Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]4[C:24](=[O:25])[N:23]5[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[C:22]5=[N:21][C:20]=4[CH3:31])[CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[C:32](OC(=O)C)(=[O:34])[CH3:33]>C(O)(=O)C>[C:32]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=2)[C:6]([CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]3[C:24](=[O:25])[N:23]4[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[C:22]4=[N:21][C:20]=3[CH3:31])[CH2:13][CH2:12]2)=[N:7]1)(=[O:34])[CH3:33]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1nc2c(C)cccn2c(=O)c1CCN1CCC(c2n[nH]c3cc(F)ccc23)CC1
Solvent: CC(=O)O
Product: CC(=O)n1nc(C2CCN(CCc3c(C)nc4c(C)cccn4c3=O)CC2)c2ccc(F)cc21
Reaction time: 2 h
Yield: 95.3 %

Procedure:
A mixture of 3.2 parts of 3-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethyl]-2,9-dimethyl-4H-pyrido[1,2-a]pyrimidin-4-one, 27 parts of acetic anhydride and 15.7 parts of acetic acid was stirred for 2 hours at reflux temperature. The reaction mixture was evaporated and the residue was poured into 100 parts of water. After basifying with NH4OH, the product was extracted with dichloromethane. The extract was dried, filtered and evaporated and the residue was crystallized from 2-propanol, yielding 3.3 parts (95.3%) of 3-[2-[4-(1-acetyl-6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethyl]-2,9-dimethyl-4H-pyrido[1,2-a]pyrimidin-4-one; mp. 210.3° C. (compound 46). All other compounds listed in tables 1 to 3 were obtained following methods of preparation analogous to those described in examples 2 to 6, as is indicated in the column headed by Ex. No.
Reaction SMILES: Br[C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:5]2=[N:4][C:3]=1[CH2:17][CH2:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=1.CC1(C)C(C)(C)OB([C:37]2[CH:42]=[CH:41][C:40]([N:43]3[CH:47]=[N:46][C:45](=[O:48])[N:44]3[CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])=[CH:39][CH:38]=2)O1>>[O:14]1[CH2:15][CH2:16][N:11]([C:10]2[C:5]3[N:6]([C:2]([C:37]4[CH:38]=[CH:39][C:40]([N:43]5[CH:47]=[N:46][C:45](=[O:48])[N:44]5[CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])=[CH:41][CH:42]=4)=[C:3]([CH2:17][CH2:18][C:19]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[N:20]=4)[N:4]=3)[N:7]=[CH:8][CH:9]=2)[CH2:12][CH2:13]1
Reactant: CC1(C)OB(c2ccc(-n3cnc(=O)n3COCC[Si](C)(C)C)cc2)OC1(C)C
Reactant: Brc1c(CCc2ccc3ccccc3n2)nc2c(N3CCOCC3)ccnn12
Product: C[Si](C)(C)CCOCn1c(=O)ncn1-c1ccc(-c2c(CCc3ccc4ccccc4n3)nc3c(N4CCOCC4)ccnn23)cc1

Procedure:
Compound 46a was subjected to Suzuki coupling conditions with compound 52d using the procedures described in Example 38, step A, to obtain compound 52e as a white solid. Mass Spectrum (LCMS, ESI pos.) Calcd. For C34H39N9O3Si: 649.3 (M+H). Found 649.2.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([O:13][C:14](=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][S:22]([CH3:25])(=[O:24])=[O:23])[CH3:12].[C:27]([Si:31]([O:34][CH:35]([C:41]1[CH:46]=[CH:45][C:44]([CH2:47]I)=[CH:43][CH:42]=1)[CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])([CH3:33])[CH3:32])([CH3:30])([CH3:29])[CH3:28]>C1COCC1>[CH2:11]([O:13][C:14](=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][S:22]([CH2:25][CH2:47][C:44]1[CH:43]=[CH:42][C:41]([CH:35]([O:34][Si:31]([C:27]([CH3:28])([CH3:30])[CH3:29])([CH3:32])[CH3:33])[CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[CH:46][CH:45]=1)(=[O:23])=[O:24])[CH3:12]
Reactant: CCCCCC(O[Si](C)(C)C(C)(C)C)c1ccc(CI)cc1
Reactant: CCOC(=O)CCCCCCNS(C)(=O)=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCC(O[Si](C)(C)C(C)(C)C)c1ccc(CCS(=O)(=O)NCCCCCCC(=O)OCC)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 32.5 %

Procedure:
Sodium bis(trimethylsilyl)amide (1.0 mL of a 1.0 M solution in THF, 1.00 mmol) was added to a solution of the sulfonamide 4 (220 mg, 0.88 mmol) in THF (2.2 mL) at 0° C. The reaction was warmed to room temperature and a solution of the iodide 9 (432 mg, 1.00 mmol) in THF (3.0 mL) was added. The reaction was stirred at room temperature for 16 h, quenched with saturated aqueous NH4Cl and extracted with EtOAc. The organic portion was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. FCC (silica gel, 4:1 hex/EtOAc) gave 159 mg (29%) of the silyl ether 10 as a light yellow viscous oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([CH3:22])=[N:11][N:12]([CH:19]3[CH2:21][CH2:20]3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.C(N(CC)CC)C.O(S(C)(=O)=O)S(C)(=O)=O.[CH3:40][O:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46][NH2:47])=[CH:44][CH:43]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:47][CH2:46][C:45]2[CH:48]=[CH:49][C:42]([O:41][CH3:40])=[CH:43][CH:44]=2)[C:9]2[C:10]([CH3:22])=[N:11][N:12]([CH:19]3[CH2:21][CH2:20]3)[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1
Reactant: COc1ccc(CN)cc1
Reactant: CCOC(=O)c1c(C(O)c2ccc(Cl)cc2)c(C)nn1C1CC1
Agent: CS(=O)(=O)OS(C)(=O)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)c1c(C(NCc2ccc(OC)cc2)c2ccc(Cl)cc2)c(C)nn1C1CC1
Reaction time: 0.5 h
Yield: 77.3 %

Procedure:
To a stirred solution of ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-cyclopropyl-3-methyl-1H-pyrazole-5-carboxylate (Step 23.5) (2.12 g, 6.33 mmol) and triethylamine (4.41 mL, 31.7 mmol) in CH2Cl2 (4 mL) under Ar was added Ms2O (2.206 g, 12.66 mmol) at −10° C. The reaction mixture was stirred for 30 min at this temperature. 4-Methoxybenzylamine (0.827 ml, 6.33 mmol) was added at 30° C. After 15 h at rt, the reaction mixture was quenched with a saturated aqueous solution of NaHCO3 (100 mL), and extracted with CH2Cl2 (2×100 mL). The combined organic layers were washed with a saturated aqueous solution of NaHCO3 (100 mL), dried (Na2SO4) and evaporated. The crude material was purified by silica gel column chromatography (Hex/EtOAc 5-20%) to afford the title product (2.22 g, 4.89 mmol, 77% yield) as a colorless oil. tR: 1.12 min (LC-MS 2); ESI-MS: 454 [M+H]+ (LC-MS 2); Rf=0.85 (hexane/EtOAc 1:1).
Reaction SMILES: [C:1]([O:8][CH2:9][CH2:10][O:11][C:12](=[O:16])[C:13]([CH3:15])=[CH2:14])(=[O:7])[CH2:2][CH2:3][C:4]([O-:6])=O.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:39][CH2:40][CH2:41][C:42]1[CH:47]=[CH:46][C:45]([OH:48])=[CH:44][CH:43]=1>CN(C)C=O.C(OCC)(=O)C>[OH:48][C:45]1[CH:46]=[CH:47][C:42]([CH2:41][CH2:40][NH:39][C:4]([CH2:3][CH2:2][C:1]([O:8][CH2:9][CH2:10][O:11][C:12](=[O:16])[C:13]([CH3:15])=[CH2:14])=[O:7])=[O:6])=[CH:43][CH:44]=1
Reactant: NCCc1ccc(O)cc1
Reactant: C=C(C)C(=O)OCCOC(=O)CCC(=O)[O-]
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C=C(C)C(=O)OCCOC(=O)CCC(=O)NCCc1ccc(O)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 92.3 %

Procedure:
10.0 Gram (43.4 mmol) of 2-methacryloyloxyethyl succinate, 10.0 g (52.1 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 7.04 g (52.1 mmol) of 1-hydroxy-1H-benzotriazole were dissolved in 120 mL of N,N-dimethylformamide, and the resulting solution was cooled to 0° C. in a nitrogen stream and stirred for 0.5 hours. Subsequently, 5.95 g (43.4 mmol) of 4-(2-aminoethyl)phenol was added thereto, and the mixture was stirred at room temperature for 1 hour and further stirred at 60° C. for 4 hours. After adding 200 mL of ethyl acetate, the organic layer was washed, in sequence, three times with an aqueous saturated sodium hydrogencarbonate solution and twice with water and dried over sodium sulfate. The solvent was concentrated to obtain 14.0 g of 2-methacryloyloxyethyl 3-(4-hydroxyphenethylcarbamoyl)propanoate as a brown oil. Thereafter, 6.7 g (19.18 mmol) of this oil and 7.28 g (23.02 mmol) of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonyl difluoride were dissolved in 100 mL of tetrahydrofuran (THF), and the resulting solution was cooled to 0° C. Thereto, 2.91 g of triethylamine was added dropwise over 0.3 hours, and the obtained reaction solution was stirred at 0° C. for 1 hour and further stirred at room temperature for 12 hours. Thereafter, 50 mL of triethylamine and 5.72 g (38.36 mmol) of trifluoromethanesulfonamide were added thereto, and the mixture was stirred at 50° C. for 4 hours. After adding 200 mL of ethyl acetate, the organic layer was washed, in sequence, twice with dilute hydrochloric acid and twice with water and dried over sodium sulfate. The solvent was concentrated, and the residue was purified by column chromatography (SiO2, ethyl acetate) to obtain 14.4 g of a brown oil. This brown oil was dissolved in 50 mL of methanol, and 5.64 g of triphenylsulfonium bromide was added thereto, followed by stirring at room temperature for 3 hours. After adding 200 mL of chloroform, the organic layer was washed with water, the solvent was concentrated, and the residue was purified by column chromatography (SiO2, ethyl acetate/methanol=6/1), as a result, 8.16 g of a brown transparent oily compound was obtained. 1H-NMR (300 MHz, CDCl3) δ 1.93 (s, 3H), 2.45 (t, 2H), 2.65 (t, 2H), 2.82 (t, 2H), 3.44 (q, 2H), 4.32 (bs, 4H), 5.58 (s, 1H), 6.08 (t, 1H), 6.11 (s, 1H), 7.15 (d, 2H), 7.23 (d, 2H), 7.62-7.79 (m, 15H), 19F-NMR (300 MHz, CDCl3) δ −78.7 (s, 3F), −107.8 (m, 2F), −112.4 (t, 2F), −118.0 (m, 2F).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.[Br:15][C:16]1[C:17](F)=[C:18]2[C:24]([NH:25][C:26](=[O:34])[C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[N:29][CH:28]=3)=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1>CCCCO>[Br:15][C:16]1[C:17]([N:1]2[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)=[C:18]2[C:24]([NH:25][C:26](=[O:34])[C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[N:29][CH:28]=3)=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1
Reactant: Cc1cncc(C(=O)Nc2c[nH]c3ncc(Br)c(F)c23)c1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCNC1
Solvent: CCCCO
Product: Cc1cncc(C(=O)Nc2c[nH]c3ncc(Br)c(N4CCC[C@@H](NC(=O)OC(C)(C)C)C4)c23)c1
Temperature: 160 °C
Reaction time: 24 h
Yield: 31 %

Procedure:
(R)-tert-Butyl piperidin-3-ylcarbamate (172 mg, 0.859 mmol) was added to N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylnicotinamide (100 mg, 0.286 mmol) in n-BuOH (3 mL), and the reaction was stirred at 160° C. for 24 hours in a sealed tube. The reaction was concentrated to dryness, and then the residue was purified by chromatography (SP4, 25M, water/ACN 90/10 to 10/90, 30CV) to yield (R)-tert-butyl 1-(5-bromo-3-(5-methylnicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (47 mg, 31.0% yield) as a solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][OH:11])=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[H][H]>C(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:7]=1
Reactant: OCC#Cc1ccc(Br)cc1
Reactant: [H][H]
Solvent: Cc1ccccc1
Solvent: CCO
Product: OCCCc1ccc(Br)cc1
Yield: 81.1 %

Procedure:
To a solution under inert gas of 36.4 g of 3-(4-bromophenyl)-2-propynol (stage A) in 200 ml of ethanol at 5% of toluene, is added 200 ml of toluene, 7.9 g of Wilkinson's reagent and hydrogen at 1900 mbar for 5 hours. It is evaporated at reduced pressure until the obtainment of 45.9 g of raw product that is purified by chromatography on silica by eluting with the compound CH2Cl2/AcOEt 95/5. 30.1 g of expected product is obtained.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:15][CH2:16][CH2:17][N:18]([CH2:27][CH2:28][OH:29])[C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[OH:15][CH2:16][CH2:17][N:18]([CH2:27][CH2:28][OH:29])[C:19]1[CH:26]=[CH:25][C:22]([C:23]2[NH:6][C:4](=[O:5])[C:3]3[C:7]([O:13][CH3:14])=[CH:8][C:9]([O:11][CH3:12])=[N:10][C:2]=3[N:1]=2)=[CH:21][CH:20]=1
Reactant: COc1cc(OC)c(C(N)=O)c(N)n1
Reactant: O=Cc1ccc(N(CCO)CCO)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(N(CCO)CCO)cc3)nc2n1
Temperature: 150 °C
Yield: 10.2 %

Procedure:
To a solution of 2-amino-4,6-dimethoxy-nicotinamide (300 mg, 1.52 mmol) and 4-(bis-(2-hydroxyethyl)amino)-benzaldehyde (318 mg, 1.52 mmol) in N,N-dimethylacetamide (10 mL) were added NaHSO3 (297 mg, 1.67 mmol) and p-TSA (376 mg, 1.98 mmol) and the reaction mixture was heated at 150° C. for 4 h, cooled to room temperature, and concentrated under reduced pressure. The residue was diluted with water and the solid was filtered off to give the crude product. The crude product was purified by column chromatography to give 2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one (60 mg, 10%). Selected data: MS (ES) m/z: 387.05; MP 277-279° C.
Reaction SMILES: O=[C:2]1[NH:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)=[C:4]([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[O:3]1.P(Cl)(Cl)([Cl:25])=O.N1C=CC=CC=1>O>[Cl:25][C:2]1[O:3][C:4]([CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[N:6]=1
Reactant: COC(=O)CCc1oc(=O)[nH]c1-c1ccc(C(F)(F)F)cc1
Reactant: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Solvent: O
Product: COC(=O)CCc1oc(Cl)nc1-c1ccc(C(F)(F)F)cc1
Temperature: 102.5 °C
Reaction time: 1 h

Procedure:
A mixture of methyl 3-[2-oxo-4-(4-trifluoromethylphenyl)-4-oxazolin-5-yl]propionate (3.90 g), phosphorus oxychloride (11.5 g) and pyridine (0.98 g) was heated to 100-105° C. and stirred for 1 hour. The reaction mixture was added dropwise to heated water (100 ml) of 30 ° C. and extracted with ethyl acetate (150 ml×2). The organic layer was washed with a saturated aqueous solution of sodium chloride (100 ml), and dried over anhydrous magnesium sulfate. The organic layer was concentrated, the residue was subjected to silica gel column chromatography, and methyl 2-chloro-4-(4-trifluoromethylphenyl)-5-oxazolepropionate was obtained as a yellow oil (2.66 g, 64%) from an ethyl acetate-hexane (1:4, v/v)-eluted fraction.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH2:10][CH3:11])[C:4]=1[C:12]1[C:13](=[O:31])[N:14]([CH3:30])[N:15]=[C:16]([CH2:28][OH:29])[C:17]=1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:41][O:42][CH2:43]Cl.C(=O)([O-])O.[Na+]>C1COCC1>[CH2:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH2:10][CH3:11])[C:4]=1[C:12]1[C:13](=[O:31])[N:14]([CH3:30])[N:15]=[C:16]([CH2:28][O:29][CH2:41][O:42][CH3:43])[C:17]=1[S:18]([C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)(=[O:20])=[O:19])[CH3:2]
Reactant: CCc1cc(C)cc(CC)c1-c1c(S(=O)(=O)c2ccc(C)cc2)c(CO)nn(C)c1=O
Reactant: COCCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCc1cc(C)cc(CC)c1-c1c(S(=O)(=O)c2ccc(C)cc2)c(COCOC)nn(C)c1=O
Temperature: 25 °C
Yield: 79.9 %

Procedure:
To a solution of 4-(2,6-diethyl-4-methylphenyl)-6-hydroxymethyl-5-(4-methylphenylsulfonyl)-2-methyl-3(2H)-pyridazinone (2.40 g, 5.45 mmol) and diisopropylethylamine (10 ml, 57.4 mmol) in THF (20 ml) was added chloromethyl methyl ether (2.4 ml, 31.6 mmol), and refluxed for 4 hours. After the reaction solution was cooled to room temperature, to the reaction solution was added saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate 2 times. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give 2.11 g of 4-(2,6-diethyl-4-methylphenyl)-6-methoxymethoxymethyl-5-(4-methylphenylsulfonyl)-2-methyl-3(2H)-pyridazinone (yield: 80%) as solid.
Reaction SMILES: [O:1]([CH:13]([CH3:15])[CH3:14])[C@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4].[C:16](O)(=[O:24])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].C1C(CCCCC(N)=O)SSC1>CC(=O)CC>[C:16]([O:12][CH2:11][C@H:9]1[O:10][C@H:2]([O:1][CH:13]([CH3:15])[CH3:14])[C@H:3]([OH:4])[C@@H:5]([OH:6])[C@@H:7]1[OH:8])(=[O:24])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCCC(=O)O
Reactant: CC(C)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Agent: NC(=O)CCCCC1CCSS1
Solvent: CCC(C)=O
Product: CCCCCCCC(=O)OC[C@H]1O[C@H](OC(C)C)[C@H](O)[C@@H](O)[C@@H]1O
Reaction time: 48 h
Yield: 68.9 %

Procedure:
To a stirred solution of isopropyl α-D-glucopyranoside (1.1 g, 5 mmol) and octanoic acid (0.9 g, 6.25 mmol) in 100 ml 2-butanone was added immobilized lipase (0.5 g Lipozyme™, see example 8). Stirring was continued at 60° C. for 48 hours. The enzyme was removed by filtration and the solvent was removed in vacuo followed by chromatography yielding 1.2 g (70%) of the product 1H NMR (400 MHz, CDCl3) δ: 0.88 (t, J=6.7 Hz, 3H); 1.19 (d, J=6.1 Hz, 3H); 1.24 (d, J=6.2 Hz, 3H); 1.28 (m, 8H); 1.62 (m, 2H); 2.34 (m, 2H); 3.35 (t, J=9.4 Hz, 1H); 3.50 (dd, J=4.0 and 9.5 Hz, 1H); 3.73 (t,J=9.3 Hz, 1 H); 3.85 (m, 1H); 3.92 (m, 1H) 4.35 (m, 2H); 4.96 (d, J=3.9 Hz, 1H).
Reaction SMILES: F[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[CH:12]=1.[Na].[CH3:22][SH:23].CN(C=O)C>O>[CH3:22][S:23][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[CH:12]=1
Reactant: CS
Reactant: Fc1cnccc1-c1cc2cc(C(F)(F)F)ccc2o1
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: CSc1cnccc1-c1cc2cc(C(F)(F)F)ccc2o1
Yield: 95 %

Procedure:
A mixture of 0.30 g of 3-fluoro-4-[5-(trifluoromethyl)benzofuran-2-yl]pyridine, 75 mg of methyl mercaptan sodium salt and 4 ml of DMF was stirred under ice-cooling for 1 hour. To this mixture was added 37 mg of methyl mercaptan sodium salt, and the mixture was stirred under ice-cooling for further 1 hour. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layers were combined and washed with water and saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.31 g of 3-methylthio-4-[5-(trifluoromethyl)benzofuran-2-yl]pyridine (hereinafter, referred to as “Present Active Compound 11”).
Reaction SMILES: [N:1]1([S:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[NH2:32]>>[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[NH:32][C:18](=[O:19])[C:17]1[CH:21]=[CH:22][C:14]([S:11]([N:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3][CH2:2]2)(=[O:12])=[O:13])=[CH:15][CH:16]=1
Reactant: O=C(O)c1ccc(S(=O)(=O)N2CCCc3ccccc32)cc1
Reactant: Nc1nc2ccccc2s1
Product: O=C(Nc1nc2ccccc2s1)c1ccc(S(=O)(=O)N2CCCc3ccccc32)cc1

Procedure:
4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)benzoic acid (1) (100 mg, 0.32 mmol) was treated with benzo[d]thiazol-2-amine (39 mg, 0.26 mmol) using method B. The residue was purified using flash chromatography eluting with 0-20% EtOAc in hexanes to give N-(benzo[d]thiazol-2-yl)-4-(3,4-dihydroquinolin-1(2H)-ylsulfonyl)benzamide as an off-white solid. Yield: 29 mg (25%). 1H-NMR: 8.22 (d, J=8.5 Hz, 2H), 8.02 (d, J=8.0 Hz, 1H), 7.73 (d, J=8.5 Hz, 2H), 7.62 (d, J=8.0 Hz, 1H), 7.50-7.45 (m, 1H), 7.37-7.32 (m, 1H), 7.24-7.19 (m, 1H), 7.14-7.08 (m, 2H), 3.84-3.80 (m, 2H), 2.44 (t, J=7.0 Hz, 2H), 1.66-1.58 (m, 2H).
Reaction SMILES: [N:1]([CH2:4][S:5]([CH3:8])(=[O:7])=[O:6])=[C:2]=[O:3].[N+:9](=[C:11]1[C:15]([CH:16]=[CH:17][C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)=[N:14][CH:13]=[N:12]1)=[N-:10]>CS(C)=O>[CH3:8][S:5]([CH2:4][N:1]1[C:2](=[O:3])[N:12]2[CH:13]=[N:14][C:15](/[CH:16]=[CH:17]/[C:18]3[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=3)=[C:11]2[N:9]=[N:10]1)(=[O:7])=[O:6]
Reactant: CS(=O)(=O)CN=C=O
Reactant: N#Cc1ccc(C=CC2=NC=NC2=[N+]=[N-])cc1
Solvent: CS(C)=O
Product: CS(=O)(=O)Cn1nnc2c(/C=C/c3ccc(C#N)cc3)ncn2c1=O
Reaction time: 8 h
Yield: 3.2 %

Procedure:
Isocyanato(methylsulfonyl)methane (440 mg, 3.25 mmol) was added dropwise in the dark under nitrogen to a stirred suspension of E)-4-(2-(4-diazo-4H-imidazol-5-yl)vinyl)benzonitrile (600 mg, 2.71 mmol) in DMSO (6 mL) and the mixture was stirred overnight. The resulting solution was poured into ice and the precipitate was filtered and washed successively with water, ethyl acetate and diethyl ether. The crude product was dried under vacuum and was absorbed on silica and purified by flash chromatography using DCM:MeCN (90:10) as eluent to give the pure title compound as a bright yellow solid (31 mg, 3% yield). δH (DMSO d6): 8.95 (1H, s), 7.95-7.97 (2H, d, J=8.6), 7.84-7.87 (2H, d, J=8.6), 7.75 (2H, s), 5.76 (2H, s), 3.16 (3H, s).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:5]=[CH:4][N:3]=1.[CH2:15]([OH:18])[C:16]#[CH:17].[H-].[Na+].O>CN(C)C=O>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:7]=[C:2]([O:18][CH2:15][C:16]#[CH:17])[N:3]=[CH:4][N:5]=2)=[CH:9][CH:10]=1
Reactant: Fc1ccc(-c2cc(Cl)ncn2)cc1
Reactant: C#CCO
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: C#CCOc1cc(-c2ccc(F)cc2)ncn1
Temperature: 25 °C
Reaction time: 9 h
Yield: 68.9 %

Procedure:
In 7 ml of N,N-dimethylformamide were dissolved 199 mg of 4-chloro-6-(4-fluorophenyl)pyrimidine and 64 mg of 2-propyn-1-ol, to which 46 mg of sodium hydride (60% in oil) was added, followed by stirring at room temperature for 9 hours. The reaction mixture was then poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The resulting residue was subjected to silica gel column chromatography to give 150 mg of 4-(4-fluorophenyl)-6-(2-propynyloxy)pyrimidine (the present compound (58)).
Reaction SMILES: C([O:3][C:4]1[C:5](=O)[CH:6]([C:10](=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:8][CH:9]=1)C.[CH3:18][NH:19][NH2:20]>C(O)(=O)C>[CH3:18][N:19]1[C:5]2[C:4](=[O:3])[CH2:9][CH2:8][CH2:7][C:6]=2[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:20]1
Reactant: CNN
Reactant: CCOC(=O)C(=O)C1CCC=C(OCC)C1=O
Solvent: CC(=O)O
Product: CCOC(=O)c1nn(C)c2c1CCCC2=O
Temperature: 25 °C
Reaction time: 6 h
Yield: 63 %

Procedure:
30 g (0.125 mol) of ethyl (3-ethoxy-2-oxocyclohex-3-en-1-yl)(oxo)acetate were dissolved in 150 mL of glacial acetic acid and 6.5 mL of methylhydrazine were added. The mixture was stirred at room temperature for 6 hours. The solvent was then evaporated and the crude redissolved with water, the solution made basic with 30% NH4OH and extracted with chlorform. The organic layer was then dried over Na2SO4 and concentrated. The residue was chromatographed on a silica gel column (eluant: chloroform) and crystallized from a mixture n-hexane/diethyl ether (TLC chloroform; 63% yield as a white solid).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([S:8]([CH3:10])=O)[C:5]([C:11]#[N:12])=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:3]=1.SC[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:3]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:5]([C:11]#[N:12])=[C:6]([S:8][CH2:10][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[N:7]=1
Reactant: SCCc1ccccn1
Reactant: CS(=O)c1nc(N)nc(-c2ccccc2)c1C#N
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: N#Cc1c(SCCc2ccccn2)nc(N)nc1-c1ccccc1

Procedure:
From 2-amino-4-methanesulfinyl-6-phenyl-pyrimidine-5-carbonitrile, 2-mercaptoethylpyridine and DBU in DME. ES-MS m/e (%): 334 (M+H+, 100).