Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:34][C:35]1[N:36]=[N:37][CH:38]=[CH:39][N:40]=1>N1C=CC=CC=1>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:34][C:35]2[N:36]=[N:37][CH:38]=[CH:39][N:40]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(O)C(CC1CCCC1)c1ccc(Cl)c(Cl)c1
Reactant: Nc1nccnn1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: c1ccncc1
Product: O=C(Nc1nccnn1)C(CC1CCCC1)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 8 %

Procedure:
A solution of 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 38A, 400 mg, 1.40 mmol) in dry pyridine (5 mL) was treated with 1,3-dicyclohexylcarbodiimide (316 mg, 1.53 mmol). The reaction mixture was stirred at 25° C. for 3.5 h and then treated with 3-amino-1,2,4-triazine (296 mg, 3.08 mmol) and an additional amount of pyridine (1 mL). The reaction mixture was warmed at 100° C. for 20 h. The reaction mixture was concentrated in vacuo to remove pyridine. The resulting residue was diluted with ethyl acetate then filtered. The filtrate was washed with a 1N aqueous hydrochloric acid solution and washed with water. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-[1,2,4]triazin-3-yl-propionamide (40.9 mg, 8%) as a yellow-orange solid: mp 81-83° C.; EI-HRMS m/e calcd for C17H18Cl2N4O (M+) 364.0858, found 364.0857.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([OH:12])=O)[CH:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:44]([C:48]1[CH:64]=[CH:63][C:51]([CH2:52][NH:53][CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[C:58]([Cl:62])[CH:57]=2)=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C.O>[C:44]([C:48]1[CH:64]=[CH:63][C:51]([CH2:52][N:53]([CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[C:58]([Cl:62])[CH:57]=2)[C:10]([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[NH:1][CH:2]=[CH:3]3)=[O:12])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]
Reactant: O=C(O)c1cccc2cc[nH]c12
Reactant: CC(C)(C)c1ccc(CNCCc2cccc(Cl)c2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CC(C)(C)c1ccc(CN(CCc2cccc(Cl)c2)C(=O)c2cccc3cc[nH]c23)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 91.4 %

Procedure:
To a solution of 48 mg (0.3 mmol) of 1H-indole-7-carboxylic acid and 96 mg of TBTU (0.3 mmol) in 4 ml DMF, were added 0.26 ml (1.5 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 91 mg (0.3 mmol) (4-tert-butyl-benzyl)-[2-(3-chloro-phenyl)-ethyl]-amine in 1 ml DMF was added. After 2.5 h stirring at rt, the reaction mixture was diluted with 50 ml water and extracted with 2×50 ml EtOAc. The combined organic phases were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The yellow solid foam was purified by column chromatography (8 g silica gel; heptane/EtOAc 9:1) to give 122 mg (90%) of a white semisolid. MS (EI) 444.2 (M)+.
Reaction SMILES: O.[NH2:2][NH2:3].[F:4][C:5]1[CH:24]=[CH:23][C:8](/[CH:9]=[C:10]2\[O:11][C:12](=O)[C:13]3[C:18]\2=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][CH:14]=3)=[CH:7][C:6]=1[C:25]([N:27]1[CH2:32][CH2:31][CH:30]([O:33][CH3:34])[CH2:29][CH2:28]1)=[O:26].CN(C)C=O>O>[F:4][C:5]1[CH:24]=[CH:23][C:8]([CH2:9][C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[N+:19]([O-:21])=[O:20])[C:12](=[O:11])[NH:3][N:2]=2)=[CH:7][C:6]=1[C:25]([N:27]1[CH2:32][CH2:31][CH:30]([O:33][CH3:34])[CH2:29][CH2:28]1)=[O:26]
Reactant: NN
Reactant: COC1CCN(C(=O)c2cc(/C=C3\OC(=O)c4cccc([N+](=O)[O-])c43)ccc2F)CC1
Solvent: O
Solvent: CN(C)C=O
Product: COC1CCN(C(=O)c2cc(Cc3n[nH]c(=O)c4cccc([N+](=O)[O-])c34)ccc2F)CC1
Temperature: 100 °C
Reaction time: 18 h
Yield: 75.7 %

Procedure:
Hydrazine hydrate (0.046 mL, 0.94 mmol) was added in one portion to (Z)-3-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzylidene)-4-nitroisobenzofuran-1(3H)-one (44) (50 mg, 0.12 mmol) and N,N-Dimethylformamide (0.045 mL, 0.59 mmol) in water (2 mL) at 25° C. under air. The resulting mixture was stirred at 100° C. for 18 hours. The mixture was cooled to ambient temperature and the solvent evaporated to give crude desired product as a pale brown solid (40.0 mg, 77% yield); 1H NMR: (400.132 MHz, DMSO) δ 1.23-1.33 (1H, m), 1.36-1.50 (1H, m), 1.65-1.72 (1H, m), 1.79-1.92 (1H, m), 3.25-3.27 (4H, m), 3.33 (3H, s), 3.82-3.97 (1H, m), 4.10 (2H, s), 7.10-7.21 (3H, m), 7.99-8.03 (1H, m), 8.27 (1H, d), 8.59 (1H, d); m/z (LC-MS, ESI+), RT=1.85 (M+H 441.3).
Reaction SMILES: [CH2:1]([O:3][NH:4][C:5](=[O:8])[CH2:6][Cl:7])[CH3:2].[CH:9]([N:12]=[C:13]=[O:14])([CH3:11])[CH3:10]>C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC.C1C=CC=CC=1>[Cl:7][CH2:6][C:5]([O:8][C:13](=[O:14])[NH:12][CH:9]([CH3:11])[CH3:10])=[N:4][O:3][CH2:1][CH3:2]
Reactant: CC(C)N=C=O
Reactant: CCONC(=O)CCl
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Solvent: c1ccccc1
Product: CCON=C(CCl)OC(=O)NC(C)C
Temperature: 25 °C

Procedure:
N-Ethoxychloroacetamide (6.9 grams; 0.05 mole), benzene (70 ml) and dibutyltin dilaurate (1 drop) are charged into a glass reaction flask equipped with a mechanical stirrer, thermometer and reflux condenser. Isopropylisocyanate (5.1 grams; 0.06 mole) dissolved in benzene (20 ml) is incrementally added to the reaction mixture, with stirring, at room temperature. After the addition is completed the reaction mixture is heated at reflux for a period of about 2 hours. After this time the reaction mixture is distilled to remove benzene and unreacted starting material thereby yielding the desired product 1-chloro-2-(N-isopropylcarbamoyloxy)-2-ethoxyiminoethane.
Reaction SMILES: C([O:3][C:4](=[O:31])[CH2:5][S:6][C:7]1[S:11][C:10]([NH:12][C:13]([N:15]([CH2:24][CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=2)=[O:14])=[N:9][CH:8]=1)C.C1(CN(C2C=CC(S(C)(=O)=O)=CC=2)C(=O)NC2SC=C(CC(O)=O)N=2)CCCC1.C1(CCNC2C=CC(F)=C(F)C=2)CCCC1.C(OC(=O)CSC1SC(N)=NC=1)C>>[CH:26]1([CH2:25][CH2:24][N:15]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=2)[C:13](=[O:14])[NH:12][C:10]2[S:11][C:7]([S:6][CH2:5][C:4]([OH:31])=[O:3])=[CH:8][N:9]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: CCOC(=O)CSc1cnc(NC(=O)N(CCC2CCCC2)c2ccc(F)c(F)c2)s1
Agent: CCOC(=O)CSc1cnc(N)s1
Agent: CS(=O)(=O)c1ccc(N(CC2CCCC2)C(=O)Nc2nc(CC(=O)O)cs2)cc1
Agent: Fc1ccc(NCCC2CCCC2)cc1F
Product: O=C(O)CSc1cnc(NC(=O)N(CCC2CCCC2)c2ccc(F)c(F)c2)s1

Procedure:
The title compound was prepared via {2-[3-cyclopentylethyl-3-(3,4-difluoro-phenyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid ethyl ester in a similar manner as described for the synthesis of {2-[3-cyclopentylmethyl-3-(4-methanesulfonyl-phenyl)-ureido]-thiazol-4-yl}-acetic acid, using cyclopentylethyl-(3,4-difluorophenyl)-amine and (2-amino-thiazol-5-ylsulfanyl)acetic acid ethyl ester
Reaction SMILES: [CH2:1]([Sn](CCCC)(CCCC)CCCC)[CH:2]=[CH2:3].N#N.[Si:19]([O:26][CH2:27][CH:28]1[CH2:42][C:41]2[C:30](=[CH:31][C:32]3[N+:37]([O-:38])=[N:36][C:35](I)=[N:34][C:33]=3[CH:40]=2)[CH2:29]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:3]([C:35]1[N:36]=[N+:37]([O-:38])[C:32]2[CH:31]=[C:30]3[C:41]([CH2:42][CH:28]([CH2:27][O:26][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:29]3)=[CH:40][C:33]=2[N:34]=1)[CH:2]=[CH2:1]
Reactant: C=CC[Sn](CCCC)(CCCC)CCCC
Reactant: CC(C)(C)[Si](C)(C)OCC1Cc2cc3nc(I)n[n+]([O-])c3cc2C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: N#N
Solvent: COCCOC
Product: C=CCc1nc2cc3c(cc2[n+]([O-])n1)CC(CO[Si](C)(C)C(C)(C)C)C3
Yield: 99.1 %

Procedure:
Allyltributyltin (4.35 mL, 14.1 mmol) and Pd(PPh3)4 (0.72 g, 0.64 mmol) were added to a N2-purged, stirred solution of iodide 133 (5.88 g, 12.9 mmol) in DME (80 mL) at 20° C. and the reaction mixture was stirred at reflux temperature under N2 for 8 h. The reaction mixture was cooled and partitioned between EtOAc and brine. The organic layer was separated, dried, and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-5%) of EtOAc/pet. ether, to give alkene 137 (4.75 g, 99%) as a yellow solid: mp (EtOAc/pet. ether) 49-52° C.; 1H NMR δ 8.23 (s, 1H, H-9), 7.74 (s, 1H, H-5), 6.17-6.24 (m, 1H, CH), 5.20-5.34 (m, 2H, CH2), 3.75-3.80 (m, 2H, CH2), 3.59-3.67 (m, 2H, CH2O), 3.13-3.25 (m, 2H, CH2), 2.92-3.04 (m, 2H, CH2), 2.72-2.84 (m, 1H, H-7), 0.87 [s, 9H, SiC(CH3)3], 0.04 [s, 6H, Si(CH3)2]; 13C NMR δ 164.1, 154.1, 148.3, 147.6, 133.0, 132.4, 123.0, 118.2, 114.5, 65.4, 42.0, 41.7, 35.8, 35.5, 25.8 (3), 18.3, −5.41 (2); HRMS (FAB+) calcd for C20H30N3O2Si (MH+) m/z 372.2107, found 372.2110. Anal. calcd for C20H29N3O2Si.¼H2O: C, 63.9; H, 7.9; N, 11.2. Found: C, 63.9; H, 7.7; N, 10.8%.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]#[N:12])=[C:6]([F:13])[CH:5]=1.Br[CH2:15][CH2:16]Br>CN(C=O)C.C1COCC1.CCOC(C)=O>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:11]#[N:12])[CH2:16][CH2:15]2)=[C:6]([F:13])[CH:5]=1
Reactant: BrCCBr
Reactant: N#CCc1ccc(Br)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: N#CC1(c2ccc(Br)cc2F)CC1

Procedure:
To a slurry of sodium hydride (60% dispersion in mineral oil, 0.82 g, 20.6 mmol) in DMF (20 mL) cooled to 0° C. was added a solution of (4-bromo-2-fluoro-phenyl)-acetonitrile (2.0 g, 9.35 mmol) from Step 1 above dissolved in THF (10 mL). The reaction was stirred till gas evolution ceased, and then 1,2-dibromoethane (1.8 mL, 20.6 mmol) was added slowly. The reaction was stirred for 30 minutes, and then diluted with 100 mL EtOAc. The solids were removed by filtration, and the organic layer was washed with 100 mL water. The organic layer was dried over MgSO4, and then filtered. The mother liquor was concentrated by rotary evaporation, and the product was distilled under high vacuum (0.3 torr, 45° C.). Yield: 0.98 g, 44%. 1H NMR (CDCl3) δ: 1.15 (dd, J1=5.31 Hz, J2=2.27 Hz, 2H), 1.48 (dd, J1=5.05 Hz, J2=2.53 Hz, 2H), 6.97-7.12 (m, 3H).
Reaction SMILES: O.[C:2]1([C:8]([CH:10]=[O:11])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1>ClC(Cl)C.[Ti](Cl)(Cl)(Cl)Cl>[O:13]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[CH:10]([OH:11])[C:8](=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:12]
Reactant: O=CC(=O)c1ccccc1
Reactant: COc1ccc(OC)cc1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: CC(Cl)Cl
Solvent: O
Product: COc1ccc(OC)c(C(O)C(=O)c2ccccc2)c1

Procedure:
Phenylglyoxal monohydrate (152 mg, 1 mM) and p-dimethoxybenzene (0.21 ml, 1.5 mM) were dissolved in dichloroethane (2 ml), titanium tetrachloride (0.33 ml, 3 mM) was added, and reacted at room temperature for 4 hours. Using the same procedure as in Example 1, 2',5'-dimethoxylbenzoin was obtained as an oil (219.4 mg, 79.2% yield).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7](/[CH:10]=[CH:11]/[C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[O:13])=[CH:6][CH:5]=1.[H][H]>CO.[Pt](=O)=O>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[O:13])=[CH:6][CH:5]=1
Reactant: COC(=O)c1ccc(/C=C/C(=O)c2ccc(Cl)cc2Nc2ccccn2)cc1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: CO
Product: COC(=O)c1ccc(CCC(=O)c2ccc(Cl)cc2Nc2ccccn2)cc1
Yield: 100.8 %

Procedure:
A mixture of 4-{(E)-3-[4-chloro-2-(pyridin-2-ylamino)-phenyl]-3-oxo-propenyl}-benzoic acid methyl ester (287 mg, 731 μmol) in methanol (12.2 mL) at 25° C. was treated with platinum (IV) oxide (8.3 mg, 36.5 μmol). The reaction was stirred under a balloon of hydrogen gas at 25° C. for 18 h. At this time, the reaction was filtered through a pad of Celite® to remove the catalyst. The Celite® was rinsed with a 10% solution of methanol/methylene chloride (2×30 mL). The filtrate was concentrated in vacuo to afford 4-{3-[4-chloro-2-(pyridin-2-ylamino)-phenyl]-3-oxo-propyl}-benzoic acid methyl ester (291 mg, quant.) as a dark green solid. The material was used without further purification.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][CH2:11][OH:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].OI1(=O)C2C=CC=CC=2C(=O)O1>O1CCCC1>[N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][CH:11]=[O:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc(CCO)c1
Agent: O=C1OI(=O)(O)c2ccccc21
Solvent: C1CCOC1
Product: O=CCc1cccc([N+](=O)[O-])c1

Procedure:
A mixture of 10 g of 2-(3-nitrophenyl)ethanol, 25.1 g of 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide and 300 ml of tetrahydrofuran is heated at reflux for 6 hours. After filtration and concentration of the solvent, the product is used as it is in the following Step.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:17]=3[NH:16][C:15]2=[O:24])[CH2:10][CH2:9]1)=O)(C)(C)C.O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:23][C:21]1[CH:20]=[CH:19][C:18]2[N:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[C:15](=[O:24])[NH:16][C:17]=2[CH:22]=1
Reactant: CC(C)(C)OC(=O)N1CCC(n2c(=O)[nH]c3cc(Cl)ccc32)CC1
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: O=c1[nH]c2cc(Cl)ccc2n1C1CCNCC1
Yield: 89.6 %

Procedure:
A solution of 4-(5-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (1.50 g, 4.3 mmol) and H2O/TFA 5% (15 mL) in CH2Cl2 (20 ml) was stirred at room temperature for 1 h, after which the solvent was removed in vacuo. The residue was purified by gradient flash chromatography on silica gel (CH2Cl2 to EtOH), yielding an off-white/pinkish solid (0.97 g, 90%).
Reaction SMILES: C(OC([N:11]1[CH2:15][CH:14]([C:16]([CH3:18])=[CH2:17])[C@H:13]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:12]1)=O)C1C=CC=CC=1.[H][H]>[C].[Pd].CO>[C:23]([O:22][C:20]([NH:19][C@H:13]1[CH:14]([CH:16]([CH3:18])[CH3:17])[CH2:15][NH:11][CH2:12]1)=[O:21])([CH3:26])([CH3:25])[CH3:24]
Reactant: [H][H]
Reactant: C=C(C)C1CN(C(=O)OCc2ccccc2)C[C@H]1NC(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: CC(C)C1CNC[C@H]1NC(=O)OC(C)(C)C
Reaction time: 1 h

Procedure:
A 10% palladium carbon catalyst (300 mg) was added to a solution of (3S)-1-benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-isopropenylpyrrolidine (300 mg, 832 μmol) in methanol (10 mL), and the resultant mixture was stirred in a hydrogen atmosphere under an ordinary pressure for 2 hours. After filtration, a 10% palladium carbon catalyst (300 mg) was added again to the filtrate, followed by stirring in a hydrogen atmosphere under an ordinary pressure for 1 hour. After filtration, the filtrate was concentrated under reduced pressure, to thereby yield (3S)-3-(tert-butoxycarbonyl)amino-4-isopropylpyrrolidine as a colorless amorphous (172 mg, quantitative amount).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]([CH:10]=1)=[N:7][O:8][N:9]=2.C(O[C:16](=O)[N:17]([C:19]1[CH:24]=[CH:23][C:22](Br)=[C:21]([O:26][CH3:27])[CH:20]=1)C)(C)(C)C>>[N:9]1[O:8][N:7]=[C:6]2[CH:10]=[C:2]([C:22]3[CH:23]=[CH:24][C:19]([NH:17][CH3:16])=[CH:20][C:21]=3[O:26][CH3:27])[CH:3]=[CH:4][C:5]=12
Reactant: COc1cc(N(C)C(=O)OC(C)(C)C)ccc1Br
Reactant: Brc1ccc2nonc2c1
Product: CNc1ccc(-c2ccc3nonc3c2)c(OC)c1

Procedure:
The starting compound is obtained according to the procedure described in Example 7 from 5-bromo-benzo[1,2,5]oxadiazole and (4-bromo-3-methoxy-phenyl)-methyl-carbamic acid tert-butyl ester, as a yellow powder. MS(ES+): 378 (M+23).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:24]2[CH2:29][CH2:28][CH:27](O)[CH2:26][CH2:25]2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[C@@H:14]([CH3:15])[CH2:13][CH2:12][CH:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:10]1(=[O:23])=[O:22].[NH:31]1[CH:35]=[N:34][N:33]=[N:32]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([N:24]2[CH2:29][CH2:28][CH:27]([N:31]3[CH:35]=[N:34][N:33]=[N:32]3)[CH2:26][CH2:25]2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[C@@H:14]([CH3:15])[CH2:13][CH2:12][CH:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:10]1(=[O:23])=[O:22]
Reactant: c1nnn[nH]1
Reactant: C[C@H]1CCC(c2ccccc2)S(=O)(=O)N1Cc1ccc(N2CCC(O)CC2)cc1F
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: C[C@H]1CCC(c2ccccc2)S(=O)(=O)N1Cc1ccc(N2CCC(n3cnnn3)CC2)cc1F
Temperature: 25 °C
Reaction time: 16 h
Yield: 26 %

Procedure:
To a solution of 1-[3-fluoro-4-[[(3S)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2 yl]methyl]phenyl]piperidin-4-ol Stereoisomer A (200 mg, 0.46 mmol, prepared as described in Example 5), tetrazole (36 mg, 0.51 mmol) and triphenylphosphine (135 mg, 0.51 mmol) in dichloromethane (2.5 mL) was added diisopropyl azodicarboxylate (103 mg, 0.51 mmol) dropwise and the reaction was stirred at r.t. for 16 hours. The reaction was partitioned between water and dichloromethane and the organic layer was concentrated and purified by preparative HPLC to give (3S)-2-[[2-fluoro-4-[4-(tetrazol-1-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide Stereoisomer A (57.4 mg, 0.12 mmol, 26% yield) as a white solid. 1H NMR (400 MHz, DMSO) δ 8.99-8.96 (s, 1H), 7.49-7.43 (m, 2H), 7.43-7.29 (m, 4H), 6.89-6.82 (m, 1H), 6.82-6.75 (m, 1H), 5.18-5.07 (m, 1H), 4.50-4.36 (m, 2H), 4.33-4.25 (m, 1H), 4.16-4.03 (m, 1H), 3.87-3.76 (m, 2H), 3.10-2.98 (m, 2H), 2.47-2.37 (m, 1H), 2.31-2.23 (m, 2H), 2.19-2.04 (m, 3H), 1.89-1.73 (m, 1H), 1.70-1.59 (m, 1H), 1.13-1.06 (d, J=6.8 Hz, 3H); LCMS [M+1]+=485.2.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][C:3]=1[CH:4]=O.C([BH3-])#[N:29].[Na+]>CO.C([O-])(=O)C.[NH4+]>[Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][Si:11]([C:24]([CH3:25])([CH3:26])[CH3:27])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:6][C:3]=1[CH2:4][NH2:29]
Reactant: CC(C)(C)[Si](Oc1ccc(Br)c(C=O)c1)(c1ccccc1)c1ccccc1
Reactant: [BH3-]C#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)[Si](Oc1ccc(Br)c(CN)c1)(c1ccccc1)c1ccccc1
Temperature: 25 °C

Procedure:
The product from Step A is dissolved in methanol saturated with ammonium acetate. Sodium cyanoborohydride is added in portions at 0° C., and the reaction stirred at room temperature until complete. The reaction is quenched by the addition of saturated aqueous ammonium chloride and stirred until hydrogen evolution ceases. The resulting suspension is concentrated in vacuo and then partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The layers are separated and the aqueous layer is extracted with methylene chloride. The combined organic layers are dried over sodium sulfate, filtered, and concentrated in vacuo to provide the title product.
Reaction SMILES: C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH:20]([CH3:22])[CH3:21])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:23]([C:30]2[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=2)=[CH:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)(=O)=O)C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[CH:25]1([CH:24]=[C:23]([C:11]2[NH:10][C:14]3=[N:15][CH:16]=[C:17]([O:19][CH:20]([CH3:21])[CH3:22])[CH:18]=[C:13]3[CH:12]=2)[C:30]2[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1
Reactant: CC(C)Oc1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(S(C)(=O)=O)cc1)n2S(=O)(=O)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)Oc1cnc2[nH]c(C(=CC3CCCC3)c3ccc(S(C)(=O)=O)cc3)cc2c1
Yield: 101.1 %

Procedure:
A solution of 1-benzenesulfonyl-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-isopropoxy-1H-pyrrolo[2,3-b]pyridine (310 mg, 0.55 mmol) in tetrahydrofuran (0.5 mL) and a tetrabutylammonium fluoride solution in tetrahydrofuran (1 M, 4 mL, 4 mmol) was stirred at room temperature for 12 h. The reaction mixture was then diluted with ethyl acetate (150 mL), and washed with a saturated aqueous ammonium chloride solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-isopropoxy-1H-pyrrolo[2,3-b]pyridine (236 mg, quant.) as a white solid: LC/MS m/e calcd for C24H28N2O3S [M+H]+ 425.57, observed 425.2.
Reaction SMILES: CON(C)[C:4]([C:6]1[C:11]([N:12]([S:16]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=2)(=[O:18])=[O:17])COC)=[CH:10][C:9]([Cl:30])=[CH:8][N:7]=1)=[O:5].I[C:33]1[C:34]2[CH:41]=[CH:40][N:39]([CH3:42])[C:35]=2[N:36]=[CH:37][N:38]=1.C(O)C.Cl>C1COCC1.C([Mg]Cl)(C)C>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]([S:16]([NH:12][C:11]2[C:6]([C:4]([C:33]3[C:34]4[CH:41]=[CH:40][N:39]([CH3:42])[C:35]=4[N:36]=[CH:37][N:38]=3)=[O:5])=[N:7][CH:8]=[C:9]([Cl:30])[CH:10]=2)(=[O:18])=[O:17])=[CH:20][C:21]=1[C:26]([F:27])([F:29])[F:28]
Reactant: COCN(c1cc(Cl)cnc1C(=O)N(C)OC)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: Cn1ccc2c(I)ncnc21
Agent: CC(C)[Mg]Cl
Agent: Cl
Solvent: C1CCOC1
Solvent: CCO
Product: Cn1ccc2c(C(=O)c3ncc(Cl)cc3NS(=O)(=O)c3ccc(Cl)c(C(F)(F)F)c3)ncnc21

Procedure:
Prepared from 227 mg (0.45 mmol) of 5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid methoxy-methyl-amide, 129 mg (0.45 mmol) of 90% 4-iodo-7-methyl-7H-pyrrolo[2,3-d]pyrimidine dissolved in 2 mL THF with 0.23 mL of 2 M isopropylmagnesium chloride solution in THF added. All of the resulting intermediate ketone (80 mg) was used in the second step with 2 mL ethanol and 2 mL 6N hydrochloric acid mixture to give after purification 45 mg of the final product as a yellow solid.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].Cl[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[N:15]=1>>[NH2:20][C:16]1[N:17]=[C:18]([NH:1][CH2:2][CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:9])[CH3:10])[CH:19]=[CH:14][N:15]=1
Reactant: CN(CCN)C(=O)OC(C)(C)C
Reactant: Nc1nccc(Cl)n1
Product: CN(CCNc1ccnc(N)n1)C(=O)OC(C)(C)C

Procedure:
tert-Butyl 2-aminoethyl(methyl)carbamate (337 mg, 1.93 mmol) and 4-chloropyrimidin-2-amine (260 mg, 2.01 mmol) were combined under the conditions described in Example 1D to afford tert-butyl 2-[(2-aminopyrimidin-4-yl)amino]ethyl(methyl)carbamate. MS (M+H)+ m/z 268.3. The intermediate was treated under the conditions of Example 1E to afford the title compound. MS (ESI+) m/z 167.9 (M+H)+.
Reaction SMILES: O1C2=CN=CC=C2C(=O)C1.C(OC([C:16]1[O:26][C:19]2=[N:20][CH:21]=[CH:22][C:23]([O:24][CH3:25])=[C:18]2[C:17]=1[OH:27])=O)C>>[CH3:25][O:24][C:23]1[CH:22]=[CH:21][N:20]=[C:19]2[O:26][CH2:16][C:17](=[O:27])[C:18]=12
Reactant: CCOC(=O)c1oc2nccc(OC)c2c1O
Agent: O=C1COc2cnccc21
Product: COc1ccnc2c1C(=O)CO2

Procedure:
This compound was prepared using a method analogous to that of furo[2,3-c]pyridin-3(2H)-one (A.2.4.3), 3-hydroxy-4-methoxyfuro[2,3-b]pyridine-2-carboxylic acid ethyl ester replacing 3-hydroxyfuro[2,3-c]pyridine-2-carboxylic acid ethyl ester;