Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[Si:2](Cl)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[S:16]([C:32]1[CH:37]=[C:36]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:35]=[C:34]([C:42]([CH3:45])([CH3:44])[CH3:43])[C:33]=1[OH:46])[C:17]1[CH:22]=[C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[C:19]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:18]=1[OH:31].C(N(CC)CC)C>C1(C)C=CC=CC=1>[C:38]([C:36]1[CH:35]=[C:34]([C:42]([CH3:45])([CH3:44])[CH3:43])[C:33]2[O:46][Si:2]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[O:31][C:18]3[C:19]([C:27]([CH3:29])([CH3:28])[CH3:30])=[CH:20][C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:22][C:17]=3[S:16][C:32]=2[CH:37]=1)([CH3:41])([CH3:40])[CH3:39]
Reactant: Cl[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)c1cc(Sc2cc(C(C)(C)C)cc(C(C)(C)C)c2O)c(O)c(C(C)(C)C)c1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(C)(C)c1cc2c(c(C(C)(C)C)c1)O[Si](c1ccccc1)(c1ccccc1)Oc1c(cc(C(C)(C)C)cc1C(C)(C)C)S2
Temperature: 92 °C
Yield: 43.3 %

Procedure:
A solution of 12.66 grams of dichlorodiphenylsilane in 50 ml of toluene at 5°-10° C. is added dropwise to a solution of 22.14 grams of 2,2'-thiobis(4,6-di-tert-butylphenol) and 10.12 grams of triethylamine in 100 ml of toluene. The reaction mixture is heated at 92° C. until the reaction is complete as evidenced by the disappearance of the phenolic absorption in the IR spectrum. The triethylamine hydrochloride is removed by filtration and the solvent is removed in vacuo. The residue is recrystallized from 2-butanone to give 13.49 grams (43%) of a white solid: mp 202°-205° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:17][C:16]2[N:12]([C:13]([CH:18]3[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]3)=[N:14][N:15]=2)[C:11]2[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:30]1([Mg]Cl)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:17][C:16]2[N:12]([C:13]([CH:18]3[CH2:19][CH2:20][C:21]([OH:24])([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH2:22][CH2:23]3)=[N:14][N:15]=2)[C:11]2[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cl[Mg]c1ccccc1
Reactant: CC(C)(C)OC(=O)N1Cc2cc(Cl)ccc2-n2c(nnc2C2CCC(=O)CC2)C1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1Cc2cc(Cl)ccc2-n2c(nnc2C2CCC(O)(c3ccccc3)CC2)C1
Reaction time: 2 h
Yield: 42 %

Procedure:
To a solution of 8-chloro-1-(4-oxo-cyclohexyl)-4H,6H-2,3,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl ester (0.19 g, 0.46 mmol) in dry tetrahydrofuran (5 ml) was added a 2M phenyl magnesium chloride solution in tetrahydrofuran (0.24 ml, 0.48 mmol) at room temperature. After stirring for 2 h the reaction mixture was quenched with aqueous saturated ammonium chloride solution and extracted with three portions of tert-butyl methyl ether. The combined organic layers were washed with one portion of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Flash-chromatography with n-heptane/ethyl acetate as eluent gave the title compound (0.094 g, 42%) as white solid. MS m/e: 495 ([[M+H]]+)
Reaction SMILES: C(O)(=O)C.[NH2:5][C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[SH:13].[OH:14][C:15]1[CH:16]=[C:17]([CH:20]=[C:21]([OH:23])[CH:22]=1)[CH:18]=O.C([O-])(=O)C.[Na+]>O.C(OCC)(=O)C>[Cl:12][C:10]1[CH:9]=[CH:8][C:7]2[S:13][C:18]([C:17]3[CH:20]=[C:21]([OH:23])[CH:22]=[C:15]([OH:14])[CH:16]=3)=[N:5][C:6]=2[CH:11]=1
Reactant: O=Cc1cc(O)cc(O)c1
Reactant: Nc1cc(Cl)ccc1S
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: O
Product: Oc1cc(O)cc(-c2nc3cc(Cl)ccc3s2)c1
Yield: 52.5 %

Procedure:
In an acetic acid (0.6 mL) solvent, a mixture including 2-amino-4-chlorobenzenethiol (100 mg, 0.44 mmol), 3,5-dihydroxybenzaldehyde (60 mg, 0.44 mmol), and sodium acetate (107 mg, 1.30 mmol) was refluxed for 7 hours. After cooling, the reaction mixture was distributed between ethyl acetate and water, and an organic layer was dried by using MgSO4, filtered, and evaporated under reduced pressure. The residual was purified by silica gel column chromatography using hexane and ethyl acetate (2:1) as a developer to obtain a solid Compound 90 (64.2 mg, 34.7%).
Reaction SMILES: [C:1]([C:4]1[N:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:7][C:8]=1[CH3:9])(=[O:3])[CH3:2].[Br:16]Br.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Br:16][CH2:2][C:1]([C:4]1[N:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:7][C:8]=1[CH3:9])=[O:3]
Reactant: CC(=O)c1nc(-c2ccccc2)oc1C
Reactant: BrBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: Cc1oc(-c2ccccc2)nc1C(=O)CBr
Temperature: 55 °C
Yield: 86.8 %

Procedure:
To a stirred solution of 4-acetyl-5-methyl-2-phenyloxazole (12.0 g) in chloroform (100 ml) was added at 50° C. a solution of bromine (10.5 g) in chloroform (10 ml). The mixture was further heated at 55° C. for 30 minutes and poured into saturated aqueous sodium bicarbonate solution (500 ml). The chloroform layer was separated and the aqueous layer was extracted with chloroform. The conbined chloroform layer was washed with water and dried (MgSO4). Evaporation of the solvent gave 4-bromoacetyl-5-methyl-2-phenyloxazole as crystals (14.5 g, 86.3%). Recrystallization from ethyl ether-hexane gave colorless rods, mp 88°-89° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]1[C:17]2[C:12](=[CH:13][C:14]([F:19])=[C:15]([F:18])[CH:16]=2)[C:11](=[O:20])[C:10]([C:21]([O:23]CC)=[O:22])=[CH:9]1.O.Cl>C(O)C>[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]1[C:17]2[C:12](=[CH:13][C:14]([F:19])=[C:15]([F:18])[CH:16]=2)[C:11](=[O:20])[C:10]([C:21]([OH:23])=[O:22])=[CH:9]1
Reactant: CCOC(=O)c1cn(-c2ccncc2F)c2cc(F)c(F)cc2c1=O
Agent: Cl
Solvent: O
Solvent: CCO
Product: O=C(O)c1cn(-c2ccncc2F)c2cc(F)c(F)cc2c1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.4 %

Procedure:
5 g of ethyl 1-(3-fluoro-4-pyridyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate is added with 20 ml of water, 30 ml of ethanol and 15 ml of conc. hydrochloric acid and refluxed for 8 hours. After cooling to room temperature and standing for 2 hours, filtering and drying are carried out to obtain 4.2 g of the desired compound.
Reaction SMILES: F[B-](F)(F)F.C([O+:8]([CH2:11][CH3:12])[CH2:9][CH3:10])C.[C:13]([C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:36]2C(=O)C[CH2:39][CH2:38][C:37]=2[OH:43])[NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=2)=[O:24])=[C:17]([F:44])[CH:16]=1)#[N:14].C(N(CC)C(C)C)(C)C.O>ClCCl>[C:13]([C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:36]2[C:37](=[O:43])[CH2:38][CH2:39][CH2:12][C:11]=2[O:8][CH2:9][CH3:10])[NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:33])([F:34])[F:35])[CH:27]=2)=[O:24])=[C:17]([F:44])[CH:16]=1)#[N:14]
Reactant: N#Cc1ccc(C(NC(=O)Nc2cccc(C(F)(F)F)c2)C2=C(O)CCCC2=O)c(F)c1
Reactant: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: CCOC1=C(C(NC(=O)Nc2cccc(C(F)(F)F)c2)c2ccc(C#N)cc2F)C(=O)CCC1

Procedure:
Triethyloxonium tetrafluoroborate (1.60 g, 8.42 mmol) is added to a solution of 1-((4-cyano-2-fluorophenyl)(2-hydroxy-6-oxocyclohex-1-enyl)methyl)-3-(3-(trifluoromethyl)phenyl)urea (intermediate 40 1.80 g, 4.02 mmol) and N,N-diisopropylethylamine (1.60 mL, 9.2 mmol) in dichloromethane (15 mL), and the mixture is stirred at room temperature for 20 min Water is added, and the phases are separated. The organic layer is dried over Na2SO4 and concentrated under reduced pressure. Yield: 1.82 g; ESI mass spectrum [M+H]+=476, Retention time HPLC: 1.11 min (Z018_S04).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([OH:14])=O)[CH:6]=[N:5]2.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:28][C@H:29]1[CH2:34][CH2:33][C@H:32]([NH2:35])[CH2:31][CH2:30]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:28][C@H:29]1[CH2:34][CH2:33][C@H:32]([NH:35][C:12]([C:7]2[CH:6]=[N:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=3)[N:8]=2)=[O:14])[CH2:31][CH2:30]1
Reactant: O=C(O)c1cnc2cc(F)ccc2n1
Reactant: C[C@H]1CC[C@H](N)CC1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H]1CC[C@H](NC(=O)c2cnc3cc(F)ccc3n2)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 6-fluoroquinoxaline-2-carboxylic acid (35 mg, 0.18 mmol) in dimethylformamide (4 mL) was treated with 1,1′-carbonyldiimidazole (29 mg, 0.18 mmol) and the reaction stirred for 16 hours at ambient temperature. After this time the reaction mixture was treated with trans-4-methylcyclohexylamine hydrochloride (27 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.05 mL, 0.29 mmol) and the reaction stirred 2 hours at ambient temperature. The solvent was evaporated to a solid (700 mg). The solid was dissolved in chloroform (10 mL) and added to diethyl ether (30 mL) The organic solution was washed with water (1×25 mL) and brine. The remaining organic solution was dried over anhydrous MgSO4, filtered, and concentrated to a solid (35 mg) HPLC (10 micron silica, 250×20 mm i.d.) of this material using a gradient of chloroform to 10% ethanol (in chloroform) afforded 20 mg (39%) of 434:
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.C([NH:8][C@@H:9]1[C:40](=[O:41])[N:11]2[C:12]([C:24]([O:26][CH:27]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[C:13]([CH2:16][S:17][C:18]3[S:19][C:20]([CH3:23])=[N:21][N:22]=3)[CH2:14][S:15][C@H:10]12)=O>CO>[ClH:3].[NH2:8][C@@H:9]1[C:40](=[O:41])[N:11]2[C:12]([C:24]([O:26][CH:27]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[C:13]([CH2:16][S:17][C:18]3[S:19][C:20]([CH3:23])=[N:21][N:22]=3)[CH2:14][S:15][C@H:10]12
Reactant: Cc1nnc(SCC2=C(C(=O)OC(c3ccccc3)c3ccccc3)N3C(=O)[C@@H](NC=O)[C@H]3SC2)s1
Reactant: O=P(Cl)(Cl)Cl
Solvent: CO
Product: Cc1nnc(SCC2=C(C(=O)OC(c3ccccc3)c3ccccc3)N3C(=O)[C@@H](N)[C@H]3SC2)s1
Product: Cl

Procedure:
Phosphorus oxychloride (1.8 ml.) was added dropwise during 2 minutes to a stirred and cooled (0°) suspension of diphenylmethyl 7β-formamido-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethylceph-3-em-4-carboxylate (4.1 g) in dry methanol. After 30 minutes the yellow solution was concentrated under reduced pressure. Ethyl acetate was added to the residue and the resulting solid was collected and washed with ether to give the title hydrochloride λmax. (EtOH) 266 nm (ε11,300), νmax. (Nujol) include 2590 (NH3+), 1778 (β-lactam) and 1710 cm.-1 (ester), τ values (DMSO-d6) include 0.50 (broad m; NH3), 2.3-2.7 (m; phenyl protons), 3.02 (s; CHPh2), 4.66+4.76 (m; C-7 H and C-6 H), 5.39+5.69 (2ds, branches of quartet, J 13 Hz; C-3 CH2S). 6.15 (singlet; C-2 CH2 ) and 7.36 (singlet; CH3).
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[NH:9][N:8]=[C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])[C:13]3([CH3:22])[S:20][CH3:21])[CH2:6][S:5]1.[C:23](Cl)(=[O:25])[CH3:24].C(OC(=O)C)C>CN(C=O)C>[C:23]([N:15]1[C:16]2[C:12](=[CH:11][C:10]([C:7]3[CH2:6][S:5][C:4](=[O:3])[NH:9][N:8]=3)=[CH:18][CH:17]=2)[C:13]([CH3:22])([S:20][CH3:21])[C:14]1=[O:19])(=[O:25])[CH3:24]
Reactant: CC(=O)Cl
Reactant: CSC1(C)C(=O)Nc2ccc(C3=NNC(=O)SC3)cc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CSC1(C)C(=O)N(C(C)=O)c2ccc(C3=NNC(=O)SC3)cc21
Temperature: 5 °C
Reaction time: 0.5 h

Procedure:
0.131 g sodium hydride from a 55% dispersion in mineral oil was added during 0.5 hr to a solution of 0.921 g of 1,3-dihydro-5-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-3-methyl-3-methylthio-2H-indol-2-one (compound of Example 1) in 25 ml DMF at 5° C. The mixture was stirred for 0.5 hr at 5° C. then 0.5 hr at 20° C. and cooled at 5° C. 0.215 ml of acetyl chloride in 1 ml DMF was added dropwise under stirring. The mixture was stirred for 0.5 hr at 5° C. then 1.5 hrs at 20° C. 250 ml ethylacetate was added and the corresponding organic solution was washed with water, dried and evaporated to dryness. The residual oil was purified by chromatography on silica (methylene chloride-ethylacetate: 9/1) to yield 0.4 g of white crystalline compound.
Reaction SMILES: [N+](C1C=C(S(CC[O:15][C:16](=[O:63])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:62])[CH2:24][O:25][C:26]2[CH:31]=[C:30]([CH3:32])[C:29]([S:33]([N:36]3[C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=4[N:38]=[C:37]3[S:45]([CH2:47][C:48]3[C:53]([CH3:54])=[C:52]([O:55][CH2:56][C:57]([F:60])([F:59])[F:58])[CH:51]=[CH:50][N:49]=3)=[O:46])(=[O:35])=[O:34])=[C:28]([CH3:61])[CH:27]=2)(=O)=O)C=CC=1)([O-])=O.C([O-])(O)=O.[Na+:68]>C1COCC1.O>[Na+:68].[CH3:32][C:30]1[CH:31]=[C:26]([CH:27]=[C:28]([CH3:61])[C:29]=1[S:33]([N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[C:37]1[S:45]([CH2:47][C:48]1[C:53]([CH3:54])=[C:52]([O:55][CH2:56][C:57]([F:58])([F:59])[F:60])[CH:51]=[CH:50][N:49]=1)=[O:46])(=[O:35])=[O:34])[O:25][CH2:24][C:23]([NH:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][C:16]([O-:63])=[O:15])=[O:62]
Reactant: Cc1cc(OCC(=O)NCCCCCC(=O)OCCS(=O)(=O)c2cccc([N+](=O)[O-])c2)cc(C)c1S(=O)(=O)n1c(S(=O)Cc2nccc(OCC(F)(F)F)c2C)nc2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(OCC(=O)NCCCCCC(=O)[O-])cc(C)c1S(=O)(=O)n1c(S(=O)Cc2nccc(OCC(F)(F)F)c2C)nc2ccccc21
Yield: 50.6 %

Procedure:
A solution of 6-[2-(3,5-dimethyl-4-{2-[3-methyl-4-(2,2,2-trifluoroethoxy)-pyridin-2-ylmethanesulfinyl]-benzimdazole-1-sulfonyl}phenoxy)acetylamino]hexanoic acid 2-(3-nitro-benzenesulfonyl)ethyl ester (Intermediate 18, 420 mg, 0.45 mmol) and of NaHCO3 (42 mg, 0.49 mmol) in THF-H2O (6 mL-3 mL) was heated to 70° C. for 1 h. Then volatile materials were removed, the residual gummy oil was dissolved in CH2Cl2 and the mixture was filtered to remove un-dissolved solid. The filtrate was concentrated to dryness and the residual semi-solid was treated with diethyl ether to precipitate a solid which was briefly treated with CH3CN. The solid was collected from CH3CN suspension by filtration to give Compound 6 (170 mg 50%) as a white solid.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([S:11](=[O:30])(=[O:29])[N:12]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=3[O:27][CH3:28])[C:13]3[S:17][N:16]=[CH:15][N:14]=3)=[CH:8][CH:9]=2)[N:4]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:3]=1.[CH3:38][N:39]1[C:43]([C:44]2[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][C:45]=2B(O)O)=[CH:42][CH:41]=[N:40]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:28][O:27][C:20]1[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:19]=1[CH2:18][N:12]([C:13]1[S:17][N:16]=[CH:15][N:14]=1)[S:11]([C:7]1[N:6]=[C:5]2[N:4]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH:3]=[C:2]([C:45]3[CH:46]=[CH:47][C:48]([C:50]([F:53])([F:51])[F:52])=[CH:49][C:44]=3[C:43]3[N:39]([CH3:38])[N:40]=[CH:41][CH:42]=3)[C:10]2=[CH:9][CH:8]=1)(=[O:29])=[O:30]
Reactant: Cn1nccc1-c1cc(C(F)(F)F)ccc1B(O)O
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc3c(Br)cn(C(=O)OC(C)(C)C)c3n2)c(OC)c1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc3c(-c4ccc(C(F)(F)F)cc4-c4ccnn4C)cn(C(=O)OC(C)(C)C)c3n2)c(OC)c1
Temperature: 90 °C
Yield: 71.3 %

Procedure:
A vial was charged with tert-butyl 3-bromo-6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (531.8 mg, 0.871 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (306 mg, 1.132 mmol), potassium phosphate (555 mg, 2.61 mmol), and Pd(AmPhos)2Cl2 (30.8 mg, 0.044 mmol). 1,4-Dioxane (2178 μl) and water (726 μl) were added in sequence. The vial was sealed and heated in a microwave reactor for 30 min at 90° C. The organic layer was removed via pipette, and the aq. layer was extracted with EtOAc (2×). The combined organic extracts were concentrated in vacuo. The crude product was purified by chromatography on silica gel (0 to 50% EtOAc/Heptane) to give tert-butyl 6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (469 mg, 0.621 mmol, 71.2% yield) as a white solid. m/z (ESI) 756.2 (M+H)+.
Reaction SMILES: [ClH:1].O1CCOCC1.OC(C(F)(F)F)=O.[F:15][C:16]1[CH:44]=[CH:43][CH:42]=[CH:41][C:17]=1[C:18]([N:20]1[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH:21]1[CH2:33][O:34][C:35]1[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=1)=[O:19]>CO>[ClH:1].[ClH:1].[F:15][C:16]1[CH:44]=[CH:43][CH:42]=[CH:41][C:17]=1[C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH:21]1[CH2:33][O:34][C:35]1[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=1)=[O:19]
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)c2ccccc2F)C(COc2cccnc2)C1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: O=C(c1ccccc1F)N1CCNCC1COc1cccnc1
Reaction time: 1 h
Yield: 86 %

Procedure:
4 M HCl in 1,4-dioxane (6 mL, 24 mmol) was added to a solution of tert-butyl 4-(2-fluorobenzoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate TFA salt (26 mg, 0.050 mmol) in MeOH (1 mL). After 1 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient). The desired chromatography fractions were concentrated under reduced pressure, dissolved in MeOH (1 mL), and treated with 4 M HCl in 1,4-dioxane. This was concentrated under reduced pressure, yielding 16.3 mg (86%) of the title compound as an off-white solid. LC-MS: RT=3.00 min, [M+H]+=316.3.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][CH:13]=[N:12][C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:18]N1C(=O)CCC1=O>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][CH:13]=[N:12][C:11]=2[N:10]=[C:9]1[Cl:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: O=c1[nH]cnc2ncn(Cc3ccccc3)c12
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=c1[nH]cnc2nc(Cl)n(Cc3ccccc3)c12
Reaction time: 8 h
Yield: 41.5 %

Procedure:
12.748 g of 7-benzyl-1,7-dihydropurin-6-one was dissolved in 150 ml of N,N-dimethylformamide, and 7.9 g of N-chlorosuccinimide was added thereto. The reaction solution was stirred overnight, and then diluted with ethyl acetate. The solution was washed with water and 1N hydrochloric acid, and dried over anhydrous magnesium sulfate. The solution was filtered, and the filtrate was concentrated to give 6.103 g of 7-benzyl-8-chloro-1,7-dihydropurin-6-one. This compound was combined with 20 g of t-butyl piperazine-1-carboxylate, and the mixture was heated at 150° C. After being stirred for one hour, the reaction mixture was combined with ethyl acetate and water, and partitioned. The organic layer was washed with 1N hydrochloric acid, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated. The residue was purified by silica gel column chromatography. Thus, 1.539 g of the title compound was obtained from the fraction eluted with ethyl acetate-methanol (10:1).
Reaction SMILES: [CH3:1][N:2]1[CH2:22][CH2:21][C:5]2[N:6]([CH2:14][CH2:15][C:16](OCC)=[O:17])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[CH2:23]([NH2:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([NH:30][C:16](=[O:17])[CH2:15][CH2:14][N:6]1[C:7]2[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=2[C:4]2[CH2:3][N:2]([CH3:1])[CH2:22][CH2:21][C:5]1=2)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CCOC(=O)CCn1c2c(c3cc(C)ccc31)CN(C)CC2
Reactant: NCc1ccccc1
Product: Cc1ccc2c(c1)c1c(n2CCC(=O)NCc2ccccc2)CCN(C)C1
Temperature: 100 °C
Yield: 29.16 %

Procedure:
Ethyl 3-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)propanoate (200 mg, 0.66 mmol) was added to benzylamine (2.0 ml, excess) and the reaction mixture was heated at 100° C. for 14 h. After completion of the reaction (monitored by LCMS) it was concentrated and basified with aqueous saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was concentrated to dryness and the crude obtained was purified by silica gel chromatography (Eluent: 10% MeOH in dichloromethane) to get 70 mg (yield: 29.16%) of N-benzyl-3-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)propanamide as a free base. To the free base (40 mg, 0.11 mmol) dissolved in THF (5.0 ml), oxalic acid (13 mg, 0.10 mmol) in THF (5.0 ml) was added slowly, the mixture was stirred at RT for 20 minutes and the solid obtained was filtered, washed with ether and dried to get 35 mg (yield: 71.4%) of N-benzyl-3-(1,2,3,4-tetrahydro-2,8-dimethylpyrid[4,3-b]indol-5-yl)propanamide as oxalate salt. 1H NMR (DMSO) 7.50-7.30 (t, 3H), 7.20-7.10 (m, 3H), 7.0-6.90 (m, 2H), 4.40-4.30 (m, 4H), 4.30-4.20 (t, 2H), 4.0 (s, 2H), 3.10 (m, 2H), 2.90 (s, 3H), 2.60-2.50 (t, 3H), 2.40 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:9]/[C:10](/[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[N:11]\[OH:12])=[CH:4][CH:3]=1.[CH2:25]([S:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)(=[O:29])=[O:28])[CH3:26]>>[CH2:25]([S:27]([C:30]1[CH:35]=[CH:34][C:33]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:9]/[C:10](/[C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[N:11]\[OH:12])=[CH:4][CH:3]=2)=[CH:32][CH:31]=1)(=[O:28])=[O:29])[CH3:26]
Reactant: O/N=C(\CC(c1ccccc1)c1ccc(Br)cc1)c1ccncc1
Reactant: CCS(=O)(=O)c1ccc(B(O)O)cc1
Product: CCS(=O)(=O)c1ccc(-c2ccc(C(C/C(=N\O)c3ccncc3)c3ccccc3)cc2)cc1

Procedure:
In analogy to example 22, from (E)-3-(4-bromo-phenyl)-3-phenyl-1-pyridin-4-yl-propan-1-one oxime (example 5) and 4-(ethanesulfonyl)benzeneboronic acid was prepared the title compound as a white foam, MS (ESI+): m/z=471.1 ([M+H]+).
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH2:2][OH:3].[CH3:6][Si:7](Cl)([CH3:9])[CH3:8]>O1CCCC1>[CH3:6][Si:7]([CH3:9])([CH3:8])[O:4][C:1]([O:5][Si:7]([CH3:9])([CH3:8])[CH3:6])=[CH:2][O:3][Si:7]([CH3:9])([CH3:8])[CH3:6]
Reactant: C[Si](C)(C)Cl
Reactant: O=C(O)CO
Solvent: C1CCOC1
Product: C[Si](C)(C)OC=C(O[Si](C)(C)C)O[Si](C)(C)C

Procedure:
The reagent 1,1,2-tris-trimethylsilyloxyethylene (80) and its use for the conversion of acid chlorides to hydroxyketone (for example 96 to 98 and 90 to 92) are claimed in this invention. The reagent preparation is described hereinbelow in Flowsheet M. The reaction of glycolic acid with 1,1,1,-3,3,3-hexamethyldisilazane and trimethylsilylchloride in pyridine gives bis-trimethylsilated glycolic acid (113). Addition of (113) to a tetrahydrofuran solution of one equivalent of lithium 1,1,1,3,3,3-hexamethyldisilazane amide at -78° C. generates a lithium enolate which is trapped with trimethylsilylchloride to produce the desired reagent (80). ##STR97##
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.Cl[C:26](Cl)([O:28][C:29](=[O:35])OC(Cl)(Cl)Cl)Cl.[CH:37]1(CO)[CH2:40][CH2:39][CH2:38]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:22]([CH3:23])=[CH:21][C:19]([NH:20][C:29](=[O:35])[O:28][CH2:26][CH:37]2[CH2:40][CH2:39][CH2:38]2)=[C:18]([CH3:24])[CH:17]=1
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Reactant: OCC1CCC1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3cc(C)c(NC(=O)OCC4CCC4)cc3C)c2cc1OC
Yield: 90.7 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclobutylmethanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 86%).