Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21](Cl)[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10].[CH:25]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)([CH3:27])[CH3:26]>>[F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([CH:25]([CH3:27])[CH3:26])[CH:33]=3)[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10]
Reactant: CC(C)c1cccc(B(O)O)c1
Reactant: CC(NC(=O)c1coc(Cl)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Product: CC(C)c1cccc(-c2nc(C(=O)NC(C)c3cc(F)c(NS(C)(=O)=O)c(F)c3)co2)c1
Yield: 16.6 %

Procedure:
2-Chloro-oxazole-4-carboxylic acid [1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-amide (50 mg, 0.13 mmol) was reacted with 3-isopropyl phenyl boronic acid (43 mg, 0.26 mmol) to give the title compound (10 mg, 16%) after purification by column chromatography (gradient 12% to 100% EtOAc in n-hexane).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:12]=[C:13]([N:17](C)[C:18](=O)C)[CH:14]=[CH:15][CH:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1>O1CCOCC1.[OH-].[Na+]>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:12]=[C:13]([NH:17][CH3:18])[CH:14]=[CH:15][CH:16]=2)(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: CC(=O)N(C)c1cccc(S(=O)(=O)c2ccc(N)cc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CNc1cccc(S(=O)(=O)c2ccc(N)cc2)c1
Yield: 61.6 %

Procedure:
1.19 g (0.0039 mol) of N-[3-(4-amino-benzenesulphonyl)-phenyl]-N-methyl-acetamide were dissolved in a mixture of 70 ml of dioxane and 70 ml of IN NaOH and heated at reflux for 5 hrs. Subsequently, the organic solvent was distilled off and the residue was made neutral with 1N HCl and extracted with ethyl acetate. The organic phase was washed with water and sat. sodium chloride solution, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel with ethyl acetate/hexane 1:1. The solvent was removed from the product-containing fractions and the residue was recrystallized from ethyl acetate/ether. There was obtained 0.63 g (62%) of [3-(4-amino-benzenesulphonyl) -phenyl]-methylamine as yellow crystals; m.p.: 125-126° C.
Reaction SMILES: [C:1]1([O:11][CH2:12][CH:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C1([O:24][C:25]([O:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=O)C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]1([O:11][CH2:12][CH:13]2[CH2:17][CH2:16][N:15]([C:25]([O:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:24])[CH2:14]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc2c(OCC3CCNC3)cccc2c1
Reactant: CCOC(=O)COC(=O)Oc1ccccc1
Solvent: Cc1ccccc1
Product: CCOC(=O)COC(=O)N1CCC(COc2cccc3ccccc23)C1
Temperature: 60 °C

Procedure:
A solution of 0.20 g (0.88 mmol) of 3-[(1-naphthalenyloxy)methyl]pyrrolidine, prepared in Step 12.2, and 0.35 g (1.5 mmol) of ethyl [(phenyloxycarbonyl)oxy]acetate, prepared in accordance with Example 1.1, in 6 ml of toluene is heated at 60° C. overnight. It is evaporated to dryness and the residue is taken up in a mixture of water, dichloromethane and saturated aqueous sodium hydrogen carbonate solution. The organic phase is decanted, dried over sodium sulfate and evaporated to dryness. The residue is purified by chromatography on a silica gel column, eluting with dichloromethane and then with a 99/1 mixture of dichloromethane and methanol. This gives 0.24 g of product in oil form, which is used as it is in the following step.
Reaction SMILES: N#N.[OH:3][CH:4]([C:6]1[O:7][C:8]([CH2:11][N:12]2[N:16]=[C:15]([NH:17][C:18]([C:20]3[N:21]=[C:22]([CH3:32])[O:23][C:24]=3[C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=3)=[O:19])[CH:14]=[N:13]2)=[CH:9][N:10]=1)[CH3:5]>C(C#N)(C)=O.O=[Mn]=O>[C:4]([C:6]1[O:7][C:8]([CH2:11][N:12]2[N:16]=[C:15]([NH:17][C:18]([C:20]3[N:21]=[C:22]([CH3:32])[O:23][C:24]=3[C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=3)=[O:19])[CH:14]=[N:13]2)=[CH:9][N:10]=1)(=[O:3])[CH3:5]
Reactant: Cc1nc(C(=O)Nc2cnn(Cc3cnc(C(C)O)o3)n2)c(-c2cccc(Cl)c2)o1
Agent: O=[Mn]=O
Agent: CC(=O)C#N
Agent: N#N
Product: CC(=O)c1ncc(Cn2ncc(NC(=O)c3nc(C)oc3-c3cccc(Cl)c3)n2)o1
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 5-(3-chloro-phenyl)-2-methyl-oxazole-4-carboxylic acid {2-[2-(1-hydroxy-ethyl)-oxazol-5-ylmethyl]-2H-[1,2,3]triazol-4-yl}-amide (54 mg, 0.13 mmol) in AcCN (1.5 mL) was treated at rt with MnO2 (91 mg, 0.94 mmol) and the reaction mixture was stirred at rt overnight before being filtered through Celite. The solvent was removed under reduced pressure and the residue was dissolved in EA (10 mL), washed with water (10 mL), and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a white solid. LC-MS-conditions 02: tR=1.06 min; [M+H]+=426.75.
Reaction SMILES: [CH2:1]([PH2:8]=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:10]([O-])([OH:12])=[O:11].S(=O)(=O)(O)O.N>>[N+:10]([C:5]1[CH:6]=[CH:7][C:2]([CH2:1][PH2:8]=[O:9])=[CH:3][CH:4]=1)([O-:12])=[O:11]
Reactant: O=[N+]([O-])O
Reactant: O=[PH2]Cc1ccccc1
Agent: N
Agent: O=S(=O)(O)O
Product: O=[PH2]Cc1ccc([N+](=O)[O-])cc1
Temperature: 55 °C
Reaction time: 2 h

Procedure:
To 1-benzylphosphorane-1-oxide (4.17 g) were added nitric acid (1.7 ml) and sulfuric acid (11 ml) at 0° C., and the mixture was stirred at 50-60° C. for 2 hours. The reaction mixture was added to crushed ice and neutralized with ammonia solution. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated. Under reduced pressure, The residue was separated and purified with column chromatography (ethanol/ethyl acetate=1:4→1:1) to give 1-(4-nitro-benzyl)phosphorane-1-oxide (2.22 g) as yellow crystals.
Reaction SMILES: [C:1]([C:9]1[S:10][CH:11]=[CH:12][CH:13]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[CH2:21](O)[CH2:22][OH:23]>C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:2]1([C:1]2([C:9]3[S:10][CH:11]=[CH:12][CH:13]=3)[O:23][CH2:22][CH2:21][O:8]2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(c1ccccc1)c1cccs1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: c1ccc(C2(c3cccs3)OCCO2)cc1
Reaction time: 35 h

Procedure:
2-Benzoylthiophene (19 g., 0.1 mole), ethylene glycol (11 ml., 0.2 mole), toluene (150 ml.) and p-toluenesulfonic acid (about 0.2 g.) were combined and refluxed for 6 hours. By-product water was collected in a Dean-Stark trap. Tlc (1:8 ethyl acetate:hexane) indicated reaction to be about 40% complete. More ethylene glycol (30 ml.) was added and reflux continued for 35 hours. Reaction was still incomplete. The reaction mixture was diluted with 200 ml. of ether, washed twice with 150 ml. portions of water and concentrated to dryness. The residue was chromatographed on about 500 ml. of silica gel, with 1:8 ethyl acetate:hexane as eluant, monitored by tlc. Faster moving, product containing fractions were combined and evaporated to yield 2-phenyl-2-(2-thienyl)-1,3-dioxolane [8 g., oil, Rf 0.6 (1:8 ethyl acetate:hexane)].
Reaction SMILES: B(F)(F)F.[N:5]1([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:7][C@H:6]1[C:8]([O:10][CH3:11])=[O:9].[CH:22]([OH:25])([CH3:24])[CH3:23].ClCCl>ClCCl>[CH2:15]([O:14][C:12]([NH:5][C@H:6]([C:8]([O:10][CH3:11])=[O:9])[CH2:7][O:25][CH:22]([CH3:24])[CH3:23])=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CC(C)O
Reactant: COC(=O)[C@@H]1CN1C(=O)OCc1ccccc1
Agent: FB(F)F
Solvent: ClCCl
Product: COC(=O)[C@H](COC(C)C)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
16 syringe drops of boron trifluoride diethyletherate (catalyst) was added to a stirred solution of 1-benzyl 2-methyl (2S)-aziridine-1,2-dicarboxylate (0.50 g, 2.1 mmol) in isopropanol/dichloromethane (30 ml, 1:2) at room temperature. The resulting solution was stirred overnight at room temperature. The reaction mixture was diluted with dichloromethane (20 ml), washed with a saturated aqueous sodium bicarbonate (5 ml), water (5 ml), dried over magnesium sulfate, filtered and concentrated to give methyl N-[(benzyloxy)carbonyl]-O-isopropyl-L-serinate as a clear colourless oil, (0.432 g, 68%); 1H NMR Spectrum: (CDCl3) 1.09 (m, 6H), 3.56 (m, 1H), 3.65 (m, 1H), 3.79 (s, 3H), 3.82 (m, 1H), 4.46 (m, 1H), 5.16 (s, 2H), 5.60 (d, 1H), 7.38 (m, 5H).
Reaction SMILES: [CH3:1]I.[CH2:3]1[O:22][C:6]2([C:11]3[CH:12]=[CH:13][C:14]4[C:19]([C:10]=3[S:9](=[O:21])(=[O:20])[NH:8][CH2:7]2)=[CH:18][CH:17]=[CH:16][CH:15]=4)[O:5][CH2:4]1.[OH-].[Na+].O>C(O)(C)C>[CH2:3]1[O:22][C:6]2([C:11]3[CH:12]=[CH:13][C:14]4[C:19]([C:10]=3[S:9](=[O:21])(=[O:20])[N:8]([CH3:1])[CH2:7]2)=[CH:18][CH:17]=[CH:16][CH:15]=4)[O:5][CH2:4]1
Reactant: CI
Reactant: O=S1(=O)NCC2(OCCO2)c2ccc3ccccc3c21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Product: CN1CC2(OCCO2)c2ccc3ccccc3c2S1(=O)=O
Reaction time: 8 h
Yield: 95 %

Procedure:
14.2 gm (0.1 mol) of methyl iodide were added dropwise, while stirring, to a solution of 11.6 gm (0.04 mol) of 2H-naphtho[2,1-e]-1,2-thiazine-4(3H)-one-1,1-dioxide-ethylene ketal in a mixture of 150 ml of isopropanol, 44 ml of 1 N sodium hydroxide and 36 ml of water. The resulting mixture was allowed to stand overnight, and the crystals which separated out were suction-filtered off washed with a mixture of isopropanol an ater (ratio by volume 2:1) and dried in vacuo, yielding 11.6 gm (95% of theory) of 2-methyl-2H-naphtho [2,1-e]-1,2-thiazine-4(3H)-one-1,1-dioxide-ethylene ketal, m.p. 169°-171° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:26][CH2:27][CH3:28])=[O:25])[CH:19]4[OH:29])[C:14]([F:30])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.C[O-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:26][CH2:27][CH3:28])=[O:25])[CH:19]4[OH:29])[C:14]([F:30])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CCNC(=O)C1CCCC(Nc2nc(-c3cn(S(=O)(=O)c4ccc(C)cc4)c4ncc(Cl)cc34)ncc2F)C1O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CCNC(=O)C1CCCC(Nc2nc(-c3c[nH]c4ncc(Cl)cc34)ncc2F)C1O

Procedure:
3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]-N-ethyl-2-hydroxy-cyclohexanecarboxamide, 65c, was treated with NaOMe in MeOH. The product was purified by preparatory HPLC to provide 3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]-N-ethyl-2-hydroxy-cyclohexanecarboxamide as a mixture of stereoisomers. LCMS: 433.35 (M+1).
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C:15]([CH2:16][C@@H:17]([O:31]C(=O)C)[CH2:18][C@@H:19]2[O:27]C(=O)C)=[CH:14][CH2:13]3)[CH2:10][CH2:9]1)[CH2:3][O:4]C(=O)C.[OH-].[Na+]>CO>[CH3:1][C@@H:2]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C:15]([CH2:16][C@@H:17]([OH:31])[CH2:18][C@@H:19]2[OH:27])=[CH:14][CH2:13]3)[CH2:10][CH2:9]1)[CH2:3][OH:4]
Reactant: CC(=O)OC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OC(C)=O)C[C@H](OC(C)=O)[C@]4(C)[C@H]3CC[C@]12C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C[C@H](CO)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C

Procedure:
A solution of (20S)-20-methyl-1α,3β,21-triacetyloxypregn-5-ene in methanol was treated with sodium hydroxide at reflux to produce (20S)-20-methylpregn-5-ene-1α,3β,21-triol.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH2:21][O:22][CH3:23])[CH:14]=3)=[CH:11][C:10]([C:24](O)=[O:25])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.ClC1C=C(N2C(C3C=CC=C(OCCO)C=3)=CC(C([N:51]3[CH2:55][C:54](=[O:56])[NH:53][CH2:52]3)=O)=N2)C=CC=1>>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH2:21][O:22][CH3:23])[CH:14]=3)=[CH:11][C:10]([C:24]([N:51]3[CH2:55][C:54](=[O:56])[NH:53][CH2:52]3)=[O:25])=[N:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CN(C(=O)c2cc(-c3cccc(OCCO)c3)n(-c3cccc(Cl)c3)n2)CN1
Reactant: COCCOc1cccc(-c2cc(C(=O)O)nn2-c2cccc(Cl)c2)c1
Product: COCCOc1cccc(-c2cc(C(=O)N3CNC(=O)C3)nn2-c2cccc(Cl)c2)c1

Procedure:
The preparation of the title compound takes place starting from the compound of Example 117A in analogy to the synthesis of the compound of Example 23. In order to remove the 1,1′,1″-phosphoryltripyrrolidine the product is taken up in a little tetrahydrofuran, water is added to the mixture until a precipitate forms, the tetrahydrofuran is removed in vacuo, and the precipitate is collected by suction filtration, and dried under high vacuum. 10 mg (19% of theory) of the title compound are obtained.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[Si:22](Cl)([C:35]([CH3:38])([CH3:37])[CH3:36])([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Si:22]([O:1][CH:2]1[CH2:3][CH2:4][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:7]1)([C:35]([CH3:38])([CH3:37])[CH3:36])([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)C1CCC(O)CC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C1CCC(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)CC1
Yield: 99 %

Procedure:
The reactant ethyl 4-hydroxycyclohexanecarboxylate (5.4 g, 30.73 mmol) in DCM (100 mL) was treated with DIPEA (16.06 mL, 92.2 mmol), DMAP (4.13 g, 30.80 mmol) and TBDPS-Cl (11.8 mL, 46.1 mmol) at RT for 16 h. After concentrated in vacuum, the residue was purified by CombiFlash on silica gel column using EtOAC/Hexane as eluents to give ethyl 4-(tert-butyldiphenylsilyloxy)cyclohexanecarboxylate 157a, 12.6 g, 99% yield.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:19]=[C:9]2[N:10]=[C:11](S(C)(=O)=O)[N:12]=[C:13]([NH2:14])[N:8]2[N:7]=1.[NH2:20][CH2:21][C@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28]>CC#N>[C:30]([O:29][C:27]([N:23]1[CH2:24][CH2:25][CH2:26][CH:22]1[CH2:21][NH:20][C:11]1[N:12]=[C:13]([NH2:14])[N:8]2[N:7]=[C:6]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)[N:19]=[C:9]2[N:10]=1)=[O:28])([CH3:33])([CH3:32])[CH3:31]
Reactant: CS(=O)(=O)c1nc(N)n2nc(-c3ccco3)nc2n1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CN
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCCC1CNc1nc(N)n2nc(-c3ccco3)nc2n1
Temperature: 25 °C
Yield: 87.9 %

Procedure:
2-Furan-2-yl-5-methanesulfonyl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine (2.5 mmol; see Example 1(a)) was suspended in 20 mL of CH3CN along with 5 mmol of (R)-2-aminomethyl-1-Boc-pyrrolidine (Astatech, Monmouth Junction, N.J.). The reaction mixture was stirred under reflux for 2 hours. It was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with CH2Cl2 and washed with dilute 1% citric acid, brine, dried with Na2SO4 and concentrated under reduced pressure. Purification by chromatography (98% CH2Cl2, 2% MeOH) afforded 880 mg of 2-[(7-amino-2-furan-2-yl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-ylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:28])[C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[N:16]1[C:20]([CH2:21]O)=[N:19][N:18]=[C:17]1[CH2:23][CH2:24][N:25]([CH3:27])[CH3:26].[C:29]1(=[O:39])[NH:33][C:32](=[O:34])[C:31]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:30]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:28])[C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[N:16]1[C:20]([CH2:21][N:33]2[C:32](=[O:34])[C:31]3=[CH:35][CH:36]=[CH:37][CH:38]=[C:30]3[C:29]2=[O:39])=[N:19][N:18]=[C:17]1[CH2:23][CH2:24][N:25]([CH3:26])[CH3:27]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CN(C)CCc1nnc(CO)n1-c1ccc(F)cc1C(=O)c1ccccc1Cl
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN(C)CCc1nnc(CN2C(=O)c3ccccc3C2=O)n1-c1ccc(F)cc1C(=O)c1ccccc1Cl

Procedure:
In the manner given in Example 1B, 2'-chloro-5-fluoro-2-[3-[2-(dimethylamino)ethyl]-5-(hydroxymethyl)-4H-1,2,4-triazol-4-yl]benzophenone in tetrahydrofuran is treated with phthalimide, triphenylphosphine and diethyl azodicarboxylate to give 2'-chloro-5-fluoro-2-[3-[2-(dimethylamino)ethyl]-5-(phthalimidomethyl)-4H-1,2,4-triazol- 4-yl]benzophenone.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=1)[CH3:2].[H][H]>[Pd].C(O)C>[CH2:1]([O:3][C:4](=[O:15])[CH2:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][OH:14])=[CH:11][CH:12]=1)[CH3:2]
Reactant: CCOC(=O)C=Cc1ccc(CO)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CCc1ccc(CO)cc1

Procedure:
3-(4-Hydroxymethylphenyl)acrylic acid ethyl ester (P4, 3 g, 14.5 mmol) and palladium on charcoal (0.3 g) in ethanol (30 mL) was stirred for 4 hours under atmospheric pressure of hydrogen. The reaction mixture was filtered through celite (Diatomaceous Earth) and concentrated to afford the title compound as an oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH3:14][CH:15]1[C:24]2[C:19](=[C:20]([C:25]3[C:26]([CH3:30])=[N:27][NH:28][CH:29]=3)[CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:16]3[CH2:17][CH2:18][C:19]4[C:24](=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]4[C:26]([CH3:30])=[N:27][NH:28][CH:29]=4)[CH:15]3[CH3:14])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Reactant: Cc1n[nH]cc1-c1cccc2c1CCNC2C
Product: Cc1n[nH]cc1-c1cccc2c1CCN(C(=O)c1cc3ncc(Br)cn3n1)C2C

Procedure:
In close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 1-Methyl-5-(3-methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][C:32]([NH2:35])=[N:33][CH:34]=2)O1>>[NH2:35][C:32]1[N:33]=[CH:34][C:29]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]3=[O:20])=[CH:30][N:31]=1
Reactant: CC1(C)OB(c2cnc(N)nc2)OC1(C)C
Reactant: COC(=O)c1cc(C2CC2)c2c(C)c(Cl)ccn2c1=O
Product: COC(=O)c1cc(C2CC2)c2c(C)c(-c3cnc(N)nc3)ccn2c1=O
Yield: 80.6 %

Procedure:
Methyl 8-(2-aminopyrimidin-5-yl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate was prepared according to General Procedure A from methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (100 mg, 0.34 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (90.8 mg, 0.41 mmol). Purification by flash silica column chromatography (DCM:MeOH) (1:0 to 9:1) afforded the title compound as a yellow solid (96 mg, 80%).
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH:8]([CH:11]=O)[C:9]#[N:10])=[CH:6][CH:5]=[CH:4][N:3]=1.O.C(O)(=O)C.C(O)C.[NH2:21][NH2:22]>O1CCOCC1>[Cl:1][C:2]1[C:7]([C:8]2[C:9]([NH2:10])=[N:21][NH:22][CH:11]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: NN
Reactant: N#CC(C=O)c1cccnc1Cl
Solvent: CC(=O)O
Solvent: C1COCCO1
Solvent: O
Product: Nc1n[nH]cc1-c1cccnc1Cl
Temperature: 70 °C
Reaction time: 0.33 h

Procedure:
In a 150 mL sealed tube, added 2-(2-chloropyridin-3-yl)-3-oxopropanenitrile (2.5 g, 14 mmol), water (2.0 mL, 14 mmol), acetic acid (14 mL, 14 mmol), ethanol (28 mL, 14 mmol), 1,4-dioxane (14 mL), and anhydrous hydrazine (0.40 ml, 14 mmol). The mixture was stirred at 70° C. for 20 minutes. The reaction was cooled to RT and concentrated. The concentrate was extracted into EtOAc, washed 1×NaHCO3, 1×H2O, dried over Mg2SO4, filtered through fritted funnel and concentrated. The crude was purified using reverse phase chromatography. The product was extracted into CH2Cl2, washed 1×NaHCO3 1×H2O, dried with Na2SO4, filtered through fritted funnel, concentrated to yield 4-(2-chloropyridin-3-yl)-1H-pyrazol-3-amine as tan solid. MS m/z=195 [M+1]+. Calc'd for C8H7ClN4: 194.62.
Reaction SMILES: C([O:3][C:4]([CH:6]([CH3:28])[CH2:7][CH2:8][N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[C:17]([CH3:18])[C:12]=2[N:11]=[C:10]1[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)=O)C.CO.[CH3:31][NH2:32]>>[CH3:31][NH:32][C:4]([CH:6]([CH3:28])[CH2:7][CH2:8][N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[C:17]([CH3:18])[C:12]=2[N:11]=[C:10]1[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)=[O:3]
Reactant: CN
Reactant: CCOC(=O)C(C)CCn1c(COc2ccc(Cl)cc2)nc2c(C)cccc21
Solvent: CO
Product: CNC(=O)C(C)CCn1c(COc2ccc(Cl)cc2)nc2c(C)cccc21
Temperature: 25 °C
Reaction time: 64 h

Procedure:
In methylamine (40% in water, 20 ml), 1-[3-(ethoxycarbonyl)butyl]-2-[(4-chlorophenoxy)methyl]-4-methylbenzimidazole (1.50 g, 3.7 mmol) was placed. To this mixture 10 ml of methanol were added, to enhance solubility. The resulting mixture was stirred at room temperature for about 64 hours, after which time the reaction mixture was concentrated in vacuo. The residue was taken up in 200 ml of methylene chloride. The organic fraction was washed once with 200 ml of water. The organic fraction was dried over potassium carbonate and the solvents were removed in vacuo to yield 1.61 grams of a dark oil. The crude material was further purified by flash silica gel chromatography, eluting with a gradient of methylene chlor ide to a 1:1 methylene chloride:ethyl acetate mixture. The fractions containing the desired material were combined and concentrated under reduced pressure to yield 510 mg (36%) of the desired title product as a white solid.
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]2[C:8]([N:13]=1)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:2][CH2:3]C.NC1C=NC=CC=1N.C(O)(=O)CCC>>[CH2:1]([C:5]1[NH:6][C:7]2[C:8]([N:13]=1)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:2][CH3:3]
Reactant: CCCCc1nc2ncccc2[nH]1
Agent: Nc1ccncc1N
Solvent: CCCC(=O)O
Product: CCCc1nc2ncccc2[nH]1

Procedure:
The title compound was prepared according to the procedure described for the preparation of 2-butylimidazo[4,5-b]pyridine starting with 3,4-diaminopyridine and butyric acid. Yield: 6.60 g (89%) amorphous solid.
Reaction SMILES: [CH3:1][N:2]([CH3:15])[CH2:3][CH2:4][NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:8])=[O:7].[H-].[Na+].F[C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1.O>CN(C=O)C>[CH3:1][N:2]([CH3:15])[CH2:3][CH2:4][N:5]([C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1)[S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:7])=[O:8]
Reactant: CN(C)CCNS(=O)(=O)c1ccccc1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN(C)CCN(c1ccc([N+](=O)[O-])cc1)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
6.8 g (29.8 mmol) of N-(2-dimethylamino-ethyl)-phenylsulphonamide are dissolved in 100 ml of DMF and combined with 1.3 g (30 mmol) of sodium hydride (55% in oil). The mixture is stirred for one hour at ambient temperature. Then 4.2 g (29.8 mmol) of 4-fluoro-nitrobenzene are added, and stirring is continued for another 16 hours. After the addition of 300 ml of water the mixture is extracted with ethyl acetate. The organic phase is washed with water, dried and evaporated down. The residue is acidified with 1 N hydrochloric acid and washed with ethyl acetate. The aqueous phase is then made basic again with sodium hydroxide solution and extracted with ethyl acetate. The organic phase is dried and evaporated down.