Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](Cl)(=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8][S:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12](Cl)=[O:13].[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=1>ClCCl.N1C=CC=CC=1>[CH3:28][C:24]1[CH:23]=[C:22]([NH:21][C:1](=[O:19])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[S:8][S:9][C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=2)=[O:13])[CH:27]=[CH:26][CH:25]=1
Reactant: O=C(Cl)c1ccccc1SSc1ccccc1C(=O)Cl
Reactant: Cc1cccc(N)c1
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1cccc(NC(=O)c2ccccc2SSc2ccccc2C(=O)Nc2cccc(C)c2)c1
Yield: 42 %

Procedure:
This compound was prepared according to the general method of Example 77 using 2,2'-dithiobisbenzoyl chloride (2.00 g, 5.83 mmol) in 50 mL of dichloromethane and m-toluidine (1.24 g, 11.6 mmol) in 10 mL of pyridine. The crude product was recrystallized from ethyl ether-ethyl acetate to yield 1.18 g of the title compound, mp 193-195° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5](Cl)=[N:6][CH:7]=1.O.[NH2:11][NH2:12]>CCO>[Br:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5]([NH:11][NH2:12])=[N:6][CH:7]=1
Reactant: NN
Reactant: Cc1cc(Cl)ncc1Br
Solvent: CCO
Solvent: O
Product: Cc1cc(NN)ncc1Br
Temperature: 120 °C
Reaction time: 8 h
Yield: 53 %

Procedure:
Combined 5-bromo-2-chloro-4-methylpyridine (15.0 g, 72.46 mmol) and EtOH (60 mL) and added hydrazine hydrate (85%, 45 mL) and stirred at 120° C. overnight. The reaction mixture was concentrated to give a residue which was extracted with EtOAc (50 mL×2) and water (50 mL×2). Then combined organic layers were extracted with brine, dried over Na2SO4 to and concentrated to give a residue which was purified by flash chromatography (petroleum ether: EtOAc=10:1 to 1:5) to give the title compound (7.8 g, 53%).
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[C:4]([NH:11][C:12]([C:14]2[N:15]=[C:16]([CH3:19])[S:17][CH:18]=2)=[O:13])[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.[NH:32]1[C:40]2[C:35](=[CH:36][C:37](B(O)O)=[CH:38][CH:39]=2)[CH:34]=[CH:33]1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[NH:32]1[C:40]2[C:35](=[CH:36][C:37]([C:2]3[CH:10]=[C:9]4[C:5]([CH:6]=[N:7][NH:8]4)=[C:4]([NH:11][C:12]([C:14]4[N:15]=[C:16]([CH3:19])[S:17][CH:18]=4)=[O:13])[CH:3]=3)=[CH:38][CH:39]=2)[CH:34]=[CH:33]1
Reactant: Cc1nc(C(=O)Nc2cc(Br)cc3[nH]ncc23)cs1
Reactant: OB(O)c1ccc2[nH]ccc2c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: Cc1nc(C(=O)Nc2cc(-c3ccc4[nH]ccc4c3)cc3[nH]ncc23)cs1
Temperature: 150 °C
Yield: 6.7 %

Procedure:
N-(6-Bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide (50 mg), Pd(dppf)Cl2 (12 mg), 2M sodium carbonate (0.222 ml), 1,4-dioxane (1 ml) and water (1 ml) were added to 1H-indol-5-ylboronic acid (29 mg) in a microwave vial. The vial was sealed and heated under microwave irradiation at 150° C. for 15 min. The reaction mixture was extracted with DCM (2×20 ml) and then separated, combined organic layers were evaporated to dryness. The residue was dissolved in methanol:DMSO (1 ml, 1:1) and purified by mass directed preparative HPLC (Method A) to give title compound (3.7 mg).
Reaction SMILES: [NH2:1][C:2](=[N:13][NH:14][C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=O)[CH2:3][S:4]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=[O:6])=[O:5]>C(O)C>[C:7]1([S:4]([CH2:3][C:2]2[N:1]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[NH:14][N:13]=2)(=[O:6])=[O:5])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: NC(CS(=O)(=O)c1ccccc1)=NNC(=O)c1ccccc1
Solvent: CCO
Product: O=S(=O)(Cc1n[nH]c(-c2ccccc2)n1)c1ccccc1
Temperature: 25 °C
Yield: 75.6 %

Procedure:
93.1 g (0.29 mol) Benzenecarboxylic acid (1-amino-2-benzenesulfonyl-ethylidene)-hydrazide were heated at 200° C. for 30 minutes. The molten mass was then cooled, dissolved in 500 ml hot ethanol and stirred for 15 hous at room temperature. The precipitated crystals were filtered off and dried to yield 65.6 g (75%) 3-benzenesulfonylmethyl-5-phenyl-1H-[1,2,4]triazole with mp. 141-144° C. MS m/e (%): 299 (M+, 100).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([CH:23]2[CH2:28][CH2:27][N:26](C(OCC4C=CC=CC=4)=O)[CH2:25][CH2:24]2)[C:12]3=[O:39])=[CH:4][CH:3]=1>Br.C(O)(=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[C:12]3=[O:39])=[CH:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)N1CCC(n2cnc3c(cc(Cc4ccc(Cl)nc4)c4ccccc43)c2=O)CC1
Agent: Br
Solvent: CC(=O)O
Product: O=c1c2cc(Cc3ccc(Cl)nc3)c3ccccc3c2ncn1C1CCNCC1

Procedure:
A solution of benzyl 4-[6-[(6-chloropyridin-3-yl)methyl]-4-oxobenzo[h]quinazolin-3 (4H)-yl]piperidine-1-carboxylate (0.130 g, 0.241 mmol) in 3 mL of HBr/acetic acid solution (48.0% wt, 264 mmol) was stirred at rt for 3 h. The mixture was concentrated in vacuo and azetroped 3× with toluene. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 404.9 for M+H+: 1H NMR (400 MHz, d6-DMSO) δ 9.07 (d, J=7.7 Hz, 1H), 8.47 (s, 1H), 8.30 (s, 1H), 8.12 (d, J=7.9 Hz, 1H), 8.11 (s, 1H), 7.80-7.66 (m, 3H), 7.37 (d, J=8.3 Hz, 1), 3.64 (s, 2H), 3.65-3.61 (m, 2H), 3.31-3.23 (m, 2H), 2.62-2.52 (m, 2H), 2.26 (d, J=12.5 Hz, 2H).
Reaction SMILES: [Na].[C:2]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[N:12])=[N:9][CH:10]=1)([OH:4])=[O:3].N[CH2:14][CH2:15][SH:16].Cl>O.C(O)C>[C:2]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[S:16][CH2:15][CH2:14][N:12]=2)=[N:9][CH:10]=1)([OH:4])=[O:3]
Reactant: NCCS
Reactant: N#Cc1ccc(C(=O)O)cn1
Agent: Cl
Agent: [Na]
Solvent: CCO
Solvent: O
Product: O=C(O)c1ccc(C2=NCCS2)nc1

Procedure:
Sodium (11 mmol) is added to a flask containing 75 ml of ethanol. As soon as the sodium has dissolved, 10 mmol of 5-carboxy-2-cyanopyridine and 11 mmol of 2-amino-ethanethiol are added and the solution is refluxed for 24 h. The solution is then diluted with 25 ml of water, made acidic (pH=5) with 2N HCl and evaporated. The residue is dissolved in 100 ml of hot chloroform, the salts are filtered off and the filtrate on cooling gives crystals of the title compound, m.p. 234°-235° C.
Reaction SMILES: [F:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:22]=[C:21]3[C:17]([N:18]([CH3:24])[C:19](=[O:23])[NH:20]3)=[C:16](I)[N:15]=2)=[N:6]1.[NH:30]1[CH2:33][CH2:32][CH2:31]1>CN1CCCC1=O>[N:30]1([C:16]2[N:15]=[C:14]([C:7]3[C:8]4[C:9](=[N:10][CH:11]=[CH:12][CH:13]=4)[N:5]([CH2:4][C:3]4[CH:26]=[CH:27][CH:28]=[CH:29][C:2]=4[F:1])[N:6]=3)[N:22]=[C:21]3[C:17]=2[N:18]([CH3:24])[C:19](=[O:23])[NH:20]3)[CH2:33][CH2:32][CH2:31]1
Reactant: C1CNC1
Reactant: Cn1c(=O)[nH]c2nc(-c3nn(Cc4ccccc4F)c4ncccc34)nc(I)c21
Solvent: CN1CCCC1=O
Product: Cn1c(=O)[nH]c2nc(-c3nn(Cc4ccccc4F)c4ncccc34)nc(N3CCC3)c21
Temperature: 150 °C
Yield: 5.2 %

Procedure:
200 mg (0.399 mmol) of the compound obtained in example 107 were dissolved in N-methylpyrrolidone (3 ml) and admixed with 1.00 g (17.514 mmol) of azetidine, and then heated in a microwavable flask with septum in a microwave at 150° C. for 5 h. The mixture was purified by means of preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient). 9 mg of the title compound were obtained (5% of theory).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]([NH:5][C@@H:6]1[C@H:13]([OH:14])[C@H:12]([CH3:15])[O:11][C@@H:8]([O:9][CH3:10])[CH2:7]1)=[O:4].B(F)(F)F.[CH3:22]COCC.[N+](=C)=[N-]>C(Cl)Cl>[F:17][C:2]([F:1])([F:16])[C:3]([NH:5][C@@H:6]1[C@H:13]([O:14][CH3:22])[C@H:12]([CH3:15])[O:11][C@@H:8]([O:9][CH3:10])[CH2:7]1)=[O:4]
Reactant: CCOCC
Reactant: CO[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1
Agent: C=[N+]=[N-]
Agent: FB(F)F
Solvent: ClCCl
Product: CO[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](OC)[C@H](C)O1
Reaction time: 1.5 h
Yield: 85 %

Procedure:
A solution of 2.57 g.; 10 mmoles of methyl 2,3,6-trideoxy-3-trifluoroacetamido-α-L-lyxo-hexopyranoside (II-A) in 45 ml. of dry methylene dichloride was treated at 0° C. with 0.1 ml. of boron trifluoride etherate. While maintaining the temperature at 0°, an excess of diazomethane dissolved in methylene dichloride was added until a faint yellow color persisted. After 90 minutes at 0°, a white solid (polymethylene) was removed by filtration, and the filtrate was washed successively with 10% sodium bicarbonate solution and with water, after which it was dried with anhydrous magnesium sulfate. The residue which was obtained by evaporation was crystallized from ethyl ether-hexane to give pure methyl 2,3,6-trideoxy-3-trifluoroacetamido-4-O-methyl-α-L-lyxo-hexopyranoside (II-B, 2.3 g., 85%): m.p. 137°-138°; [α]D =-150° (c=1, in CHCl3); mass spectrum m/e 271 (M+). The pmr spectrum (CDCl3) showed absorptions at 1.23 (d, CH3 --C-- 5), 3.23 and 3.40 (two s, --OCH3) and 4.70δ (broad s, C--1--H).
Reaction SMILES: [CH3:1][S:2][C:3]1[NH:4][CH:5]=[C:6]([CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[N:15][CH:16]=2)[C:7](=[O:9])[N:8]=1.[CH3:17]I>C1COCC1.[H-].[Na+]>[CH3:17][N:4]1[CH:5]=[C:6]([CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[N:15][CH:16]=2)[C:7](=[O:9])[N:8]=[C:3]1[S:2][CH3:1]
Reactant: CI
Reactant: CSc1nc(=O)c(Cc2cncnc2)c[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CSc1nc(=O)c(Cc2cncnc2)cn1C
Reaction time: 0.5 h
Yield: 48.2 %

Procedure:
2-Methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one (50 mg, 0.213 mmol, 1 eq) was dissolved in dry THF (0.7 ml) and NaH, 60% (24.7 mg, 0.618 mmol, 2.9 eq) was added. After 30 min, the reaction mixture was treated with methyl iodide (133 μl, 2.13 mmol, 10 eq) and was stirred overnight. After overnight the excess NaH was quenched by a slow addition of water, diluted with brine (30 ml) and extracted with Et2O (3×20 ml). Combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated to give a crude residue. Crude residue was purified via Biotage SP-1 Snap Si 10 g; 15 ml/min in the gradient of MeoH in DCM: 1% for 1 CV then from 1-5% for 20 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product 1-methyl-2-methylsulfanyl-5-pyrimidin-5-ylmethyl-1H-pyrimidin-4-one (25.5 mg, yield=47.4%, purity=98%). [M+H]+=249.31 1H NMR (300 MHz; DMSO-d6) δ/ppm 2.49 (s, 3H), 3.53 (s, 3H), 3.58 (s, 2H), 7.80 (s, 1H), 8.72 (s, 2H), 9.03 (s, 1H)
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:9]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:10]>>[C:9](=[O:10])([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Oc1ccccc1
Reactant: O=C(Cl)Oc1ccccc1
Product: O=C(Oc1ccccc1)Oc1ccccc1

Procedure:
Example 1 was repeated at 140° C. using 14.1 g of γ-aluminium oxide spheres SPH-512 from Rhone-Poulenc. After 2 h reaction time the phenol conversion was 15.8%, wherein 0.4 g of phenyl chloroformate and 25.1 g of diphenyl carbonate were formed. The selectivity to give carbonate and phenyl chloroformate was greater than 99%.
Reaction SMILES: F[C:2]1[N:7]=[C:6]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[C:21]([CH:23]5[CH2:26][O:25][CH2:24]5)[CH:22]=4)[N:13]=[CH:12][C:11]=3[CH:10]=[N:9]2)[CH:5]=[CH:4][CH:3]=1.[NH:27]1[CH2:33][CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>>[N:27]1([C:2]2[N:7]=[C:6]([N:8]3[C:16]4[CH:15]=[C:14]([C:17]5[CH:18]=[N:19][CH:20]=[C:21]([CH:23]6[CH2:26][O:25][CH2:24]6)[CH:22]=5)[N:13]=[CH:12][C:11]=4[CH:10]=[N:9]3)[CH:5]=[CH:4][CH:3]=2)[CH2:33][CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1
Reactant: Fc1cccc(-n2ncc3cnc(-c4cncc(C5COC5)c4)cc32)n1
Reactant: C1CNCCNC1
Product: c1cc(N2CCCNCC2)nc(-n2ncc3cnc(-c4cncc(C5COC5)c4)cc32)c1
Yield: 18 %

Procedure:
Following the procedures as described in EXAMPLE 8 and starting with 1-(6-fluoropyridin-2-yl)-6-(5-(oxetan-3-yl)pyridin-3-yl)-1H-pyrazolo[4,3-c]pyridine and 1,4-diazepane, 118 was obtained as an off-white solid (22.8 mg, 18%). 1H NMR (400 MHz, DMSO) δ 9.36-9.33 (s, 1H), 9.18-9.13 (t, J=4.0 Hz, 1H), 9.10-9.05 (s, 1H), 8.68-8.62 (d, J=5.1 Hz, 2H), 8.55-8.50 (s, 1H), 7.74-7.69 (dd, J=13.8, 5.6 Hz, 1H), 7.23-7.18 (d, J=7.7 Hz, 1H), 6.65-6.61 (d, J=8.5 Hz, 1H), 5.07-5.00 (dd, J=8.3, 6.1 Hz, 2H), 4.76-4.69 (t, J=6.3 Hz, 2H), 4.48-4.36 (m, 1H), 3.90-3.83 (t, J=5.8 Hz, 2H), 3.83-3.77 (d, J=5.3 Hz, 2H), 3.01-2.93 (m, 2H), 2.75-2.69 (m, 2H), 1.89-1.83 (m, 2H); MS (ESI) m/z: 428.2 [M+H]+
Reaction SMILES: [F:1][CH:2]([F:29])[O:3][C:4]1[C:5]([O:23][CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[C:6](/[CH:10]=[CH:11]/[C:12]2[N:13]=[C:14]3[N:18]([C:19]=2[C:20]([OH:22])=O)[CH:17]=[CH:16][S:15]3)[CH:7]=[CH:8][CH:9]=1.[S:30]1[C:34]2[CH2:35][CH2:36][CH2:37][C:33]=2[N:32]=[C:31]1[NH2:38].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C1COCC1.CN(C=O)C>[CH3:26][C:25]([CH3:28])([CH3:27])[CH2:24][O:23][C:5]1[C:4]([O:3][CH:2]([F:29])[F:1])=[CH:9][CH:8]=[CH:7][C:6]=1/[CH:10]=[CH:11]/[C:12]1[N:13]=[C:14]2[N:18]([C:19]=1[C:20]([NH:38][C:31]1[S:30][C:34]3[CH2:35][CH2:36][CH2:37][C:33]=3[N:32]=1)=[O:22])[CH:17]=[CH:16][S:15]2
Reactant: CC(C)(C)COc1c(/C=C/c2nc3sccn3c2C(=O)O)cccc1OC(F)F
Reactant: Nc1nc2c(s1)CCC2
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(C)(C)COc1c(/C=C/c2nc3sccn3c2C(=O)Nc2nc3c(s2)CCC3)cccc1OC(F)F

Procedure:
The title compound was prepared according to the general procedure (Method B) by coupling Intermediate 7A (100 mg, 0.236 mmol) with 5,6-dihydro-4H-cyclopenta[d][1,3]thiazol-2-amine (37 mg, 0.260 mmol) in the presence of EDCI hydrochloride (91 mg, 0.472 mmol) and DMAP (26 mg, 0.236 mmol) in a mixture of THF and DMF (1:1, 4 mL) to give 20 mg of the product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 1.07 (s, 9H), 2.42-2.52 (m, 2H), 2.75-2.81 (m, 4H), 3.58 (s, 2H), 7.18 (t, J=76.2 Hz, 1H), 7.20-7.28 (m, 2H), 7.38-7.45 (m, 1H), 7.71 (d, J=6.9 Hz, 1H), 7.84 (d, J=15.9 Hz, 1H), 8.05-8.12 (m, 1H), 8.46-8.53 (m, 1H), 13.03 (br s, 1H); APCI-MS (m/z) 545.53 (MH)+.
Reaction SMILES: [CH3:1][C@H:2]1[C@@H:7]([NH2:8])[CH2:6][CH2:5][O:4][CH2:3]1.CCN(C(C)C)C(C)C.[Cl:18][C:19]1[N:24]=[C:23](Cl)[C:22]([N+:26]([O-:28])=[O:27])=[CH:21][N:20]=1>C1COCC1.CCOC(C)=O>[Cl:18][C:19]1[N:24]=[C:23]([NH:8][C@H:7]2[CH2:6][CH2:5][O:4][CH2:3][C@H:2]2[CH3:1])[C:22]([N+:26]([O-:28])=[O:27])=[CH:21][N:20]=1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1Cl
Reactant: C[C@@H]1COCC[C@@H]1N
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C[C@@H]1COCC[C@@H]1Nc1nc(Cl)ncc1[N+](=O)[O-]
Reaction time: 16 h

Procedure:
To a suspension of 0.24 g of the hydrochloride salt of cis-3-methyl-tetrahydro-2H-pyran-4-amine (WO 2004/041161) and DIEA (1.5 mL) in THF (10 mL) at −78° C. was added 2,4-dichloro-5-nitropyrimidine (0.72 g). The mixture was allowed to slowly reach room temperature and stirred for 16 hours. The mixture was diluted with EtOAc and washed 3 times with brine. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo. Column chromatography (20→40% EtOAc/hexanes) provided 289 mg of the title compound.
Reaction SMILES: [CH3:1][O:2][CH:3]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:4][CH:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16]CC)=[O:15].C(O)C.[OH-].[K+].Cl>CCCCCC>[CH3:1][O:2][CH:3]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:4][CH:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15]
Reactant: CCCCCCC(CC=CCCCCCCCC(=O)OCC)OC
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCCCCC
Solvent: CCO
Product: CCCCCCC(CC=CCCCCCCCC(=O)O)OC
Temperature: 50 °C
Reaction time: 4 h
Yield: 93.3 %

Procedure:
Next, to a 1-l flask equipped with a stirrer, 68.1 g (0.2 mol) of ethyl 12-methoxy-9-octadecenoate, 600 ml of ethanol and 45 g of a 50% aqueous solution of potassium hydroxide were charged, followed by stirring at 50° C. for 4 hours. To the reaction mixture so obtained, hexane was added, followed by neutralization with 3N hydrochloric acid and then washing with saturated saline. After concentration under reduced pressure, the residue was purified by chromatography on a silica gel column, whereby 58.3 g of the title compound (8-d) were obtained (yield: 93%).
Reaction SMILES: S(O[C:9]1[CH:26]=[CH:25][C:24]2[C@@H:23]3[C@H:14]([C@H:15]4[C@@:19]([CH2:21][CH2:22]3)([CH3:20])[CH:18]([OH:27])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]=2[C:10]=1[N+:28]([O-])=O)(C(F)(F)F)(=O)=O.C(N(CC)CC)C.ClCCl>CO.[Pd]>[NH2:28][C:10]1[C:11]2[CH2:12][CH2:13][C@@H:14]3[C@@H:23]([C:24]=2[CH:25]=[CH:26][CH:9]=1)[CH2:22][CH2:21][C@@:19]1([CH3:20])[C@H:15]3[CH2:16][CH2:17][C@@H:18]1[OH:27]
Reactant: C[C@]12CC[C@@H]3c4ccc(OS(=O)(=O)C(F)(F)F)c([N+](=O)[O-])c4CC[C@H]3[C@@H]1CCC2O
Agent: [Pd]
Solvent: CO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@]12CC[C@@H]3c4cccc(N)c4CC[C@H]3[C@@H]1CC[C@@H]2O
Reaction time: 5 h
Yield: 25 %

Procedure:
A solution of 4-nitroestra-1,3,5(10)-trien-3,17-diol 3-O-triflate (2.13 g, 4.74 mmol) in 100 ml of methanol containing triethylamine (6.60 , 4.8 mmol) and 10% Pd/C (430 mg. 20% by weight) was hydrogenated in a Parr apparatus at 16 psi for 5 hr. TLC using 95% dichlormethane 1% methanol showed one major product and 3 minor constituents. The reaction mixture was filtered through Celite and the filtrate was evaporated to dryness. The residue was dissolved in excess dichloromethane and the solution was washed with water. The extract was dried over sodium sulfate and filtered. The filtrate was evaporated to dryness. The residue crystallized from methanol as a cluster of colorless needles of 4-aminoestra-1,3,5(10)-trien-17β-ol; wt. 320 mg. (25% yield), mp 189°-192° C. Mass Spectrum: m/z 271 (M+), 237 (M--H2O+NH2). 1H NMR 7.23-6.51 (m, 3, H1, H2, H3 aromatic) 3.71-3.45 (t, 1, 17H), 2.57-1.23 (m, 18), 0.876 (s, 3, C18CH3).
Reaction SMILES: [CH2:1]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:21]=[C:20](O)[C:19]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:18][N:17]=2)=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].P(Cl)(Cl)([Cl:33])=O>>[CH2:1]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:21]=[C:20]([Cl:33])[C:19]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:18][N:17]=2)=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCOc1ccc(-c2ncc(OCc3ccccc3)c(O)n2)cc1
Reactant: O=P(Cl)(Cl)Cl
Product: CCCCCCCCOc1ccc(-c2ncc(OCc3ccccc3)c(Cl)n2)cc1

Procedure:
Ethyl benzyloxyacetate (B) was obtained by esterifying benzyloxyacetic acid as obtained from benzyl alcohol and chloroacetic acid by a conventional Williamson synthesis. (B) (9.7 g) and 3.7 g of ethyl formate were dissolved in 25 ml of ether, and stirred in the presence of sodium for 2 hours, and ether was distilled away to obtain sodium 2-benzyloxy-2-ethoxycarbonylethylenolate (C). To this compound was added a solution as prepared by dissolving 14.2 g of 4-decyloxybenzamidine hydrochloride (synthesized from 4-decyloxycyanobenzene by a conventional method) in 80 ml of ethanol and adding 1.2 g of sodium, and the mixture was refluxed for 2 hours. The solvent was distilled away to obtained 2-(4-octyloxyphenyl)-4-hydroxy-5-benzyloxypyrimidine (D). (D) (2 g) together with phosphorus oxychloride was refluxed for 3 hours to obtain 2-(4-octyloxyphenyl)-4-chloro-5-benzyloxypyrimidine (E).
Reaction SMILES: N#N.Cl[CH2:4][C:5]1[N:6]=[C:7]([C:10]2([CH3:15])[O:14][CH2:13][CH2:12][O:11]2)[S:8][CH:9]=1.[N+:16]([C:19]1[NH:23][N:22]=[CH:21][CH:20]=1)([O-:18])=[O:17].C([O-])([O-])=O.[K+].[K+].[Br-]>CC(C)=O.CC(=O)OCC.O>[CH3:15][C:10]1([C:7]2[S:8][CH:9]=[C:5]([CH2:4][N:22]3[CH:21]=[CH:20][C:19]([N+:16]([O-:18])=[O:17])=[N:23]3)[N:6]=2)[O:14][CH2:13][CH2:12][O:11]1
Reactant: CC1(c2nc(CCl)cs2)OCCO1
Reactant: O=[N+]([O-])c1ccn[nH]1
Agent: N#N
Agent: O=C([O-])[O-]
Agent: [Br-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: CC1(c2nc(Cn3ccc([N+](=O)[O-])n3)cs2)OCCO1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 4-chloromethyl-2-(2-methyl-[1,3]dioxolan-2-yl)-thiazole (174 mg, 0.79 mmol) in acetone (2.0 mL) was added to a solution of 5-nitro-1H-pyrazole (90 mg, 0.79 mmol) in acetone (2.0 mL). K2CO3 (330 mg, 2.38 mmol) followed by TBA bromide (51 mg, 0.16 mmol) were added and the reaction mixture was stirred at rt overnight. Water (10 mL) and EA (10 mL) were added. The aq. layer was extracted with EA (10 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (1:1 hept-EA) gave the title compound as a pale yellow oil. TLC: rf (1:1 hept-EA)=0.29. LC-MS-conditions 02: tR=0.89 min, [M+H]+=297.23.
Reaction SMILES: C(N(CC)CC)C.[N:8](=[C:10]1[S:14][C:13]([CH3:16])([CH3:15])[N:12]=[C:11]1[CH3:17])[OH:9].[CH3:18][N:19]([S:23][N:24]([CH3:28])[C:25](F)=[O:26])[C:20]([F:22])=[O:21]>C1(C)C=CC=CC=1>[CH3:18][N:19]([S:23][N:24]([CH3:28])[C:25]([O:9][N:8]=[C:10]1[S:14][C:13]([CH3:16])([CH3:15])[N:12]=[C:11]1[CH3:17])=[O:26])[C:20]([F:22])=[O:21]
Reactant: CC1=NC(C)(C)SC1=NO
Reactant: CN(SN(C)C(=O)F)C(=O)F
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CC1=NC(C)(C)SC1=NOC(=O)N(C)SN(C)C(=O)F
Temperature: -50 °C

Procedure:
8.3 ml of triethylamine are added dropwise to a suspension of 8.59 g of 5-oxo-2,2,4-trimethyl-3-thiazoline oxime in a solution of 10.0 g of bis-(N-methyl-N-fluorocarbonylamino)sulfide in 100 ml of absolute toluene, cooled to -50° C. The resulting clear solution is allowed to warm slowly to 0° C. during 11/2 hours, during which time a crystalline product is precipitated. The reaction mixture is poured into ice-cold brine and extracted with ethyl acetate. After drying the organic phase over anhydrous sodium sulfate and evaporating it, the resulting residue is purified by chromatography on silica gel (eluent:ethyl acetate/n-hexane 1:1). Crystallization from ethyl acetate/n-hexane yields 5-oxo-2,2,4-trimethyl-3-thiazoline O-[N-(N-methylfluoroformamidothio)-N-methylcarbamoyl]oxime, m.p. 77°-79° C.
Reaction SMILES: I.CS[C:4](=[NH:18])[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[CH3:19][CH:20](N)[CH:21]([CH3:23])[NH2:22]>C(O)C>[CH3:23][CH:21]1[CH:20]([CH3:19])[NH:18][C:4](=[N:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[NH:22]1
Reactant: CSC(=N)Nc1ccccc1N1CCOCC1
Reactant: CC(N)C(C)N
Agent: I
Solvent: CCO
Product: CC1NC(=Nc2ccccc2N2CCOCC2)NC1C

Procedure:
A mixture of 2-methyl-1-(2-morpholinophenyl)-2-thiopseudourea hydroiodide (7.6 g prepared as described in Example 166), 1,2-dimethylethylenediamine (5.3 g and ethanol (90 ml) was heated under reflux for 70 hours to give a solid which was recrystallised from ethylacetate to give 4-[2-(4,5-dimethyl-2-imidazolidinylideneamino)phenyl]morpholine (m.p. 142°-143° C.).
Reaction SMILES: [N:1]1[C:2]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[NH:16][C:15](=[O:20])[CH2:14][CH2:13]3)=[CH:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.C(C1C(=O)C([Cl:31])=C(Cl)C(=O)C=1C#N)#N.Cl>O1CCOCC1.CC(C)=O>[ClH:31].[N:1]1[C:2]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[NH:16][C:15](=[O:20])[CH:14]=[CH:13]3)=[CH:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12
Reactant: O=C1CCc2cc(-c3cn4ccccc4n3)ccc2N1
Reactant: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Agent: Cl
Solvent: C1COCCO1
Solvent: CC(C)=O
Product: O=c1ccc2cc(-c3cn4ccccc4n3)ccc2[nH]1
Temperature: 70 °C
Yield: 42.4 %

Procedure:
To a suspension of 6-(imidazo[1,2-a]pyridine-2-yl)-3,4-dihydrocarbostyril (5 g) in dioxane (50 ml) was added DDQ (6.47 g) with stirring at 70° C. The reaction mixture was heated for 5 hours with stirring. After completion of reaction, the solvent was evaporated. The residue was extracted by the addition of chloroform and 0.5 N sodium hydroxide. The chloroform layer was washed with 0.5 N sodium hydroxide, washed with water and dried. After evaporating chloroform, the residue obtained was isolated and purified using silica gel column chromatography. Oily product obtained was dissolved in acetone and the solution was adjusted to pH of about 1 with concentrated hydrochloric acid. Crystals which formed were collected by filtration. The crude crystals thus obtained were recrystallized from water to give 2.4 g of 6-(imidazo[1,2-a]pyridine-2-yl)carbostyril monohydrochloride.