Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: ClC1C=C(Cl)C=CC=1C1C(=O)N(C)C2N(C)C3C(C=2C=1)=CC(C1NN=CC=1C)=CC=3.[F:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[C:57](=[O:58])[N:56]([CH3:59])[C:41]3[N:42]([CH3:55])[C:43]4[C:48]([C:40]=3[CH:39]=2)=[CH:47][C:46]([C:49]2[NH:50][N:51]=[CH:52][C:53]=2[CH3:54])=[CH:45][CH:44]=4)=[CH:34][CH:33]=1.[C:60](Cl)(=[O:65])[C:61]([CH3:64])([CH3:63])[CH3:62]>>[CH3:62][C:61]([CH3:64])([CH3:63])[C:60]([N:51]1[CH:52]=[C:53]([CH3:54])[C:49]([C:46]2[CH:47]=[C:48]3[C:43](=[CH:44][CH:45]=2)[N:42]([CH3:55])[C:41]2[N:56]([CH3:59])[C:57](=[O:58])[C:38]([C:35]4[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=4)=[CH:39][C:40]3=2)=[N:50]1)=[O:65]
Reactant: Cc1cn[nH]c1-c1ccc2c(c1)c1cc(-c3ccc(F)cc3)c(=O)n(C)c1n2C
Reactant: CC(C)(C)C(=O)Cl
Agent: Cc1cn[nH]c1-c1ccc2c(c1)c1cc(-c3ccc(Cl)cc3Cl)c(=O)n(C)c1n2C
Product: Cc1cn(C(=O)C(C)(C)C)nc1-c1ccc2c(c1)c1cc(-c3ccc(F)cc3)c(=O)n(C)c1n2C

Procedure:
The process is carried out as indicated in Example 70 above, with the compound from Example 53, 3-(4-fluorophenyl)-1,9-dimethyl-6-(4-methyl-2H-pyrazol-3-yl)-1,9-dihydropyrido[2,3-b]indol-2-one, and pivaloyl chloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](=[O:19])[CH2:8][C:9]([CH3:18])([CH3:17])[CH:10]2[O:13]C(=O)C)=[CH:5][CH:4]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>ClCCl.CO>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6](=[CH:5][CH:4]=1)[C:7](=[O:19])[CH2:8][C:9]([CH3:17])([CH3:18])[CH:10]2[OH:13]
Reactant: COc1ccc2c(c1)C(OC(C)=O)C(C)(C)CC2=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COc1ccc2c(c1)C(O)C(C)(C)CC2=O
Reaction time: 8 h

Procedure:
To a solution of acetic acid 7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl ester (0.94 g, 3.44 mmol) in dichloromethane (2 mL) and methanol (10 mL) is added K2CO3 (0.48 g, 3.44 mmol) and the mixture is vigorously stirred for 8 hours. Ethyl acetate is added and the mixture is washed twice with water and brine. The aqueous phases are back-extracted once with dichloromethane and the combined organic phase is dried over magnesium sulfate, filtered, and concentrated to afford 6-methoxy-4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-naphthalen-1-one, which is used in the next step without further purification.
Reaction SMILES: [N:1]1(C(OCC2C=CC=CC=2)=O)[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:15]([N:17]1[CH2:34][CH2:33][CH2:32][C@H:18]1[C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:20])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8]>CO.[Pd]>[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([NH:9][C@H:10]([C:15]([N:17]1[CH2:34][CH2:33][CH2:32][C@H:18]1[C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:20])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8]
Reactant: CCCCCCCCCCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCC(=O)N1C(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CCCCCCCCCCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCC(=O)N1
Yield: 77.3 %

Procedure:
1.22 g (2 mmoles) of Z-Glp-Leu-Pro-NH-C10H21 are dissolved in 30 ml of methanol, 0.2 g of a 10% palladium-on-carbon catalyst are added, and hydrogen is bubbled through the mixture for 30 minutes. The catalyst is filtered off, the filtrate is evaporated, and the oily residue is crystallized from n-hexane. The resulting 0.85 g of crude product are recrystallized from 4 ml of ethyl acetate to obtain 0.74 g (77%) of Glp-Leu-Pro-NH-C10H21 ; m.p.: 140°-141° C., Rf4 =0.76, [α]D25 =-71.3° (c=1%, in acetic acid). Amino acid analysis: Glu: 0.97 (1.0), Leu: 1.00 (1.0), Pro: 1.01 (1.0).
Reaction SMILES: Cl[CH2:2][C:3]([C@H:5]1[N:8]([CH:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:7](=[O:28])[C@@H:6]1[C@H:29]([O:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[CH3:30])=[CH2:4].[I-:42].[Na+]>CC(C)=O>[I:42][CH2:2][C:3]([C@H:5]1[N:8]([CH:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:7](=[O:28])[C@@H:6]1[C@H:29]([O:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[CH3:30])=[CH2:4]
Reactant: C=C(CCl)[C@@H]1[C@@H]([C@@H](C)OC(=O)OCc2ccccc2)C(=O)N1C(Cc1ccc(OC)cc1)Cc1ccc(OC)cc1
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: C=C(CI)[C@@H]1[C@@H]([C@@H](C)OC(=O)OCc2ccccc2)C(=O)N1C(Cc1ccc(OC)cc1)Cc1ccc(OC)cc1

Procedure:
To a solution of (3S,4S)-4-(1-chloromethylethenyl)-3-(1-(R)-benzyloxycarbonyloxyethyl)-1-di(p-anisyl)methyl-2-azetidinone (2.24 g) in acetone (25 ml) was added sodium iodide (1.2 g), and the resultant mixture was stirred at room temperature for 5 hours and concentrated in vacuo to make a volume of about 10 ml. The concentrated solution was diluted with benzene (50 ml) and diethyl ether (50 ml), washed successively with 5% sodium bicarbonate and water and dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate in vacuo gave (3S,4S)-4-(1-iodomethylethenyl)-3-(1-(R)-benzyloxycarbonyloxyethyl)-1-di-(p-anisyl)methyl-2-azetidinone.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH3:19])[NH:12][C:11]([CH2:20][O:21][CH2:22][C:23](=[O:30])[CH2:24][C:25](OCC)=[O:26])=[C:10]1[C:31]([O:33][CH2:34][CH3:35])=[O:32].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH3:19])[NH:12][C:11]([CH2:20][O:21][CH2:22][CH:23]([OH:30])[CH2:24][CH2:25][OH:26])=[C:10]1[C:31]([O:33][CH2:34][CH3:35])=[O:32]
Reactant: CCOC(=O)CC(=O)COCC1=C(C(=O)OCC)C(c2cccc(Cl)c2Cl)C(C(=O)OC)=C(C)N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)C1=C(COCC(O)CCO)NC(C)=C(C(=O)OC)C1c1cccc(Cl)c1Cl
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 27.3 %

Procedure:
A solution of ethyl 4{[4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyrid-2-yl]methoxy}acetoacetate (0.99 g) (see European patent application publication No. 0132375) in tetrahydrofuran (10 ml) was added dropwise over five minutes to a stirred, ice-cooled suspension of lithium aluminium hydride (0.19 g) in tetrahydrofuran (20 ml). The ice-cooled mixture was stirred for 40 minutes, quenched into water and partitioned between ethyl acetate and 1M hydrochloric acid. The layers were separated and the organic layer was washed with water, dried over Na2SO4 and evaporated. The residue was purified by chromatography on SiO2 (8g) using dichloromethane plus 0-50% ethyl acetate as the eluant. Appropriate fractions were combined and evaporated and the residue triturated with ether/hexane. The resulting solid was collected, washed with ether and dried to give the title compound (0.25 g), m.p. 86°-89° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([CH2:7][O:8][CH2:9][C@H:10]([CH3:24])[C@H:11]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[C@@H:12]([CH3:15])[CH2:13]O)=[CH:5][CH:4]=1.CCN(CC)CC.[H-].[Na+].[CH3:36][CH2:37][O:38][C:39]([CH3:41])=[O:40].CCCCCC>>[CH2:37]([O:38][C:39](=[O:40])/[CH:41]=[CH:13]/[C@H:12]([CH3:15])[C@@H:11]([O:16][Si:17]([C:20]([CH3:22])([CH3:21])[CH3:23])([CH3:19])[CH3:18])[C@@H:10]([CH3:24])[CH2:9][O:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:26][CH:25]=1)[CH3:36]
Reactant: COc1ccc(COC[C@H](C)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)CO)cc1
Reactant: CCOC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CCCCCC
Product: CCOC(=O)/C=C/[C@H](C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)COCc1ccc(OC)cc1
Yield: 63 %

Procedure:
The procedure for 10 was used with the aldehyde from 21 (17.5 g, 31.6 mmol), Py.SO3 (15.2 g, 95.5 mmol) and Et3N (13.3 mL, 95.5 mmol), NaH (0.90 g, 39.7 mmol) and triethylphosphonoacetate (7.2 mL, 40.3 mmol) to yield 8.96 g (63% for 3 steps) of the ester 22 by flash column chromatography (EtOAc/Hexane 1:9) as a colorless oil: IR (CHCl3) 2957, 2931, 2856, 1720, 1651, 1613, 1513, 1463, 1366, 1250, 1180, 1093, 1077, 837 cm−1; 1H NMR (300 MHz, CDCl3) ε7.31-7.27 (m, 2H), 7.03 (dd, J=15.8, 7.8 Hz, 1H), 6.93-6.91 (m, 2H), 5.83 (dd, J=15.8, 1.3 Hz, 1H), 4.48b -4.40 (m, 2H), 4.23 (q, J=7.1 Hz, 2H), 3.84 (s, 3H), 3.67 (m, 1H), 3.52 (m, 1H), 3.30 (dd, J=9.1, 7.2 Hz, 1H), 2.59 (m, 1H), 2.00 (m, 1H), 1.33 (t, J=7.1 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H), 1.01 (d, J=7.0 Hz, 3H), 0.94 (s, 9H), 0.08 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 166.5, 159.0, 152.7, 130.6, 129.0, 120.4, 113.6, 76.8, 72.5, 71.8, 60.0, 55.1, 40.2, 38.0, 26.0, 18.2, 14.8, 14.3, 14.2, −4.0, −4.2; LRMS (ESI) 473.2 [M+Na]+; HRMS (ESI) calcd for C25H42O5SiNa 473.2699 [M+Na]+, found 473.2716; [α]20D−28.3 (c 0.41, CHCl3).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([S:12](Cl)(=[O:14])=[O:13])=[C:7]([CH3:16])[CH:6]=1)[C:2]#[CH:3].[OH:17][CH2:18][C@:19]([OH:69])([CH3:68])[C:20](=[O:67])[C@@H:21]([NH:26][C:27](=[O:66])[C@@H:28]([NH:36][C:37](=[O:65])[C@@H:38]([NH:43][C:44](=[O:64])[C@@H:45]([NH:54][C:55](=[O:63])[CH2:56][N:57]1[CH2:62][CH2:61][O:60][CH2:59][CH2:58]1)[CH2:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH2:39][CH:40]([CH3:42])[CH3:41])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:22][CH:23]([CH3:25])[CH3:24]>>[CH3:11][C:9]1[CH:10]=[C:5]([O:4][CH2:1][C:2]#[CH:3])[CH:6]=[C:7]([CH3:16])[C:8]=1[S:12]([O:17][CH2:18][C:19]([OH:69])([CH3:68])[C:20](=[O:67])[C@H:21]([CH2:22][CH:23]([CH3:24])[CH3:25])[NH:26][C:27](=[O:66])[C@H:28]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[NH:36][C:37](=[O:65])[C@H:38]([CH2:39][CH:40]([CH3:42])[CH3:41])[NH:43][C:44](=[O:64])[C@H:45]([CH2:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[NH:54][C:55](=[O:63])[CH2:56][N:57]1[CH2:62][CH2:61][O:60][CH2:59][CH2:58]1)(=[O:14])=[O:13]
Reactant: CC(C)C[C@H](NC(=O)[C@H](CCc1ccccc1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)[C@](C)(O)CO
Reactant: C#CCOc1cc(C)c(S(=O)(=O)Cl)c(C)c1
Product: C#CCOc1cc(C)c(S(=O)(=O)OCC(C)(O)C(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCc2ccccc2)NC(=O)CN2CCOCC2)c(C)c1

Procedure:
Prepared in a similar manner to compound 13, except from 4-(propargyloxy)-2,6-dimethylbenzene-1-sulfonyl chloride and (S)—N—((S)-1-(((2R,4S)-1,2-dihydroxy-2,6-dimethyl-3-oxoheptan-4-yl)amino)-1-oxo-3-phenylpropan-2-yl)-4-methyl-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide.
Reaction SMILES: [C:1](S)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]#[N:16])[N:10]=1>O1CCCC1>[C:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([C:1]([CH3:4])([CH3:3])[CH3:2])[N:10]=1)#[N:16]
Reactant: N#Cc1cccc(Cl)n1
Reactant: CC(C)(C)S
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)c1cccc(C#N)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 103.2 %

Procedure:
tert-Butyl mercaptan (0.72 g, 7.9 mmol) was dissolved in tetrahydrofuran (100 ml) and added dropwise to sodium hydride (60% oil, 0.35 g, 8.7 mmol). The reaction mixture was stirred at room temperature for 1 hr. A solution of 2-chloro-6-cyanopyridine (1.00 g, 7.2 mmol) in tetrahydrofuran (10 ml) was added to the mixture, and the mixture was stirred at room temperature for 18 hrs. The reaction mixture was concentrated under reduced pressure, diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine and dried. The solvent was evaporated under reduced pressure to give the titled compound (1.19 g, 86%) as an oil.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([NH:11][C:12]([C:14]2[CH:18]=[C:17]([CH2:19][N:20]([S:22]([C:25]3[C:30]([CH3:31])=[CH:29][C:28]([O:32][CH3:33])=[CH:27][C:26]=3[CH3:34])(=[O:24])=[O:23])[CH3:21])[O:16][CH:15]=2)=[O:13])[CH3:10])=[CH:5][CH:4]=1)=O.[OH:35][CH:36]1[CH2:40][CH2:39][NH:38][CH2:37]1.CC(O)=O.ClCCCl>C(Cl)Cl>[OH:35][CH:36]1[CH2:40][CH2:39][N:38]([CH2:1][C:3]2[CH:4]=[CH:5][C:6]([CH:9]([NH:11][C:12]([C:14]3[CH:18]=[C:17]([CH2:19][N:20]([S:22]([C:25]4[C:30]([CH3:31])=[CH:29][C:28]([O:32][CH3:33])=[CH:27][C:26]=4[CH3:34])(=[O:24])=[O:23])[CH3:21])[O:16][CH:15]=3)=[O:13])[CH3:10])=[CH:7][CH:8]=2)[CH2:37]1
Reactant: OC1CCNC1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)NC(C)c3ccc(C=O)cc3)co2)c(C)c1
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: ClCCCl
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)NC(C)c3ccc(CN4CCC(O)C4)cc3)co2)c(C)c1

Procedure:
The title compound was prepared according to general procedure BF using N-[1-(4-formylphenyl)ethyl]-5-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)furan-3-carboxamide (39 mg, 0.08 mmol), 3-hydroxypyrrolidine (8.7 mg, 0.1 mmol), AcOH (7 mg, 0.12 mmol), STAB (34 mg, 0.16 mmol) and DCE (1 mL). The reaction was diluted with DCM (1 mL) and washed with saturated aqueous NaHCO3 solution (5 mL). The organic phase was dried over Na2SO4 and the solvent removed in vacuo. The crude product was purified by FCC eluting with 2-10% MeOH in DCM to afford the title compound.
Reaction SMILES: C([O:3][C:4](=[O:18])[CH:5]([OH:17])[CH:6]1[C:11](=[O:12])[NH:10][C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=2[S:7]1)C.[OH-].[Na+].O>CCO>[OH:17][CH:5]([CH:6]1[C:11](=[O:12])[NH:10][C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=2[S:7]1)[C:4]([OH:18])=[O:3]
Reactant: CCOC(=O)C(O)C1Sc2ccccc2NC1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)C(O)C1Sc2ccccc2NC1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 76 %

Procedure:
To a solution of hydroxy-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-2-yl)-acetic acid ethyl ester (1.12 mmol) in 5 mL of EtOH is added NaOH (1N) (2.24 mmol) and the mixture is stirred at room temperature for 1 hour. Water (20 ml) is added into the mixture followed by extraction (EtOAc, 3×10 mL). The aqueous layer is then treated with HCl (1N) (2.5 mL) and extracted with EtOAc (3×30 mL). The combined extracts are washed with brine and dried over MgSO4. After filtering off the drying agent, the solution is concentrated to provide the crude product hydroxy-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-2-yl)-acetic acid as a off white solid. Yield: 76%. MS: (ES+): 240 [M+1].
Reaction SMILES: [O:1]=[C:2]([CH3:10])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8].[CH3:11]O>S(=O)(=O)(O)O>[O:1]=[C:2]([CH3:10])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:11])=[O:8]
Reactant: CC(=O)CCCCC(=O)O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)CCCCC(C)=O
Reaction time: 1.5 h

Procedure:
Dissolve 10 g 6-oxoheptanoic acid (69.4 mmol) in 100 ml methanol. Add a few drops of concentrated sulphuric acid and stir for 1.5 h under reflux. Then concentrate by evaporation. Take up in dichloromethane and wash once with satd. sodium hydrogencarbonate solution. Separate the phases, dry the organic phase and concentrate by evaporation. 10.1 g (91.1% of theor.) of the target compound is obtained.
Reaction SMILES: C(=O)([S:3][CH2:4][C:5]1[O:6][C:7]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:8][CH:9]=1)C.C[S-].[Na+]>C(Cl)(Cl)Cl.CO>[N:12]1[CH:13]=[CH:14][CH:15]=[C:10]([C:7]2[O:6][C:5]([CH2:4][SH:3])=[CH:9][CH:8]=2)[CH:11]=1
Reactant: CC(=O)SCc1ccc(-c2cccnc2)o1
Agent: C[S-]
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: SCc1ccc(-c2cccnc2)o1
Yield: 62.7 %

Procedure:
(See FIG. 7.) To a solution of 13 (10 mg, 0.05 mmol) in CHCl3/CH3OH (1.5 mL, 2:1, v:v) was added sodium thiomethoxide (3 mg, 0.05 mmol) and the resultant solution was stirred under argon for 10 min. The solvent was removed with a stream of argon and the residue was applied directly to a TLC plate (20×20 cm, 250 μm silica gel), developed (EtOAc/Hex, 5/95, Rf=0.12), the product band was scraped, extracted with dichloromethane and the solvent was removed in vacuo to afford the title compound 14 (6 mg, 68% yield) as a white film: 1H NMR (CD3OD) δ 8.72 (m, 1H), 8.19 (m, 1H), 7.96 (m, 1H), 7.28 (m, 1H), 6.66 (d, J=3.3 Hz, 1H), 6.07 (d, J=3.3 Hz, 1H), 3.59 (s, 2H), LRMS (ESI) m/z calcd for C10H10NOS [M+H]+ 192. found 192.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[CH:15]=[C:14]([C:16]4[S:17][C:18]5[C:24]([C:25]6[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=6)=[C:23]([C@H:32]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:22]([CH3:43])=[CH:21][C:19]=5[N:20]=4)[CH:13]=[CH:12][N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C([O-])([O-])=O.[Cs+].[Cs+].[C:50]([N:57]1[CH2:60][CH:59](I)[CH2:58]1)([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51]>CN(C=O)C>[C:39]([O:38][C@@H:32]([C:23]1[C:22]([CH3:43])=[CH:21][C:19]2[N:20]=[C:16]([C:14]3[CH:13]=[CH:12][N:11]=[C:10]([C:6]4[CH:5]=[C:4]5[C:9](=[CH:8][CH:7]=4)[N:1]([CH:59]4[CH2:58][N:57]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:60]4)[N:2]=[CH:3]5)[CH:15]=3)[S:17][C:18]=2[C:24]=1[C:25]1[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=1)[C:33]([O:35][CH2:36][CH3:37])=[O:34])([CH3:42])([CH3:41])[CH3:40]
Reactant: CC(C)(C)OC(=O)N1CC(I)C1
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(-c4ccc5[nH]ncc5c4)c3)sc2c1-c1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(-c4ccc5c(cnn5C5CN(C(=O)OC(C)(C)C)C5)c4)c3)sc2c1-c1ccc(Cl)cc1
Temperature: 60 °C

Procedure:
To a solution of (S)-ethyl 2-(2-(2-(1H-indazol-5-yl)pyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (110 mg, 0.18 mmol) in DMF (3 mL) was added Cs2CO3 (117 mg, 0.36 mmol) and 1-Boc-3-iodoazetidine (76 mg, 0.27 mmol). The reaction mixture was heated at 60° C. overnight. The reaction mixture was washed by saturated NaHCO3, extracted by EtOAc, the organic phase was dried over MgSO4, filtered, concentrated down, purified by silica gel column, eluting by 0-60% EtOAc in hexanes to give the product. LCMS-ESI+: calc'd for C42H44ClN5O5S: 766.3 (M+H+); found: 766.3.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])=[CH:18][CH:17]=3)[CH2:12][CH2:11]2)[CH:5]=1)([O-])=O.[H][H]>CO.[Pd]>[NH2:1][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:11][CH2:12][N:13]([C:16]3[CH:17]=[CH:18][C:19]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])=[CH:20][CH:21]=3)[CH2:14][CH2:15]2)[CH:5]=1
Reactant: CS(=O)(=O)Nc1ccc(N2CCN(c3cc([N+](=O)[O-])ccn3)CC2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CS(=O)(=O)Nc1ccc(N2CCN(c3cc(N)ccn3)CC2)cc1
Yield: 59.7 %

Procedure:
A solution of N-{4-[4-(4-nitropyrid-2-yl)piperazin-1-yl]phenyl}methanesulphonamide (100 mg) in methanol (40 ml) was hydrogenated at 3 bar and 22° C. in the presence of 5% palladium on carbon (20 mg) until no more hydrogen was taken up. The catalyst was filtered off and the filtrate was evaporated. The residue was crystallised from aqueous methanol to give the title compound (55 mg), m.p. 225°-227° C. Found: C,55.50; H,6.04; N,19.66. C16H21N5O2S requires: C,55.31; H,6.09; N,20.16%.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[C:5]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[C:11]([OH:19])[CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[CH:21]1([C:24]2[C:29]([CH2:30][CH2:31]O)=[CH:28][N:27]=[C:26]([C:33]3[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=3)[N:25]=2)[CH2:23][CH2:22]1>>[CH2:1]([O:3][C:4](=[O:20])[C:5]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[C:11]([O:19][CH2:31][CH2:30][C:29]2[C:24]([CH:21]3[CH2:23][CH2:22]3)=[N:25][C:26]([C:33]3[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:40])[F:41])=[CH:35][CH:34]=3)=[N:27][CH:28]=2)[CH:10]=1)([CH3:7])[CH3:6])[CH3:2]
Reactant: CCOC(=O)C(C)(C)Oc1cc(O)cc2ccccc12
Reactant: OCCc1cnc(-c2ccc(C(F)(F)F)cc2)nc1C1CC1
Product: CCOC(=O)C(C)(C)Oc1cc(OCCc2cnc(-c3ccc(C(F)(F)F)cc3)nc2C2CC2)cc2ccccc12

Procedure:
A] In analogy to the procedures described in example 4D] and 4E], 2-(3-hydroxy-naphthalen-1-yloxy)-2-methyl-propionic acid ethyl ester (example 14C]) was reacted with 2-[4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-ethanol (example 16B]) to give 2-(3-{2-[4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-ethoxy}-naphthalen-1-yloxy)-2-methyl-propionic acid ethyl ester, which was subsequently saponified to yield the title compound as light yellow solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:11]([F:16])([F:15])([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=[O:6].[CH3:17][C:18]([CH3:20])=[O:19].Cl>C1COCC1>[OH:19][C:18]([C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:11]([F:16])([F:15])([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=[O:6])([CH3:20])[CH3:17]
Reactant: O=C(O)c1cc(Br)cc(S(F)(F)(F)(F)F)c1
Reactant: CC(C)=O
Agent: Cl
Solvent: C1CCOC1
Product: CC(C)(O)c1cc(C(=O)O)cc(S(F)(F)(F)(F)F)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Under argon, 7.6 g (23.3 mmol) of the compound of Example 15A were dissolved in 76 ml of THF, and a few granules of 4 Å molecular sieve were added. The mixture was then cooled to 0° C., and 53.7 ml (69.8 mmol) of a 1.3 M solution of 2-propylmagnesium chloride/lithium chloride complex in THF were slowly added dropwise. After the addition had ended, the reaction mixture was stirred at 0° C. for another 30 min. 2.6 ml (34.9 mmol) of anhydrous acetone were then added, and the reaction was stirred at 0° C. for another 1 h. 90 ml of 1 M hydrochloric acid were then added, and the reaction was allowed to slowly warm to RT over a period of 40 min. The mixture was then extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The residue was triturated with petroleum ether with a little diethyl ether added, filtered off and dried. This gave 5.8 g (80% of theory) of the title compound as a white solid.
Reaction SMILES: [K].[C:2]([C:4]([CH3:17])([C:6](=[O:16])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[CH3:5])#[N:3].Cl[C:19]1[CH:28]=[N:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:25]=2)[N:20]=1.O>CN(C)C=O>[C:2]([C:4]([CH3:17])([C:6](=[O:16])[CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][C:19]2[CH:28]=[N:27][C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:29]([F:30])([F:31])[F:32])[CH:25]=3)[N:20]=2)=[CH:13][CH:14]=1)[CH3:5])#[N:3]
Reactant: CC(C)(C#N)C(=O)COc1ccc(O)cc1
Reactant: FC(F)(F)c1ccc2nc(Cl)cnc2c1
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C#N)C(=O)COc1ccc(Oc2cnc3cc(C(F)(F)F)ccc3n2)cc1
Temperature: 100 °C
Yield: 47.1 %

Procedure:
2.20 Grams of a potassium salt of 2-cyano-2-methyl-4-(4-hydroxyphenoxy)-3-butanone and 1.69 g of 2-chloro-6-trifluoromethylquinoxaline were refluxed in 50 nl of N,N-dimethylformamide under heat at 100° C. for 4 hours. The reaction mixture was added to water, and after the mixture was subjected to extraction with chloroform, the extract was concentrated. The residue was separated and purified by column chromatography to give 1.67 g of a compound No. 166 which was a light yellow solid (melting point 113°-115° C.). The yield was 47.1%. The compound No. 166 was analyzed, and the results are shown in Tables 1 to 23.