Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[F:18])[C:12]([OH:14])=O)[CH:5]=[CH:4][N:3]=1.[F:19][C:20]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:21]=1[NH2:22].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[F:18])[C:12]([NH:22][C:21]2[CH:23]=[C:24]([CH3:27])[CH:25]=[CH:26][C:20]=2[F:19])=[O:14])[CH:5]=[CH:4][N:3]=1
Reactant: O=C(O)c1ccc(F)c(Oc2ccnc(Cl)c2)c1
Reactant: Cc1ccc(F)c(N)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: Cc1ccc(F)c(NC(=O)c2ccc(F)c(Oc3ccnc(Cl)c3)c2)c1

Procedure:
A solution of 3-(2-Chloropyridin-4-yloxy)-4-fluorobenzoic acid (2.22 g, 8.29 mmol), 2-fluoro-5-methylaniline (1.56 g, 12.4 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 3.78 g, 9.95 mmol) and N-methylmorpholine (2.00 mL, 18.2 mmol) in dimethylformamide (22 mL) was heated at 90° C. for 2 h. The solvent was evaporated in vacuo at 50° C. To the residue was added water resulting in a thick oil. The water was decanted and the oil dissolved in EtOAc then extracted twice with water, 1M hydrochloric acid and brine. The organic layer was dried (MgSO4), filtered and evaporated to crude 6 (3.37 g). Trituration with dichloromethane (25 mL) gave 3-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide as white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=[O:5].[F:11][C:12]1[CH:17]=[CH:16][C:15]([Mg]Br)=[CH:14][CH:13]=1>C(OCC)(=O)C>[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]([C:15]1[CH:16]=[CH:17][C:12]([F:11])=[CH:13][CH:14]=1)[OH:5]
Reactant: Fc1ccc([Mg]Br)cc1
Reactant: Nc1cccc(Cl)c1C=O
Solvent: CCOC(C)=O
Product: Nc1cccc(Cl)c1C(O)c1ccc(F)cc1
Yield: 57 %

Procedure:
This compound was prepared using General Method 1 (EXAMPLE 1) from 2-amino-6-chlorobenzaldehyde (0.30 g, 1.9 mmol) and 4-fluorophenylmagnesium bromide (1 M in THF, 3.8 mL) to afford 0.28 g (57%) of (±)-(2-amino-6-chlorophenyl)-(4-fluorophenyl)methanol after flash chromatography (4:1 hexanes:ethyl acetate).
Reaction SMILES: Cl.[O:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH:7]([NH2:10])[C:8]#[N:9].[CH3:11][C:12]1[C:16]([C:17](Cl)=[O:18])=[CH:15][S:14][N:13]=1>N1C=CC=CC=1>[C:8]([CH:7]([NH:10][C:17]([C:16]1[C:12]([CH3:11])=[N:13][S:14][CH:15]=1)=[O:18])[C:3]1[O:2][CH:6]=[CH:5][CH:4]=1)#[N:9]
Reactant: Cc1nscc1C(=O)Cl
Reactant: N#CC(N)c1ccco1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1nscc1C(=O)NC(C#N)c1ccco1
Temperature: 25 °C

Procedure:
1.2 g of alpha-(2-furyl)-alpha-aminoacetonitrile hydrochloride was dissolved in 10 ml of pyridine, and with stirring at room temperature, 1.1 g of 3-methylisothiazole-4-carboxylic acid chloride was added dropwise. After the dropwise addition, the mixture was stirred for 1 hour, and distilled under reduced pressure to remove pyridine. The residue was dissolved in ethyl acetate, separated, washed with water, and dried over sodium sulfate. The ethyl acetate layer was distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with benzene-ethyl acetate gave 1.2 g (yield of the desired N-(alpha-cyanofurfuryl)-3-methylisothiazole-4-carboxylic acid amide.
Reaction SMILES: [O:1]=[C:2]([CH3:12])[CH2:3][CH2:4][CH2:5][C:6]#[C:7][CH2:8][CH2:9][CH2:10][OH:11].CC(C)=[O:15].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[O:1]=[C:2]([CH3:12])[CH2:3][CH2:4][CH2:5][C:6]#[C:7][CH2:8][CH2:9][C:10]([OH:15])=[O:11]
Reactant: CC(C)=O
Reactant: CC(=O)CCCC#CCCCO
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: CC(=O)CCCC#CCCC(=O)O
Temperature: 0 °C

Procedure:
20 Parts of 9-oxodec-4-yn-1-ol of Example 4 is dissolved in 200 parts by volume of acetone and cooled to 0° C. The cold solution is stirred and treated dropwise with 90 parts by volume of 2.67 molar Jones reagent (chromic acid in sulfuric acid and water). The acetone solution is decanted from the solid chromium salts, which are then rinsed with fresh acetone. The acetone solutions are combined and poured into a mixture of ether and water. The ether layer is separated from the water, washed once with water, and then extracted three times with 5% potassium carbonate solution. The alkaline extracts are combined, acidified with concentrated hydrochloric acid and extracted twice with ether and once with ethyl acetate. The extracts are combined, dried over sodium sulfate, and stripped of solvent to give the pure product, 9-oxodec-4-ynoic acid.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:11]3[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=3)[N:9]=[CH:10][C:3]=12.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([SH:34])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([S:34][C:2]2[N:7]=[CH:6][N:5]=[C:4]3[N:8]([C:11]4[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=4)[N:9]=[CH:10][C:3]=23)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]
Reactant: CS(=O)(=O)c1ccc(-n2ncc3c(Cl)ncnc32)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(S)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(Sc2ncnc3c2cnn3-c2ccc(S(C)(=O)=O)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 43.8 %

Procedure:
4-Chloro-1-(4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine (1.23 mmol, 250 mg), 4-mercapto-piperidine-1-carboxylic acid tert-butyl ester (1.23 mmol, 268 mg) and potassium carbonate (1.4 mmol, 203 mg) were dissolved in DMF (10 mL) and stirred for 60 minutes at room temperature. Its progress was followed by thin layer chromatography and LCMS. The reaction mixture was quenched with water followed by an extraction with ethylacetate. Removal of organic solvents in vacuo and purification by column chromatography provided compound A102 as a white solid (264 mg, 66%). 1H NMR (400MHz, CDCl3) δ (ppm): 8.83 (s, 1H); 8.61 (d, 2H); 8.24 (s, 1H); 8.11 (d, 2H); 4.42 (h, 1H); 4.00 (m, 2H); 3.20 (m, 2H); 3.15 (s, 3H); 2.19 (m, 2H); 1.77 (m, 2H); 1.46 (s, 9H). LCMS (ESI), m/z 490.3 (MH+, 100%)
Reaction SMILES: Cl[C:2]1[C:7]([O:8][CH2:9][CH3:10])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:11][O-:12].[Na+]>O>[CH2:9]([O:8][C:7]1[C:2]([O:12][CH3:11])=[N:3][CH:4]=[CH:5][CH:6]=1)[CH3:10]
Reactant: C[O-]
Reactant: CCOc1cccnc1Cl
Agent: [Na+]
Solvent: O
Product: CCOc1cccnc1OC
Yield: 94.5 %

Procedure:
A solution of 2-chloro-3-ethoxy-pyridine (3.0 g, 19.0 mmol, 1.0 equiv) and sodium methoxide (8.8 mL, 47.5 mmol, 2.5 equiv, 5.4 M solution in methanol) was heated to 100° C. under microwave irradiation for 20 min. The crude reaction mixture was poured into water (100 mL) and extracted with dichloromethane (3×100 mL). The combined organic phases were dried over MgSO4 and the solvent removed by evaporation under reduced pressure to yield 2.75 g (95%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.40 (t, J=7.0 Hz, 3H), 3.94 (s, 3H), 4.02 (q, J=7.0 Hz, 2H), 6.75 (dd, J=7.8 Hz, J=5.0 Hz, 1H), 6.96 (dd, J=7.8 Hz, J=1.5 Hz, 1H), 7.65 (dd, J=5.0 Hz, 1=1.5 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 13.62, 52.53, 63.25, 115.69, 117.53, 136.13, 142.45, 153.84. MS (ISP): 153.8 [M+H]+.
Reaction SMILES: Br[CH2:2][C:3]1[CH:24]=[CH:23][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[CH:11]=2)=[O:8])=[CH:5][CH:4]=1.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>CS(C)=O>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:23]=[CH:24][C:3]([CH2:2][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[CH:4][CH:5]=2)=[CH:11][C:12]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1
Reactant: C1COCCN1
Reactant: O=C(Nc1ccc(Cl)c(-c2ccccn2)c1)c1ccc(CBr)cc1
Solvent: CS(C)=O
Product: O=C(Nc1ccc(Cl)c(-c2ccccn2)c1)c1ccc(CN2CCOCC2)cc1

Procedure:
4-(bromomethyl)-N-(4-chloro-3-(pyridin-2-yl)phenyl)benzamide (85 mg) was dissolved in DMSO (1 mL) and stirred for 1 h with morpholine. The reaction mixture was concentrated, and the crude residue was purified by reverse phase HPLC to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(morpholinomethyl)benzamide. MS (Q1) 408.4 (M)+.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[C:7]2=[O:12].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[CH:23][C:22]=1[C:31]([F:34])([F:33])[F:32].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28]([NH:1][C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:7]3=[O:12])=[O:29])=[CH:23][C:22]=1[C:31]([F:32])([F:33])[F:34]
Reactant: Nc1cccc2c(=O)n(Cc3ccccn3)ccc12
Reactant: O=C(O)Cc1ccc(Cl)c(C(F)(F)F)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Cc1ccc(Cl)c(C(F)(F)F)c1)Nc1cccc2c(=O)n(Cc3ccccn3)ccc12
Temperature: 50 °C
Reaction time: 16 h
Yield: 71.1 %

Procedure:
To a solution of 5-amino-2-(pyridin-2-ylmethyl)isoquinolin-1(2H)-one (100.00 mg, 0.4 mmol) in N,N-dimethylformamide (0.7 mL, 0.009 mol) was added 2-(4-chloro-3-(trifluoromethyl)phenyl)acetic acid (190 mg, 0.000796 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (303 mg, 0.000796 mol) and N,N-diisopropylethylamine (277 uL, 0.00159 mol). The reaction mixture was stirred for 16 hours at 50° C. Checked LC/MS, the reaction was completed. The DMF reaction solution was directly applied to prep. HPLC to obtain the pure product (134.2 mg). MS m/z=472.3 (M+1). 1H NMR (DMSO) δ 10.13 (s, 1 H), 8.48 (d, J=4.8 Hz, 1 H), 8.06 (d, J=7/9 Hz, 1 H), 7.90 (s, 1 H), 7.84 (d, J=7.1 Hz, 1 H), 7.76 (td, J=7.7, 1.8 Hz, 1 H), 7.75-7.68 (m, 2 H), 7.63 (d, J=7.7 Hz, 1 H), 7.47 (t, J=7.9 Hz, 1 H), 7.32-7.22 (m, 2 H), 6.73 (d, J=7.6 Hz, 1 H), 5.28 (s, 2 H), 3.93 (s, 2 H).
Reaction SMILES: [NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].[C:8]([S:11][CH2:12][CH:13]([CH3:17])[C:14](Cl)=[O:15])(=[O:10])[CH3:9]>>[C:8]([S:11][CH2:12][CH:13]([CH3:17])[C:14]([NH:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4])=[O:15])(=[O:10])[CH3:9]
Reactant: CC(=O)SCC(C)C(=O)Cl
Reactant: N[C@@H](CO)C(=O)O
Product: CC(=O)SCC(C)C(=O)N[C@@H](CO)C(=O)O

Procedure:
Following the procedure of Example 16, L-serine is reacted with 3-acetylthio-2-methyl-propanoyl chloride to give (±)-N-[3-(acetylthio)-2-methyl -1-oxopropyl]-L-serine.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.C([O-])([O-])=O.[K+].[K+].CS([CH2:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][C:25]=1[CH3:29])(=O)=O.O>CN(C=O)C>[CH3:7][O:6][C:5]1[CH:4]=[C:3]([CH:11]=[CH:10][C:8]=1[O:9][CH2:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][C:25]=1[CH3:29])[CH:2]=[O:1]
Reactant: Cc1ncsc1CCS(C)(=O)=O
Reactant: COc1cc(C=O)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(C=O)ccc1OCCc1scnc1C
Temperature: 75 °C

Procedure:
Vanillin (2.9 mmol) was added to mixture of K2CO3 (14.5 mmol) and 5-(2-Methanesulfonyl-ethyl)-4-methyl-thiazole (5) (2.9 mmol) in DMF (0.2 M), and heated to 75° C. for 16 h. After cooling, water was added and aqueous mixture extracted 5 times with methylene chloride. The methylene chloride layers were combined and concentrated to afford the product (6).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].COC1C=C(OC)C=CC=1C[NH:10][CH:11]1[C:20]2[CH2:19][S:18][N:17]=[C:16]([N:21](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:15]3=[N:36][N:37]([CH2:39][C:40]4[C:45]([CH3:46])=[C:44]([O:47][CH3:48])[C:43]([CH3:49])=[CH:42][N:41]=4)[N:38]=[C:13]([C:14]=23)[CH2:12]1.N1C=CC=CC=1>ClCCl>[NH2:21][C:16]1[C:15]2[C:14]3[C:13](=[N:38][N:37]([CH2:39][C:40]4[C:45]([CH3:46])=[C:44]([O:47][CH3:48])[C:43]([CH3:49])=[CH:42][N:41]=4)[N:36]=2)[CH2:12][CH:11]([NH:10][C:1](=[O:3])[CH3:2])[C:20]=3[CH2:19][S:18][N:17]=1
Reactant: COc1ccc(CNC2CC3=NN(Cc4ncc(C)c(OC)c4C)N=C4C(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=NSCC2=C34)c(OC)c1
Reactant: CC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1c(C)cnc(CN2N=C3CC(NC(C)=O)C4=C3C(=N2)C(N)=NSC4)c1C
Reaction time: 3 h
Yield: 76 %

Procedure:
Acetyl chloride (18 μL) was added dropwise to a mixture composed of di-tert-butyl {8-[(2,4-dimethoxybenzyl)amino]-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7,8,9-tetrahydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-4-yl}imidodicarbonate of Example 42 (36 mg), pyridine (40 μL) and dehydrated dichloromethane (0.7 mL) under cooling in an ice bath. The ice bath was removed and the mixture was stirred for three hours. The reaction mixture was diluted with chloroform and then washed with a 0.2 N hydrochloric acid solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and dichloromethane (1 mL) and 1,3-dimethoxybenzene (12 μL) were added to the resulting residue. Then, trifluoroacetic acid (1 mL) was added and the mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in chloroform and sequentially washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel thin-layer chromatography (chloroform-methanol) to obtain the title compound (15.6 mg, 76%) as a solid.
Reaction SMILES: [C:1]1([C:7]2[S:8][CH2:9][CH:10]([C:12]([OH:14])=[O:13])[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:15]I>O1CCCC1>[C:1]1([C:7]2[S:8][CH2:9][C:10]([CH3:15])([C:12]([OH:14])=[O:13])[N:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)C1CSC(c2ccccc2)=N1
Reactant: CI
Solvent: C1CCOC1
Product: CC1(C(=O)O)CSC(c2ccccc2)=N1

Procedure:
Cysteine, benzonitrile, and 5 equivalents of triethylamine were refluxed in ethanol for 6-8 hours to obtain a 66-70% yield of 2-phenylthiazoline-4-carboxylic acid. The 2-phenylthiazoline-4 carboxylic acid was reacted with 2.05 equivalents of base and 1 equivalent of methyl iodide in tetrahydrofuran at 0° C. to form 2-phenyl-4-methylthiazoline-4 carboxylic acid. The 2-phenyl-4-methylthiazoline-4-carboxylic acid can be hydrolyzed with hydrochloride acid, thereby obtaining a mixture of (R)- and (S)-2-methylcysteine hydrochloride.
Reaction SMILES: CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]3[CH2:24][C:23]([O:25][C:26]4[C:35]5[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=5[CH:29]=[CH:28][CH:27]=4)=[CH:22][C:21]3=[O:36])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]2[CH2:24][C:23]([O:25][C:26]3[C:35]4[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=4[CH:29]=[CH:28][CH:27]=3)=[CH:22][C:21]2=[O:36])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]1
Reactant: CC(C)C[C@@H](C(=O)Nc1ccn(C[C@@H]2COC(C)(C)O2)n1)N1CC(Oc2cccc3c2CCCC3)=CC1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: CC(C)C[C@@H](C(=O)Nc1ccn(C[C@@H](O)CO)n1)N1CC(Oc2cccc3c2CCCC3)=CC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.5 %

Procedure:
A solution of (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (43 mg, 0.08 mmol) in methanol (1 mL) at 25° C. was treated with p-toluenesulfonic acid monohydrate (4 mg, 0.02 mmol). The reaction was stirred at 25° C. overnight. At this time, the reaction was concentrated in vacuo. The residue was diluted with dichloromethane (25 mL) and was washed with a saturated aqueous sodium bicarbonate solution (1×25 mL), water (1×25 mL) and a saturated aqueous sodium chloride solution (1×25 mL), dried over magnesium sulfate, filtered, rinsed with dichloromethane and concentrated in vacuo. Purification by Analogix flash chromatography (8 g, 1-10% methanol/dichloromethane) afforded (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (28 mg, 71%) as a white solid: HR-ES-MS m/z calculated for C26H34N4O5 [M+H]+ 483.2602, observed 483.2603; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 1.46 (br. s., 1H), 1.53-1.65 (m, 1H), 1.65-1.85 (m, 5H), 2.57 (br. s., 2H), 2.76 (br. s., 2H), 3.21-3.31 (m, 2H), 3.72-3.82 (m, 1H), 3.87 (dd, J=13.4, 7.5 Hz, 1H), 4.09 (dd, J=13.6, 4.0 Hz, 1H), 4.18 (d, J=18.3 Hz, 1H), 4.56 (d, J=18.3 Hz, 1H), 4.65 (s, 1H), 4.71 (t, J=5.4 Hz, 1H), 4.87 (dd, J=10.7, 4.9 Hz, 1H), 4.93 (d, J=5.1 Hz, 1H), 6.41 (d, J=2.1 Hz, 1H), 7.04 (d, J=7.7 Hz, 2H), 7.18 (t, J=7.7 Hz, 1H), 7.53 (d, J=2.1 Hz, 1H), 10.75 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH:17]([CH3:19])[CH3:18])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[C:20](Cl)(=[O:23])[CH2:21][CH3:22]>>[C:20]([NH:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH:17]([CH3:19])[CH3:18])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1)(=[O:23])[CH2:21][CH3:22]
Reactant: CC(C)N1CCC(c2c[nH]c3ccc(N)nc23)CC1
Reactant: CCC(=O)Cl
Product: CCC(=O)Nc1ccc2[nH]cc(C3CCN(C(C)C)CC3)c2n1
Yield: 636.1 %

Procedure:
Beginning with 0.10 gm (0.39 mMol) 5-amino-3-(1-isopropylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.040 mL (0.046 mMol) propionyl chloride, 0.092 gm (75%) of the title compound were prepared as an ivory foam essentially by the procedure described in Example 4. An analytical sample was crystallized from aqueous ethanol.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:18]=[CH:17][CH:16]=[CH:15]2)=[CH:10][C:9]=1[NH2:19])(C)(C)C.[CH2:21]([O:23][C:24]([C:26]1[N:27]=[CH:28][O:29][C:30]=1[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]2OC(C)(C)O[C:41](=[O:43])[CH:42]=2)[CH:32]=1)=[O:25])[CH3:22].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:21]([O:23][C:24]([C:26]1[N:27]=[CH:28][O:29][C:30]=1[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]2[CH2:42][C:41](=[O:43])[NH:19][C:9]3[CH:10]=[C:11]([N:14]4[CH:18]=[CH:17][CH:16]=[CH:15]4)[CH:12]=[CH:13][C:8]=3[N:7]=2)[CH:32]=1)=[O:25])[CH3:22]
Reactant: CCOC(=O)c1ncoc1-c1cccc(C2=CC(=O)OC(C)(C)O2)c1
Reactant: CC(C)(C)OC(=O)Nc1ccc(-n2cccc2)cc1N
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)c1ncoc1-c1cccc(C2=Nc3ccc(-n4cccc4)cc3NC(=O)C2)c1

Procedure:
The title compound was prepared from (2-amino-4-pyrrol-1-yl-phenyl)-carbamic acid tert.-butyl ester (Example J2) (164 mg) and 5-[3-(2,2-dimethyl-6-oxo-6H-[1,3]dioxin-4-yl)-phenyl]-oxazole-4-carboxylic acid ethyl ester (Example L6) (206 mg) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (63 mg).
Reaction SMILES: Cl[SiH:2](Cl)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:10]([C:26]1[CH:31]=[C:30]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:29]=[C:28]([C:36]([CH3:39])([CH3:38])[CH3:37])[C:27]=1[OH:40])[C:11]1[CH:16]=[C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:14]=[C:13]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:12]=1[OH:25].C(N(CC)CC)C>>[C:32]([C:30]1[CH:29]=[C:28]([C:36]([CH3:39])([CH3:38])[CH3:37])[C:27]2[O:40][SiH:2]([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[O:25][C:12]3[C:13]([C:21]([CH3:23])([CH3:22])[CH3:24])=[CH:14][C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:16][C:11]=3[CH2:10][C:26]=2[CH:31]=1)([CH3:35])([CH3:34])[CH3:33]
Reactant: Cl[SiH](Cl)c1ccccc1
Reactant: CC(C)(C)c1cc(Cc2cc(C(C)(C)C)cc(C(C)(C)C)c2O)c(O)c(C(C)(C)C)c1
Solvent: CCN(CC)CC
Product: CC(C)(C)c1cc2c(c(C(C)(C)C)c1)O[SiH](c1ccccc1)Oc1c(cc(C(C)(C)C)cc1C(C)(C)C)C2
Yield: 64.3 %

Procedure:
Utilizing the procedure of Example 1, this compound is prepared from 17.7 grams (0.1 mole) of dichlorophenylsilane, 42.5 grams (0.1 mole) of 2,2'-methylenebis(4,6-di-t-butylphenol) and 20.2 grams (0.20 mole) of triethylamine. Recrystallization twice from acetonitrile-toluene yields 34.0 grams (64% yield) of product as an off white powder, mp 153°-156° C.; IR: 2200 cm-1SiH.
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].[NH2:5][C:6]1[CH:21]=[CH:20][C:9]2[N:10]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[S:12][C:8]=2[CH:7]=1.O>O1CCOCC1>[N:5]([C:6]1[CH:21]=[CH:20][C:9]2[N:10]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[S:12][C:8]=2[CH:7]=1)=[C:1]=[S:2]
Reactant: Nc1ccc2nc(Oc3ccccc3)sc2c1
Reactant: S=C(Cl)Cl
Solvent: O
Solvent: C1COCCO1
Product: S=C=Nc1ccc2nc(Oc3ccccc3)sc2c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
An amount of 8.46 g of thiophosgene in a sulphonating flask is stirred into 500 ml of ice water. An addition is then made dropwise, in the course of 10 minutes, of a solution of 18 g of 6-amino-2-phenoxybenzothiazole in 100 ml of dioxane as well as 10 ml of water. The suspension is further stirred overnight at room temperature. The formed precipitate is separated and washed with water; the residue is dissolved in 100 ml of methylene chloride, and the solution dried over sodium sulphate. After chromatography with methylene chloride through aluminium oxide (neutral, activity stage III), an amount of 12.5 g. of 6-isothiocyano-2-phenoxybenzothiazole, M.P. 118° to 119°C, is obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([C:12]([C@H:14]3[O:19][CH2:18][C@H:17]([NH:20][CH2:21][C:22]4[CH:23]=[CH:24][C:25]5[S:26][CH2:27][C:28](=[O:32])[NH:29][C:30]=5[N:31]=4)[CH2:16][CH2:15]3)=O)[S:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.Cl.[NH2:34][OH:35]>N1C=CC=CC=1>[OH:35][N:34]=[C:12]([C:10]1[S:11][C:7]2[CH:6]=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:8]=2[N:9]=1)[C@H:14]1[O:19][CH2:18][C@H:17]([NH:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]3[S:26][CH2:27][C:28](=[O:32])[NH:29][C:30]=3[N:31]=2)[CH2:16][CH2:15]1
Reactant: COc1cccc2sc(C(=O)[C@@H]3CC[C@@H](NCc4ccc5c(n4)NC(=O)CS5)CO3)nc12
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Product: COc1cccc2sc(C(=NO)[C@@H]3CC[C@@H](NCc4ccc5c(n4)NC(=O)CS5)CO3)nc12
Yield: 20 %

Procedure:
A solution of (3R,6S)-6-{[6-(4-methoxy-benzothiazole-2-carbonyl)-tetrahydro-pyran-3-ylamino]-methyl}-4H-pyrido[3,2-b][1,4]thiazin-3-one (Example 29, 47 mg, 0.1 mmol), and hydroxylamine hydrochloride (5 eq) in pyridine (1 ml) was stirred at RT overnight. The mixture was concentrated in vacuo and partitioned between NH4OH and DCM. The organic layers were dried over MgSO4 and concentrated. Chromatography on SiO2 (EtOAc/MeOH 9:1 +1% NH4OH) gave the title compound as yellow solid (10 mg, 20%).