Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:76])/[CH:4]=[CH:5]\[CH:6]=[CH:7]\[C@@H:8]([CH3:75])[C@@H:9]([O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:70])[CH3:69])[CH2:10][C@H:11]([O:59][Si:60]([C:63]([CH3:66])([CH3:65])[CH3:64])([CH3:62])[CH3:61])/[CH:12]=[CH:13]\[C@H:14]([CH3:58])[C@H:15]([O:50][Si:51]([C:54]([CH3:57])([CH3:56])[CH3:55])([CH3:53])[CH3:52])[C@@H:16]([CH3:49])[CH2:17][CH2:18][CH2:19][CH2:20][C@@H:21]([O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[C@H:22]([CH3:40])[C@@H:23]([O:30]CC1C=CC(OC)=CC=1)[C@@H:24]([CH3:29])/[CH:25]=[CH:26]\[CH:27]=[CH2:28].C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>CCOC(C)=O.CCCCCC>[CH3:1][O:2][C:3](=[O:76])/[CH:4]=[CH:5]\[CH:6]=[CH:7]\[C@@H:8]([CH3:75])[C@@H:9]([O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:69])[CH3:70])[CH2:10][C@H:11]([O:59][Si:60]([C:63]([CH3:66])([CH3:65])[CH3:64])([CH3:61])[CH3:62])/[CH:12]=[CH:13]\[C@H:14]([CH3:58])[C@H:15]([O:50][Si:51]([C:54]([CH3:55])([CH3:56])[CH3:57])([CH3:53])[CH3:52])[C@@H:16]([CH3:49])[CH2:17][CH2:18][CH2:19][CH2:20][C@@H:21]([O:41][Si:42]([C:45]([CH3:46])([CH3:47])[CH3:48])([CH3:43])[CH3:44])[C@H:22]([CH3:40])[C@@H:23]([OH:30])[C@@H:24]([CH3:29])/[CH:25]=[CH:26]\[CH:27]=[CH2:28]
Reactant: C=C/C=C\[C@H](C)[C@H](OCc1ccc(OC)cc1)[C@@H](C)[C@@H](CCCC[C@H](C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)/C=C\[C@H](C[C@H](O[Si](C)(C)C(C)(C)C)[C@H](C)/C=C/C=C\C(=O)OC)O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: C=C/C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](CCCC[C@H](C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)/C=C\[C@H](C[C@H](O[Si](C)(C)C(C)(C)C)[C@H](C)/C=C/C=C\C(=O)OC)O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Yield: 81714.7 %

Procedure:
The procedure for 47 was used with 76 (0.38 g, 0.34 μmol) and DDQ (0.084 g, 0.37 mmol) to yield 77 (0.28 g, 82%) after flash column chromatography (EtOAc/hexane 1:9) as a colorless oil: IR (CHCl3) 3542, 2956, 2856, 1722, 1640, 1462, 1254, 1175, 1086, 1004, 836, 773 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.39 (dd, J=15.2, 11.2 Hz, 1H), 6.63 (ddd, J=16.9, 10.5, 10.4 Hz, 1H), 6.53 (t, J=11.3 Hz, 1H), 6.09 (t, J=1.0 Hz, 1H), 5.98 (dd, J=8.3, 7.1 Hz, 1H), 5.58 (d, J=11.3 Hz, 1H), 5.45-5.39 (m, 2H), 5.26 (dd, J=10.8, 8.4 Hz, 1H), 5.20 (d, J=16.9 Hz, 1H), 5.11(d, J=10.1 Hz, 1H), 4.53 (m, 1H), 3.95 (m, 1H), 3.76 (m, 1H), 3.71 (s, 3H), 3.47 (m, 1H), 3.40 (m, 1H), 2.82 (m, 1H), 2.55 (m, 1H), 2.20 (br, 1H), 1.72 (m, 2H), 1.60-1.35 (m, 5H), 1.32-1.10 (m, 5H), 1.04 (d, J=6.8 Hz, 3H), 0.99-0.83 (m, 48H), 0.12-0.03 (m, 24H); 13C NMR (75 MHz, CDCl3) δ 166.7, 147.1, 145.4, 135.2, 132.6, 132.5, 132.3, 130.0, 126.8, 117.7, 115.5, 80.2, 77.3, 76.2, 72.1, 66.5, 50.9, 43.4, 42.5, 38.3, 38.1, 36.1, 35.8, 34.7, 33.7, 28.3, 26.2, 25.94, 25.89, 25.5, 19.5, 18.4, 18.1, 17.7, 14.9, 13.3, 7.2, −3.0, −3.6, −3.8, −4.18, −4.20, −4.37, −4.41; LRMS (ESI) 1029.7 [M+Na]+, 875.6, 379.3; HRMS (ESI) calcd for C56H110O7Si4Na 1029.7226 [M+Na]+, found 1029.7244; [α]20D−18.7 (c 0.62, CHCl3).
Reaction SMILES: C1C=CC=CC=1.[CH2:7]([C:9]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][CH3:21])[C:10]=1/[N:11]=[CH:12]/[CH:13]([CH3:15])[CH3:14])[CH3:8].C([N-]C(C)C)(C)C.[Li+:29]>CCCCC>[CH2:7]([C:9]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][CH3:21])[C:10]=1[N-:11][CH:12]=[C:13]([CH3:15])[CH3:14])[CH3:8].[Li+:29]
Reactant: CCc1cccc(CC)c1/N=C/C(C)C
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CCCCC
Solvent: c1ccccc1
Product: CCc1cccc(CC)c1[N-]C=C(C)C
Temperature: 50 °C
Yield: 80.6 %

Procedure:
Benzene (70 mL) and compound A (6.63 g, 32.6 mmol) were combined. Solid lithium diisopropylamide (4.01 g, 37.4 mmol) was then added. The mixture was heated to 50° C. to form a cloudy red-orange solution. After a few hours the solution was filtered through diatomaceous earth to afford a clear yellow solution. The volatiles were evaporated to give a yellow solid. Pentane (15 mL) was added and the mixture was stirred briefly and then cooled to −10° C. overnight. The product was then collected on a glass frit and washed with pentane (2×20 mL) to yield 5.50 g of compound B (80.6%) as a white solid that was dried under reduced pressure and used without further characterization.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](I)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(#N)C.[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:24]#[C:23][Si:20]([CH3:22])([CH3:21])[CH3:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#C[Si](C)(C)C
Reactant: Ic1ccc(OCc2ccccc2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1ccc(OCc2ccccc2)cc1
Temperature: 60 °C
Reaction time: 17 h

Procedure:
A resealable tube was charged with 1-benzyloxy-4-iodobenzene 100 (5.00 g, 16.1 mmol), acetonitrile (80 mL), and triethylamine (10 mL). Dichlorobis(triphenylphosphine)palladium (II) (0.733 g, 1.05 mmol), copper (I) iodide (0.200 g, 1.05 mmol), and (trimethylsilyl)acetylene (2.06 g, 2.96 mL, 20.9 mmol) were added. The system was purged with argon, the tube was sealed, and the mixture stirred at 60° C. for 17 h. The reaction mixture was filtered twice through a pad of Celite along with ethyl acetate. The filtrate was concentrated to afford (4-benzyloxy-phenylethynyl)trimethylsilane (101) as an orange brown solid which was used without purification.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[C:8]#[N:9])=O.[NH2:13][C:14]([NH2:16])=[S:15]>CO>[NH2:16][C:14]1[S:15][CH:2]=[C:3]([C:5]2[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=2)[C:8]#[N:9])[N:13]=1
Reactant: NC(N)=S
Reactant: N#Cc1cccc(C(=O)CBr)c1
Solvent: CO
Product: N#Cc1cccc(-c2csc(N)n2)c1
Temperature: 0 °C

Procedure:
16.9 g of 3-bromoacetyl-benzonitrile were placed in 50 ml of methanol and treated at room temperature with 8 g of thiourea. The mixture was boiled for 21/2 hours and then cooled to 0° C. while stirring slowly. The product separated as the salt, was filtered off and converted into the base by the addition of 100 ml of 2N sodium hydroxide solution. The aqueous suspension was extracted with a total of 700 ml of methylene chloride and the organic phase was dried with magnesium sulphate. 9.6 g of 3-(2-amino-thiazol-4-yl)-benzonitrile separated upon concentration.
Reaction SMILES: C1(O[C:8](=[O:27])[NH:9][C:10]2[S:11][C:12]3[C:18]([CH:19]4[CH2:24][O:23][CH2:22][CH2:21][O:20]4)=[CH:17][CH:16]=[C:15]([O:25][CH3:26])[C:13]=3[N:14]=2)C=CC=CC=1.[CH3:28][C:29]1([OH:35])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.N1C=CC=CC=1>C(Cl)(Cl)Cl>[O:20]1[CH2:21][CH2:22][O:23][CH2:24][CH:19]1[C:18]1[C:12]2[S:11][C:10]([NH:9][C:8]([N:32]3[CH2:33][CH2:34][C:29]([OH:35])([CH3:28])[CH2:30][CH2:31]3)=[O:27])=[N:14][C:13]=2[C:15]([O:25][CH3:26])=[CH:16][CH:17]=1
Reactant: COc1ccc(C2COCCO2)c2sc(NC(=O)Oc3ccccc3)nc12
Reactant: CC1(O)CCNCC1
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: COc1ccc(C2COCCO2)c2sc(NC(=O)N3CCC(C)(O)CC3)nc12

Procedure:
From (+)-(7-[1,4]dioxan-2yl-4-methoxy-benzothiazol-2-yl)-carbamic acid phenyl ester with 4-methyl-piperidin-4-ol and pyridine in chloroform. [α]D20=+25.2° (c=1.07, CHCl3), ES-MS m/e (%): 408 (M+H+, 100).
Reaction SMILES: [F:1][C:2]([F:31])([F:30])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)([OH:18])[CH:11]([N:13]2[N:17]=[N:16][CH:15]=[N:14]2)[CH3:12])=[CH:6][CH:5]=1.[H-].[Na+].[CH3:34]I>CN(C)C=O.O>[F:29][C:26]([F:27])([F:28])[O:25][C:22]1[CH:23]=[CH:24][C:19]([C:10]([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:30])[F:31])=[CH:5][CH:6]=2)([O:18][CH3:34])[CH:11]([N:13]2[N:17]=[N:16][CH:15]=[N:14]2)[CH3:12])=[CH:20][CH:21]=1
Reactant: CC(n1ncnn1)C(O)(c1ccc(OC(F)(F)F)cc1)c1ccc(OC(F)(F)F)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(c1ccc(OC(F)(F)F)cc1)(c1ccc(OC(F)(F)F)cc1)C(C)n1ncnn1
Reaction time: 20 h

Procedure:
1,1-bis(4-trifluoromethoxyphenyl)-2-(2H-tetrazol-2-yl)propanol (220 g) was added to a stirred suspension of sodium hydride (24 mg of a 50% dispension in oil) in dry dimethylformamide (6.0 cm3) at the ambient temperature under a nitrogen atmosphere, and the mixture stirred for a further 2 hours after which methyl iodide (71 mg) was added and the resultant mixtures stirred for a further 20 hours. After diluting with water the mixture was extracted with diethyl ether (3×15 cm3), the extracts were combined, dried over anhydrous magnesium sulphate and concentrated by evaporation of the solvent under reduced pressure. The residual yellow oil was subjected to h.p.l.c using a silica gel column eluted with a mixture of n-hexane and ethyl acetate (5:1 by volume) to yield 1,1-bis(4-trifluoromethoxyphenyl)-1-methoxy-2-(2H-tetrazol-2-yl)propane.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[OH-].[K+].CS(C)=O.Br[C:18]([CH3:25])([CH3:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20]>O>[CH2:22]([O:21][C:19](=[O:20])[C:18]([O:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2)([CH3:25])[CH3:24])[CH3:23]
Reactant: Oc1cccc2[nH]ccc12
Reactant: CCOC(=O)C(C)(C)Br
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CCOC(=O)C(C)(C)Oc1cccc2[nH]ccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 77.6 %

Procedure:
A mixture of 4-hydroxyindole (0.100 g, 0.75 mmol, 1.0 eq), powdered potassium hydroxide (0.046 g, 0.83 mmol, 1.1 eq), and DMSO (2 mL) was stirred at room temperature for 1 hour and then ethyl 2-bromo-2-methylpropionate (0.161 g, 0.12 mL, 0.83 mmol, 1.1 eq) was added to the above mixture dropwise. The reaction mixture was stirred at room temperature for another 2 hours before 15 mL of water was added. The mixture was extracted with ethyl acetate (2×30 mL). The organic layer was collected, combined, washed with water (6×25 mL) and brine (2×20 mL), and dried over anhydrous Na2SO4. The solvent was removed in vacuo. The residue thus obtained was purified by flash chromatograph over silica gel using hexane/ethyl acetate (95/5) as an eluant to afford 2-(1H-indol-4-yloxy)-2-methylpropionic acid ethyl ester (0.144 g, yield: 80%).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[CH2:13](Br)[CH:14]=[CH2:15]>>[CH2:15]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11])[CH:14]=[CH2:13]
Reactant: O=Cc1ccc(O)c([N+](=O)[O-])c1
Reactant: C=CCBr
Product: C=CCOc1ccc(C=O)cc1[N+](=O)[O-]

Procedure:
Analogously to Method F, 25 g of 4-hydroxy-3-nitrobenzaldehyde and 25.1 ml of allyl bromide are reacted. The title compound is obtained as a slightly yellowish solid. Rf=0.30 (1:2 EtOAc-heptane). Rt=4.00.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]([C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH2:23])[C:18]([NH2:21])=[N:19][CH:20]=2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si:30]([O:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44][C:45](Cl)=[O:46])=[CH:40][CH:39]=1)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31].O>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[Si:30]([O:37][C:38]1[CH:39]=[CH:40][C:41]([CH2:44][C:45]([NH:21][C:18]2[C:17]([C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH2:23])=[N:16][C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3])=[CH:14][CH:13]=3)=[CH:20][N:19]=2)=[O:46])=[CH:42][CH:43]=1)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(CC(=O)Cl)cc1
Reactant: C=C(c1ccccc1)c1nc(-c2ccc(O[Si](C)(C)C(C)(C)C)cc2)cnc1N
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: O
Product: C=C(c1ccccc1)c1nc(-c2ccc(O[Si](C)(C)C(C)(C)C)cc2)cnc1NC(=O)Cc1ccc(O[Si](C)(C)C(C)(C)C)cc1
Temperature: 50 °C
Reaction time: 16 h
Yield: 33.3 %

Procedure:
Under an argon atmosphere, to a mixture of 5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(1-phenylvinyl)pyrazin-2-amine (7c) (543 mg, 1.35 mmol) and 4-(dimethylamino)pyridine (15.0 mg, 123 μmol) dissolved in anhydrous pyridine (20 mL) was added 2-[4-(tert-butyldimethylsilyloxy)phenyl]acetyl chloride (10) prepared above at 0° C., and the mixture was heated with stirring at 50° C. for 16 hours. After cooling to room temperature, to this was added water and the product was extracted with ethyl acetate (200 mL×3). The combined organic extract was washed successively with water (200 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=3/1) to give Compound 11c (292 mg, 448 μmol, 33.3%) as a yellow foamy solid. Rf=0.26 (n-hexane/diethyl ether=2/3); 1H NMR (400 MHz, DMSO-d6) δ 0.13 (s, 6H), 0.18 (s, 6H), 0.91 (s, 9H), 0.92 (s, 9H), 3.22 (s, 2H), 5.51 (s, 1H), 5.65 (s, 1H), 6.67-6.74 (AA′BB′, 2H), 6.90-6.97 (AA′BB′, 2H), 6.97-7.03 (AA′BB′, 2H), 7.19-7.26 (m, 2H), 7.26-7.31 (m, 3H), 7.91-7.98 (AA′BB′, 2H), 8.95 (s, 1H), 10.19 (s, 1H); 13C NMR (75.5 MHz, acetone-d6) δ −4.3 (4C), 18.6, 18.7, 26.0 (6C), 42.5, 118.8, 120.5 (2C), 121.1 (2C), 127.9 (2C), 128.4, 128.6, 128.78 (2C), 128.84 (2C), 130.1, 131,3 (2C), 138.4, 140.0, 144.2, 146.9, 148.7, 148.9, 155.1, 157.9, 169.7; IR (KBr, cm−1) 546, 696, 781, 806, 839, 914, 1007, 1082, 1169, 1261, 1362, 1420, 1435, 1472, 1508, 1605, 1670, 2857, 2886, 2930, 2955, 3030, 3055, 3231; HRMS (ESI+) m/z 652.3390 ([M+H]+, C38H50N3O3Si2+ requires 652.3385).
Reaction SMILES: [Cl:1][C:2]1[S:3][C:4]([CH2:15][C:16]([O:18][CH3:19])=[O:17])=[C:5](/[CH:7]=[CH:8]/[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:6]=1.CO[CH:22](OC)[N:23]([CH3:25])[CH3:24]>>[Cl:1][C:2]1[S:3][C:4]([C:15](=[CH:22][N:23]([CH3:25])[CH3:24])[C:16]([O:18][CH3:19])=[O:17])=[C:5](/[CH:7]=[CH:8]/[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:6]=1
Reactant: COC(=O)Cc1sc(Cl)nc1/C=C/c1ccccc1
Reactant: COC(OC)N(C)C
Product: COC(=O)C(=CN(C)C)c1sc(Cl)nc1/C=C/c1ccccc1
Temperature: 50 °C

Procedure:
A mixture of 5.9 g of the product of Step B and 55 ml of dimethylformamide dimethyl acetal was heated to 50° C. and after 4 hours at this temperature, the mixture was allowed to return to 25° C. The reaction mixture was evaporated to dryness and the residue was chromatographed on silica, eluting with a hexane-ethyl acetate mixture (7-3) to obtain 3.3 g of the desired product. Thin layer chromatography; Rf=0.18 [eluant: hexane-ethyl acetate (7-3)].
Reaction SMILES: [CH:1]1([CH3:13])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([C:10](Cl)=[O:11])[CH2:2]1.[NH2:14][C:15]([CH3:19])([CH3:18])[CH2:16][OH:17]>>[CH3:18][C:15]([NH:14][C:10]([CH:3]1[CH:4]([CH:7]([CH3:9])[CH3:8])[CH2:5][CH2:6][CH:1]([CH3:13])[CH2:2]1)=[O:11])([CH3:19])[CH2:16][OH:17]
Reactant: CC1CCC(C(C)C)C(C(=O)Cl)C1
Reactant: CC(C)(N)CO
Product: CC1CCC(C(C)C)C(C(=O)NC(C)(C)CO)C1

Procedure:
p-Menth-3-oyl chloride (3.0 g.) was reacted with 2-amino-2-methyl-propan-1-ol (3.0 g.) according to the procedure of Example 3. Product N-(1,1-dimethyl-2-hydroxyethyl)-p-menthane-3-carboxamide was obtained as a crystalline solid which was recrystallised from aqueous methanol. M.p. 123°.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:15][N:14]([CH2:16][C:17]2[S:18][CH:19]=[CH:20][N:21]=2)[C:13](=[O:22])[C@H:12]([N:23](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[CH2:11][CH2:10]1.FC(F)(F)C(O)=O>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[NH2:23][C@@H:12]1[CH2:11][CH2:10][C@@H:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[F:1])[CH2:15][N:14]([CH2:16][C:17]2[S:18][CH:19]=[CH:20][N:21]=2)[C:13]1=[O:22]
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)[C@@H]1CC[C@@H](c2cccc(F)c2F)CN(Cc2nccs2)C1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N[C@@H]1CC[C@@H](c2cccc(F)c2F)CN(Cc2nccs2)C1=O
Yield: 0.1 %

Procedure:
A solution of di-tert-butyl [(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(1,3-thiazol-2-ylmethyl)azepan-3-yl]imidodicarbonate (0.481 g, 0.895 mmol) in DCM (10 mL) was treated with trifluoroacetic acid (3 mL). After lh the reaction was diluted with saturated aqueous sodium bicarbonate, the layers separated, and the aqueous phase extracted with DCM (2×). The organic washes were combined, dried over magnesium sulfate, and concentrated to afford the title compound (0.30 mg). MS 338.2 (M+1).
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:9]1[CH:10]=[C:11]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:13][CH:14]=1.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CN(C=O)C>[C:1]1([S:7][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=[N+]([O-])c1cccc(I)c1
Reactant: Sc1ccccc1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cccc(Sc2ccccc2)c1
Temperature: 100 °C

Procedure:
A mixture of thiophenol (1.0 g, 9.1 mmol), 3-iodonitrobenzene (1.9 g, 7.6 mmol), CuI (0.14 g, 0.76 mmol), K2CO3 (1.67 g, 12.1 mmol), and DMF (10 mL) was heated to 100° C. in a flame-dried sealed tube for 16 h. The mixture was allowed to cool and was poured over ice. The resulting mixture was extracted with EtOAc (2×), and the organic extracts were combined and washed sequentially with equal volumes of aqueous 1M HCl, water, and aqueous 1M NaOH. The solution was dried, concentrated, and the residue was purified by FCC (100:0 to 95:5 hexanes/EtOAc) to provide the titled compound, which was contaminated with ca. 10% thiophenol (1.43 g), and was taken on to subsequent steps without further purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14](O)=[O:15])(=[O:11])=[O:10])=[C:4]([C:21]([F:24])([F:23])[F:22])[CH:3]=1.Cl.[CH2:26]([O:28][C:29](=[O:35])[C@H:30]([C@@H:32]([CH3:34])[OH:33])[NH2:31])[CH3:27].O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1>>[CH2:26]([O:28][C:29](=[O:35])[CH:30]([NH:31][C:14](=[O:15])[C:13]1[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=1[S:9](=[O:11])(=[O:10])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[C:21]([F:22])([F:23])[F:24])[CH:32]([OH:33])[CH3:34])[CH3:27]
Reactant: O=C(O)c1ccccc1S(=O)(=O)Nc1ccc(F)cc1C(F)(F)F
Reactant: CCOC(=O)[C@@H](N)[C@@H](C)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC(=O)C(NC(=O)c1ccccc1S(=O)(=O)Nc1ccc(F)cc1C(F)(F)F)C(C)O

Procedure:
Under the conditions of Example 2(a), 3.633 g (10 mmol) of 2-[N-(4-Fluoro-2-trifluoromethylphenyl)sulfamoyl]benzoic acid, 1.736 g (10 mmol) of L-threonine ethyl ester hydrochloride, 1.531 g (10 mmol) of hydroxybenzotriazole, hydrate, as well as 1.012 g (10 mmol) of triethylamine and 2.063 g (10 mmol) of dicyclohexylcarbodiimide are reacted and worked up analogously. The crude product is chromatographed on silica gel. The title compound is eluted with ethyl acetate.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])[C:5]2=[CH:14]OC.CN(C)C=O.[CH2:22]([N:24]([CH2:30][CH3:31])[CH2:25][CH2:26][CH2:27][CH2:28][NH2:29])[CH3:23]>CCOCC>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:29][CH2:28][CH2:27][CH2:26][CH2:25][N:24]([CH2:30][CH3:31])[CH2:22][CH3:23]
Reactant: CCN(CC)CCCCN
Reactant: COC=C1C(=O)NC(=O)c2ccc(Br)cc21
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CCN(CC)CCCCN/C=C1\C(=O)NC(=O)c2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 26 %

Procedure:
A mixture of 6-bromo-4-(methoxymethylene)-isoquinoline-1,3(2H,4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and N1,N1-diethylbutane-1,4-diamine (36.1 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light brown solid, 26.0 mg, (26% yield) MS (ES+): 394.2, (M+H).
Reaction SMILES: Br[CH2:2][C:3]1[S:7][CH:6]=[N:5][C:4]=1[CH2:8][CH3:9].[CH3:10][C:11]1[N:16]=[C:15]([SH:17])[N:14]=[C:13]([OH:18])[CH:12]=1.C(N(CC)CC)C>C(O)C>[CH2:8]([C:4]1[N:5]=[CH:6][S:7][C:3]=1[CH2:2][S:17][C:15]1[N:14]=[C:13]([OH:18])[CH:12]=[C:11]([CH3:10])[N:16]=1)[CH3:9]
Reactant: CCc1ncsc1CBr
Reactant: Cc1cc(O)nc(S)n1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCc1ncsc1CSc1nc(C)cc(O)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 10.1 %

Procedure:
A mixture of 5-(bromomethyl)-4-ethyl-1,3-thiazole (7.0 mmol), 6-methyl-2-sulfanylpyrimidin-4-ol (700 mg, 4.9 mmol), and triethylamine (3.0 mL, 21.5 mmol) in absolute ethanol (70 mL) was stirred at room temperature overnight. The mixture was evaporated, and the residue was treated with 50% diethyl ether/acetone (100 mL). The solid material was removed by filtration. The filtrate was recovered and evaporated. The crude product was purified by flash chromatography (0-10% MeOH/CH2Cl2). The column was repeated 4 times, affording the title compound (132 mg, 10% yield); 1H NMR (500 MHz, DMSO-d6): δ 1.19 (t, 2H, J=7.5 Hz), 2.801 (m, 2H, J=7.5 Hz), 4.55 (s, 2H), 6.05 (s, 1H), 8.85 (s, 1H); M+268.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][N:6]=1)=[O:4].Cl[C:15]1[N:20]=[N:19][C:18]([N:21]2[CH2:26][CH2:25][CH:24]([N:27]3[C:35]4[C:30](=[CH:31][CH:32]=[C:33]([F:36])[CH:34]=4)[CH2:29][CH2:28]3)[CH2:23][CH2:22]2)=[CH:17][CH:16]=1>>[F:36][C:33]1[CH:34]=[C:35]2[C:30]([CH2:29][CH2:28][N:27]2[CH:24]2[CH2:25][CH2:26][N:21]([C:18]3[N:19]=[N:20][C:15]([C:8]4[CH:9]=[CH:10][C:5]([C:3]([NH:2][CH3:1])=[O:4])=[N:6][CH:7]=4)=[CH:16][CH:17]=3)[CH2:22][CH2:23]2)=[CH:31][CH:32]=1
Reactant: Fc1ccc2c(c1)N(C1CCN(c3ccc(Cl)nn3)CC1)CC2
Reactant: CNC(=O)c1ccc(B(O)O)cn1
Product: CNC(=O)c1ccc(-c2ccc(N3CCC(N4CCc5ccc(F)cc54)CC3)nn2)cn1

Procedure:
The title compound was prepared following the procedure as described in Example 1, Method A, STEP 4, reacting 2-(N-methylaminocarbonyl)pyridine-5-boronic acid and 1-(1-(6-chloropyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline.
Reaction SMILES: [F:1][CH:2]([F:33])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[N:20][C:21]([CH:24]([NH:29][CH3:30])[C:25]([F:28])([F:27])[F:26])=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[O:7]C1(C)C)=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[F:33][CH:2]([F:1])[C:3]([NH:5][C@H:9]([CH2:10][F:11])[C@H:8]([OH:7])[C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:19]=[N:20][C:21]([CH:24]([NH:29][CH3:30])[C:25]([F:28])([F:26])[F:27])=[CH:22][CH:23]=2)=[CH:16][CH:17]=1)=[O:4]
Reactant: CNC(c1ccc(-c2ccc([C@H]3OC(C)(C)N(C(=O)C(F)F)[C@@H]3CF)cc2)cn1)C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CNC(c1ccc(-c2ccc([C@@H](O)[C@@H](CF)NC(=O)C(F)F)cc2)cn1)C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h
Yield: 27.4 %

Procedure:
To a solution of 2,2-Difluoro-1-((4S,5R)-4-fluoromethyl-2,2-dimethyl-5-{4-[6-(2,2,2-trifluoro-1-methylamino-ethyl)-pyridin-3-yl]-phenyl}-oxazolidin-3-yl) ethanone (0.12 g, 0.235 mmol) in CH2Cl2 (2 mL) is added trifluoroacetic acid (0.5 mL) at 0° C. then is stirred to room temperature for 2 hours. Reaction solvent evaporated in vacuo then diluted with sodium bicarbonate solution and extract with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by combiflash eluting in 5% Methanol in CH2Cl2 to afford the title compound (0.028 g). 1H-NMR (400 MHz, DMSO) δ: 2.25 (d, J=5.84 Hz, 3H), 3.00-3.04 (m, 1H), 4.31-4.35 (m, 1.5H), 4.41-4.46 (m, 1.5H), 4.55-4.56 (m, 0.5H), 4.65-4.68 (m, 0.5H), 4.90 (m, 1H), 5.93 (d, J=4.36 Hz, 1H), 6.19 (d, J=53.72 Hz, 1H), 7.46 (d, J=8.32 Hz, 2H), 7.95-7.98 (dd, J1=1.96 HzHz, J2=8.32 Hz, 1H), 8.03 (d, J=8.32 Hz, 1H), 8.06 (d, J=8.48 Hz, 2H), 8.71 (d, J=1.88 Hz, 1H), 8.84 (d, J=8.72 Hz, 1H). LC-MS (m/z): [M+H]=436.0.