yl)-2-(N-tert-butoxycarbonyl-N-methylamino)propionic acid.
Reaction SMILES: [O:1]=[C:2]1[C:8]2=[CH:9][C:10]3[CH:11]=[CH:12][C:13]([C:16]([NH:18][C:19]4[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=4[C:21]([O:23]C)=[O:22])=[O:17])=[CH:14][C:15]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1.[OH-].[Na+].Cl.O>CO>[O:1]=[C:2]1[C:8]2=[CH:9][C:10]3[CH:11]=[CH:12][C:13]([C:16]([NH:18][C:19]4[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=4[C:21]([OH:23])=[O:22])=[O:17])=[CH:14][C:15]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1
Reactant: COC(=O)c1ccccc1NC(=O)c1ccc2cc3n(c2c1)CCCNC3=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(Nc1ccccc1C(=O)O)c1ccc2cc3n(c2c1)CCCNC3=O
Temperature: 60 °C
Yield: 92.7 %

Procedure:
A suspension of methyl 2-{[(1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indol-8-yl)carbonyl]amino}benzoate (503 mg, 1.3 mmol) in methanol (7 mL) and 2M NaOH solution (2.0 mL, 4.0 mmol) is heated at 60° C. for 3 h. 1M HCl solution (10 mL) and water (80 mL) are added. The resulting solid is collected by filtration and dried to afford the title compound (438 mg, 90%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[C:12]1[N:20]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[CH:13]=1.[H-].[Na+].Cl[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>CN(C)C=O>[CH2:38]([O:37][C:35](=[O:36])[CH2:34][N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[C:6]([C:12]2[N:20]([S:21]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[CH:13]=2)=[CH:7]1)[CH3:39]
Reactant: CCOC(=O)CCl
Reactant: COc1ccc2[nH]cc(-c3cc4cccnc4n3S(=O)(=O)c3ccc(C)cc3)c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1cc(-c2cc3cccnc3n2S(=O)(=O)c2ccc(C)cc2)c2cc(OC)ccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.5 %

Procedure:
A solution of 2-(5-methoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [6.6 g, Reference Example 12(a)] in dimethylformamide (100 mL), under a nitrogen atmosphere, was treated with sodium hydride (700 mg, 60% dispersion in oil). After stirring at ambient temperature for 30 minutes the mixture was treated dropwise with ethyl chloroacetate (2.0 mL, 23.75 mmol) and stirring was continued for an additional 4 hours. The reaction mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, then dried over sodium sulfate and then evaporated to give the title compound (5.77 g) as a yellow solid, MS: 504(MH+). HPLC (METHOD A): RT=11.88 minutes.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Cl.[OH:8][C:9]([CH3:29])([CH3:28])[CH2:10][NH:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=[CH:14][C:13]=1[NH:22][C:23](=O)[CH2:24][O:25][CH3:26]>O.C(O)C.[Cl-].[Na+].O>[CH3:26][O:25][CH2:24][C:23]1[N:11]([CH2:10][C:9]([CH3:29])([OH:8])[CH3:28])[C:12]2[C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:15]=[CH:14][C:13]=2[N:22]=1
Reactant: COCC(=O)Nc1cnc2ccccc2c1NCC(C)(C)O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: O
Solvent: CCO
Product: COCc1nc2cnc3ccccc3c2n1CC(C)(C)O
Temperature: 25 °C
Yield: 90.9 %

Procedure:
A solution of potassium carbonate (3.4 g, 24.3 mmol) in water (9 mL) was added to a stirred suspension of N-{4-[(2-hydroxy-2-methylpropyl)amino]quinolin-3-yl}-2-methoxyacetamide hydrochloride (5.5 g, 16.2 mmol) in ethanol (23 mL). The reaction mixture was heated at reflux for 1.5 hours, then was allowed to cool to room temperature. The mixture was concentrated under reduced pressure to yield an aqueous slurry that was diluted with water (50 mL) and a small amount of brine. The mixture was extracted with dichloromethane (2×50 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude oil was purified by flash chromatography (silica gel, 5% methanol in dichloromethane) to yield 4.2 g of 1-[2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as an oil that slowly solidified.
Reaction SMILES: [Cl-:1].[Cl-].[CH3:3][Zr:4]([CH3:26])(=[SiH2:25])([CH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[C:16]1[CH3:24])[CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:14].[H][H]>ClCCl.[Pt]=O>[Cl-:1].[Cl-:1].[CH3:26][Zr:4]([CH3:3])(=[SiH2:25])([CH:15]1[C:23]2[CH2:22][CH2:21][CH2:20][CH2:19][C:18]=2[CH:17]=[C:16]1[CH3:24])[CH:5]1[C:13]2[CH2:12][CH2:11][CH2:10][CH2:9][C:8]=2[CH:7]=[C:6]1[CH3:14]
Reactant: CC1=Cc2ccccc2C1[Zr](C)(C)(=[SiH2])C1C(C)=Cc2ccccc21
Reactant: [H][H]
Agent: O=[Pt]
Agent: [Cl-]
Solvent: ClCCl
Product: CC1=CC2=C(CCCC2)C1[Zr](C)(C)(=[SiH2])C1C(C)=CC2=C1CCCC2

Procedure:
Dimethylsilylenebis(2-methyl-4,5,6,7-tetrahydroindenyl)zirconium dichloride was prepared by first synthesizing dimethylsilylenebis(2-methylindenyl)zirconium dichloride as in Example-A13, and the latter in an amount of 1.0 g was dissolved in 150 ml of dichloromethane and was introduced in an autoclave of 500 ml capacity in which it was reacted in the presence of 0.1 g of platinum oxide added with hydrogen under a pressure of 50 kg/cm2G at room temperature for 5 hours. The platinum oxide catalyst was then removed and the solvent used was removed in vacuo whereby a solid was obtained, which solid was extracted with toluene and recrystallization was conducted to give 0.32 g of dimethylsilylenebis(2-methyl-4,5,6,7-tetrahydroindenyl)zirconium dichloride desired.
Reaction SMILES: [C:1]1(=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH:3]=[CH:2]1.[CH2:13]([N:21]1[CH:25]=[CH:24][CH:23]=[CH:22]1)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[CH2:13]([N:21]1[CH:22]=[CH:23][CH:24]=[C:25]1[C:3]1[C:4](=[O:11])[C:5]2[C:10]([C:1](=[O:12])[CH:2]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCn1cccc1
Reactant: O=C1C=CC(=O)c2ccccc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClC(Cl)Cl
Product: CCCCCCCCn1cccc1C1=CC(=O)c2ccccc2C1=O
Yield: 32 %

Procedure:
6.32 millimol of 1,4-naphthoquinone and 3.16 millimol of N-octylpyrrole were stirred in 50 ml of chloroform in a round-bottomed flask for 5 hours at room temperature, the reaction being catalysed by addition of a few milligrams of para-toluenesulphonic acid. The reaction medium was diluted with 50 ml of chloroform and then washed four times with 50 ml of water and finally with saturated aqueous NaCl solution. The resulting organic phase was dried over Na2SO4 and then concentrated under vacuum. The product 2-(1-octyl-1H-pyrrol-2-yl)-[1,4]-naphthoquinone was thus isolated, in the form of an oil, in a yield of 32% after purification by chromatography on a column of silica.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:13](=[O:15])[CH3:14])[CH2:11][CH2:10][C:9](=O)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]12[CH2:11][CH2:10][C:9]([NH:23][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([CH2:8][CH2:7]1)[CH2:14][C:13]2=[O:15])=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(C(C)=O)CCC(=O)CC1
Reactant: NCc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)C12CCC(NCc3ccccc3)(CC1)CC2=O
Temperature: 25 °C

Procedure:
Toluene (100 mL) was added to 1-acetyl-4-oxocyclohexyl carboxylic acid ethyl ester (8.0 g, 38 mmol) and then the resulting mixture was stirred. To the mixture, there were added benzylamine (5.3 mL, 49 mmol) and p-toluenesulfonic acid monohydrate (76 mg, 0.40 mmol). The mixture was refluxed for 8 hours with a Dean-Stark apparatus under the dehydration conditions. After cooled to room temperature, the mixture was concentrated under reduced pressure to give a crude product. The resulting crude product was treated according to the silica gel column chromatography (eluting solution: hexane/ethyl acetate) to thus obtain a mixture of the desired product and an imine derivative thereof. The mixture was dissolved in chloroform (200 mL) and then the resulting solution was treated with a 0.5 mol/L hydrochloric acid solution (100 mL). The suspended organic phase was separated, then treated with a 5% aqueous solution of sodium hydrogen carbonate and then separated. The organic phase was dried over anhydrous magnesium sulfate, followed by the removal of the drying agent through filtration and the subsequent concentration of the resulting filtrate under reduced pressure to thus give the desired product as a white solid. (2.9 g; yield: 26%).
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[CH:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@:8]3([OH:22])[CH2:9][CH2:10][C:11]2=[O:21])[CH2:3]1.[C:23](OC(=O)C)(=[O:25])[CH3:24].C([O-])(=O)C>N1C=CC=CC=1>[C:23]([O:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[CH:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@:8]3([OH:22])[CH2:9][CH2:10][C:11]2=[O:21])[CH2:3]1)(=[O:25])[CH3:24]
Reactant: C[C@]12CC[C@H](O)CC1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@]12O
Reactant: CC(=O)OC(C)=O
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(CC[C@@H]3[C@@H]2CC[C@]2(C)C(=O)CC[C@]32O)C1

Procedure:
3β,14β-Dihydroxyandrostan-17-one-(70 mg.) was dissolved in 5 ml. of pyridine and treated with 1 ml. of acetic anhydride at room temperature for 15 hours. After evaporation of solvents, the residue was crystallized from ether to give 70 mg. of the acetate, m.p. 182°-184°.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[C:9]([F:29])=[C:10](F)[C:11]3[C:21](=[O:22])[C:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:19][N:13]4[C@@H:14]([CH3:18])[CH2:15][O:16][C:17]=2[C:12]=34)[CH:5]=[C:4]([CH3:30])[N:3]=1.[CH2:31]([SH:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[H-].[Na+]>O1CCCC1.C([O-])(=O)C.[Na+]>[CH2:31]([S:38][C:10]1[C:11]2[C:21](=[O:22])[C:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:19][N:13]3[C@@H:14]([CH3:18])[CH2:15][O:16][C:17]([C:12]=23)=[C:8]([C:6]2[CH:7]=[C:2]([CH3:1])[N:3]=[C:4]([CH3:30])[CH:5]=2)[C:9]=1[F:29])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: SCc1ccccc1
Reactant: CCOC(=O)c1cn2c3c(c(-c4cc(C)nc(C)c4)c(F)c(F)c3c1=O)OC[C@@H]2C
Agent: CC(=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cn2c3c(c(-c4cc(C)nc(C)c4)c(F)c(SCc4ccccc4)c3c1=O)OC[C@@H]2C
Reaction time: 1 h

Procedure:
To a suspension of 2.78 g ethyl (S)-10-(2,6-dimethyl-4-pyridinyl)-8,9-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate in 67 ml tetrahydrofuran cooled in an ice-bath was added 0.79 ml benzyl mercaptan, followed by 0.34 g sodium hydride (60% in oil, washed with hexane before use) portionwise, and the mixture was stirred for one hour. An additional 0.079 ml benzyl mercaptan was added and stirring continued at room temperature for 3 hours. The reaction mixture was diluted with saturated sodium acetate solution and extracted with ethyl acetate. The extract was washed with water, dried (sodium sulfate) and concentrated. The residue was crystallized from isopropyl acetate to give 1.98 g ethyl (S)-8-(benzylthio)-10-(2,6-dimethyl-4-pyridinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate, yellow solid, m.p. 175°-178° C.