Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[CH:8]=[CH:7][C:5]=2[N:6]=1.[NH:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[CH2:26][C@H:15]12.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>>[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]([N:14]3[CH2:19][CH2:18][CH2:17][C@@H:16]4[C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=5[CH2:26][C@H:15]34)=[O:13])[CH:8]=[CH:7][C:5]=2[N:6]=1
Reactant: Nc1nc2ccc(C(=O)O)cc2s1
Reactant: c1ccc2c(c1)C[C@@H]1NCCC[C@H]21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: Nc1nc2ccc(C(=O)N3CCC[C@@H]4c5ccccc5C[C@@H]43)cc2s1
Yield: 63 %

Procedure:
The title compound is prepared from 2-amino-benzothiazole-6-carboxylic acid and cis-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine following a procedure analogous to that described in Example 1 [2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexa-fluorophosphate is used]. Yield: 63% of theory; LC (method 4): tR=1.76 min; Mass spectrum (ESI+): m/z=350 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)[S:5][C:6]=1[C:7](=[O:15])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=1.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[NH2:1][C:2]1[N:3]=[C:4]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([N:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)=[CH:21][CH:22]=2)[S:5][C:6]=1[C:7]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=1)=[O:15]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(Nc3nc(N)c(C(=O)c4cccc(F)c4)s3)cc2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1nc(Nc2ccc(N3CCNCC3)cc2)sc1C(=O)c1cccc(F)c1
Reaction time: 8 h
Yield: 100.6 %

Procedure:
A mixture of 4-[4-[[4-amino-5-(3-fluorobenzoyl)-2-thiazolyl]amino]phenyl]-1-piperazinecarboxylic acid, 1,1-dimethylethyl ester (75 mg, 0.15 mmol) (from Step A above) and a solution of TFA/CH2Cl2 (1:1; 1.5 mL) was gently shaken for 1.5 h. The solution was evaporated in vacuo. To the residue was added resin-bound N,N-diisopropylethylamine (2.5 g, loading capacity: 3.8 mmol/g from Argonaut, Inc.) and CH2Cl2 (15 mL). After shaking overnight, the mixture was filtered and washed successively with CH3OH and CH2Cl2. The solvent was evaporated in vacuo and the residue was triturated by diethyl ether/hexanes (1/9) to afford [4-amino-2-[[4-(1-piperazinyl)phenyl]amino]-5-thiazolyl](3-fluorophenyl)methanone (60 mg, 100%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH:16]=O)[CH:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:20][OH:21]>C(O)C>[C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH:16]=[N:20][OH:21])[CH:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]
Reactant: NO
Reactant: C[C@H](NC(=O)OC(C)(C)C)c1cccc(C=O)c1
Agent: Cl
Solvent: CCO
Product: C[C@H](NC(=O)OC(C)(C)C)c1cccc(C=NO)c1
Temperature: 25 °C
Yield: 96.5 %

Procedure:
To a solution of (s)-[1-(3-formyl-phenyl)-ethyl]-carbamic acid tert-butyl ester (1.5 g, 6 mmol) in ethanol (50 mL) were added hydroxylamine hydrochloride (833 mg, 12 mmol) triethylamine (2.5 mL, 18 mmol), the reaction mixture was heated at reflux for 18 h, and the reaction mixture was cooled down to room temperature and concentrated in vacuo. The crude product was diluted in EtOAc (100 mL) and extracted with 0.5N HCl. The organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated in vacuo to provide the title compound (1.53 g, 96% yield) as a solid.
Reaction SMILES: F[C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[C:4]([N+:15]([O-])=O)[C:3]=1[NH2:18]>O=[Mn]=O.CCOC(C)=O>[CH:14]1([N:11]2[CH2:12][CH2:13][N:8]([C:7]3[CH:2]=[C:3]([NH2:18])[C:4]([NH2:15])=[CH:5][CH:6]=3)[CH2:9][CH2:10]2)[CH2:4][CH2:3][CH2:2][CH2:7]1
Reactant: CN1CCN(c2ccc([N+](=O)[O-])c(N)c2F)CC1
Agent: O=[Mn]=O
Solvent: CCOC(C)=O
Product: Nc1ccc(N2CCN(C3CCCC3)CC2)cc1N
Temperature: 120 °C
Reaction time: 2 h
Yield: 188.9 %

Procedure:
A 250 mL reaction tube was charged with benzyl alcohol 1 (1.0 g, 3.6 mmol), MnO2 (4.7 g, 54 mmol) and EtOAc (20 mL). The reaction tube was sealed was heated to 120° C. with stirring for 2 h. The reaction was allowed to cool to rt, then filtered through Celite and washed successively with EtOAc, MeOH, and EtOH. The combine organics were concentrated to give 936 mg (3.4 mmol, 94%) of 2 as an orange solid: 1H NMR (300 MHz, CDCl3) δ 10.01 (s, 1H), 8.64 (d, J=5.5 Hz, 1H), 8.09 (br s, 1H), 7.96 (d, J=2.75 Hz, 1H), 7.37 (d, J=2.48 Hz, 1H), 7.29 (d, J=2.75 Hz, 1H), 7.08 (dd, J=2.47, 5.5 Hz, 1H), 6.94 (d, J=9.35 Hz, 1H), 3.08 (d, J=5.23 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]([OH:13])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:14]([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C([O-])[O-]
Reactant: O=C(O)C=Cc1ccc(Cl)c(Cl)c1
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COC(=O)C=Cc1ccc(Cl)c(Cl)c1
Reaction time: 0.25 h
Yield: 148.5 %

Procedure:
Cool a solution of 3-(3,4-dichlorophenyl)-2-propeneoic acid (100 g, 461 mmol) in dry DMF (500 mL) to 0° C. and treat with Cs2CO3 (100 g, 307 mmol, 0.66 eq). Stir the resulting off-white slurry for 15 min, then add CH3 l (33 mL, 530 mmol, 1.15 eq) via syringe. After 1 h, add additional DMF (250 mL), stir the slurry for 14 h and partition between EtOAc (1.5 L) and half saturated aqueous NaHCO3 (500 mL). Separate the organic layer and extract the aqueous layer twice with EtOAc (1 L, 500 mL). Wash the combined organic layers with half saturated aqueous NaHCO3 (500 mL) and water (5×500 mL), then dry (Na2SO4) and concentrate to obtain 105.4 g (456 mmol, 99%) of methyl 3-(3,4-dichlorophenyl)-2-propenoate as light brown needles.
Reaction SMILES: [C:1]([N:9]1[CH2:14][CH2:13][CH:12]([C:15]([O:17]C)=O)[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[NH2:20][NH2:21].O>CO>[C:1]([N:9]1[CH2:14][CH2:13][CH:12]([C:15]([NH:20][NH2:21])=[O:17])[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NN
Reactant: COC(=O)C1CCN(C(=O)c2ccccc2)CC1
Solvent: CO
Solvent: O
Product: NNC(=O)C1CCN(C(=O)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a suspension of (±)-methyl 1-benzoyl-4-piperidinecarboxylate (502 mg, 2.03 mmol) in MeOH (10 mL) was added hydrazine hydrate (1.6 mL). After stirring for 24 h at rt, the reaction mixture and water (40 mL) was added. After washing with Et2O (2×20 mL), the aqueous layer was evaporated off under vacuo. The title compound was obtained as an amorphous beige solid (469 mg, 93%) in a 91.0% purity by HPLC (MaxPlot detection between 230 and 400 nm).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][CH2:18][CH2:19][CH3:20])=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[CH2:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)=[O:15])[CH2:18][CH2:19][CH3:20]
Reactant: CCCCOC(=O)N1CCN(C(=O)OC(C)(C)C)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCCOC(=O)N1CCNCC1
Reaction time: 12 h

Procedure:
To a solution of 18.0 g piperazine-1,4-dicarboxylic acid butyl ester tert-butyl ester in 70 ml dichloromethane were added 23 ml TFA. After stirring for 12 h the solution was concentrated and the residue codistilled with toluene twice. Yield: 18.5 g.
Reaction SMILES: Cl.Cl.[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]2)[CH:5]=1.Cl[C:18]1[N:23]=[C:22]([C:24]([OH:27])([CH3:26])[CH3:25])[CH:21]=[C:20]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[N:19]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O.O>[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([NH:16][C:18]3[N:23]=[C:22]([C:24]([OH:27])([CH3:26])[CH3:25])[CH:21]=[C:20]([C:28]4[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:30][CH:29]=4)[N:19]=3)[CH2:12][CH2:11]2)[CH:5]=1
Reactant: Cc1cc(N2CCC(N)CC2)ncn1
Reactant: CC(C)(O)c1cc(-c2ccc(C(F)(F)F)cc2)nc(Cl)n1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CN1CCCC1=O
Product: Cc1cc(N2CCC(Nc3nc(-c4ccc(C(F)(F)F)cc4)cc(C(C)(C)O)n3)CC2)ncn1

Procedure:
A solution of 1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamine dihydrochloride (53 mg, 0.2 mmol), 2-[2-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yl]-propan-2-ol (69.7 mg, 0.22 mmol)) and N,N-diisopropylethyl amine (120 L, 0.7 mmol) in N-methyl-pyrrolidinone (1 mL) was heated at 160° C. in a microwave oven for 5 hours. The reaction was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a gradient from AcOEt to AcOEt/EtOH 9:1 (v/v) as eluent. The title compound was obtained as a white solid (36 mg, 38%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH2:11](Cl)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>O>[CH2:11]([NH:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: NC(=O)c1ccccc1N
Reactant: ClCc1ccccc1
Solvent: O
Product: NC(=O)c1ccccc1NCc1ccccc1

Procedure:
To a hot solution of 20 g Na OHin 1250 ml water was added 68 g 2-aminobenzamide followed by 58 ml benzyl chloride. The mixture was refluxed 20 minutes, cooled and the solid filtered and washed with water. The product was recrystallized from 95% alcohol to give 62 g, m.169-73°.
Reaction SMILES: Cl.[OH:2][NH2:3].C(N(CC)CC)C.[O:11]1[C:15]2[CH:16]=[CH:17][C:18]([C:20]3[C:21]4[C:35](=[O:36])[O:34][C:33](=O)[C:22]=4[CH:23]=[C:24]4[C:32]=3[C:28]3[O:29][CH2:30][O:31][C:27]=3[CH:26]=[CH:25]4)=[CH:19][C:14]=2[O:13][CH2:12]1>CCO>[O:11]1[C:15]2[CH:16]=[CH:17][C:18]([C:20]3[C:32]4[C:24](=[CH:25][CH:26]=[C:27]5[O:31][CH2:30][O:29][C:28]5=4)[CH:23]=[C:22]4[C:33](=[O:34])[N:3]([OH:2])[C:35](=[O:36])[C:21]=34)=[CH:19][C:14]=2[O:13][CH2:12]1
Reactant: NO
Reactant: O=C1OC(=O)c2c1cc1ccc3c(c1c2-c1ccc2c(c1)OCO2)OCO3
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=C1c2cc3ccc4c(c3c(-c3ccc5c(c3)OCO5)c2C(=O)N1O)OCO4
Reaction time: 0.17 h
Yield: 14.1 %

Procedure:
Hydroxyamine hydrochloride (20.9 mg, 0.3 mmol) and triethylamine (0.04 mL, 0.3 mmol) were dissolved in EtOH (30 mL). After stirring for 10 min, anhydride 1 (109 mg, 0.3 mmol) was added. The mixture was refluxed overnight and then concentrated in vacuo. The resulting product was purified by silica gel column chromatography using CH2Cl2/acetone (2:1, v/v) to afford 24 (16 mg, 15%) as a yellow powder. mp 255° C. (decomp.); 1H NMR (DMSO-d6) δ 10.78 (s, 1H, OH), 8.40 (s, 1H, H4), 7.89 (d, 1H, H5, J=8.7 Hz), 7.54 (d, 1H, H6, J=8.7 Hz), 6.94 (s, 1H, H2′), 6.90 (d, 1H, H5′, J=7.8 Hz), 6.79 (d, 1H, H6′, J=7.8 Hz), 6.08 (s, 2H, 3′,4′-OCH2O—), 5.96 (AB, 2H, 7,8-OCH2O—, Δδ=5.7 Hz); MS (FAB, positive) m/z 378 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([OH:6])=O.[C:12]1([CH:18]([C:21]2[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=2)[CH2:19][NH2:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[Cl:11][C:7]1[CH:8]=[CH:9][CH:10]=[CH:2][C:3]=1[C:4]([NH:20][CH2:19][CH:18]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:21]1[CH:22]=[N:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=1)=[O:6]
Reactant: O=C(O)c1c(Cl)cccc1Cl
Reactant: NCC(c1ccccc1)c1ccc(C(F)(F)F)nc1
Product: O=C(NCC(c1ccccc1)c1ccc(C(F)(F)F)nc1)c1ccccc1Cl

Procedure:
The racemic mixture which was prepared in a similar manner to example 3a from 2,6-dichlorobenzoic acid and 2-phenyl-2-(6-(trifluoromethyl)pyridin-3-yl)ethanamine was separated into the two enantiomers by preparative SFC to yield the title compound. LCMS (MH+): m/z=439.1, tR (minutes, Method G)=2.76. [α]D20=+3.18 (c=6.38 mg/mL,CHCl3)
Reaction SMILES: [F:1][C:2]1[C:7](I)=[CH:6][CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:17]2[CH2:18][CH2:19][CH2:20][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:22]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O.C(OCC)(=O)C.C(O)C>[F:1][C:2]1[C:7]([C:19]2[CH2:18][CH2:17][CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:20]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: CC(C)(C)OC(=O)N1C=C(B2OC(C)(C)C(C)(C)O2)CCC1
Reactant: Fc1ncccc1I
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: COCCOC
Product: CC(C)(C)OC(=O)N1C=C(c2cccnc2F)CCC1
Temperature: 140 °C

Procedure:
A microwave vial was charged with 2-fluoro-3-iodopyridine (1.325 g, 5.94 mmol), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate (1.8 g, 5.82 mmol), sodium carbonate hydrate (2166 mg, 17.46 mmol), catalyst (211 mg, 0.301 mmol), DME (3 mL), Ethanol (0.857 mL) and Water (1.286 mL). The vial was capped and heated in a Biotage Initiator to 140° C. for 15 minutes. The reaction was diluted with water (20 ml) and ethyl acetate (30 ml). The organic layer was washed with water (2×10 mL), brine (10 mL), and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with 0% to 50% EtOAc in hexane, to provide tert-butyl 5-(2-fluoropyridin-3-yl)-3,4-dihydropyridine-1(2H)-carboxylate as a colorless syrup. MS (ESI, pos. ion) m/z: 332.1 (M+Na).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:26](O)=[O:27])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][C@H:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][CH2:18]3)=[O:15])[CH:9]=2)=[CH:6][N:7]=1.[NH:29]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]([NH2:36])[CH2:30]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>>[NH2:1][C:2]1[C:3]([C:26]([NH:36][CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35][NH:29][CH2:30]2)=[O:27])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][C@@H:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][CH2:18]3)=[O:15])[CH:9]=2)=[CH:6][N:7]=1
Reactant: NC1CCCCNC1
Reactant: Nc1ncc(-c2cccc(C(=O)N[C@@H]3CCc4ccccc43)c2)nc1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Product: Nc1ncc(-c2cccc(C(=O)N[C@H]3CCc4ccccc43)c2)nc1C(=O)NC1CCCCNC1
Reaction time: 2 h
Yield: 4.3 %

Procedure:
To a solution of 3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxylic acid (409 mg, 1.09 mmol) were added azepan-3-amine (125 mg, 1.09 mmol), EDCI (252 mg, 1.31 mmol), HOBt (178 mg, 1.31 mmol) at ambient temperature. After being stirred for 2 h, the reaction mixture was quenched by addition of aqueous sodium bicarbonate followed by extraction with ethyl acetate (20 mL×3). The aqueous phase was extracted once with additional ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride then dried over anhydrous magnesium sulfate. Filtration and concentration in vacuo gave a crude oil, which was purified by preparative HPLC to yield the 3-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide (22 mg, 4.2% yield): 1H NMR (400 MHz, CD3OD): δ 8.70 (m, 1H), 8.67 (m, 1H), 8.27 (m, 1H) 7.97 (m, 1H), 7.62 (t, 1H), 7.25 (m, 4H), 5.70 (m, 1H), 4.99 (m, 1H), 4.43 (m, 1H), 3.46 (m, 2H), 3.38 (m, 1H), 3.15 (m, 2H), 2.94 (m, 1H), 2.61 (m, 1H), 2.17 (m, 2H), 1.95 (m, 4H), 1.62 (m, 1H); MS (EI) for C27H30N6O2: 471.32 (MH+).
Reaction SMILES: [C:1](O)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]C.C(OC(=O)CC)(=O)CC.CP(C)C1C=CC=CC=1>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[ClH+][Rh-][ClH+].[Rh]>[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Agent: [ClH+][Rh-][ClH+]
Agent: [Rh]
Agent: CCC(=O)OC(=O)CC
Product: C=CCCCCCCCCCCCCCCC
Temperature: 255 °C
Yield: 639.3 %

Procedure:
In a procedure similar to example 3, a mixture of stearic acid (70.0 g, 0.246 mol), propionic anhydride (16.0 g, 0.123 mol), chlorodicarbonylrhodium (I) dimer (0.48 g, 0.0012 mol), and dimethylphenylphosphine (0.68 g, 0.0049 mol) was heated under reduced pressure (35-45 torr) using an oil bath maintained at 255° C. and the product collected as it distilled from the reactor. The material removed from the reactor was continuously replaced with a mixture of stearic acid and propionic anhydride (4:3 molar mixture, respectively) in a rate that maintained the initial level of the reactor contents throughout the course of the entire reaction. The formation of product ceased after ca. 8 hours of reaction time. The combined distillate product was washed with water and distilled to provide 375 g of 1-heptadecene (bp 140° C./0.6 torr) which was found by GC analysis to be 93.4% of the α-olefin. TON=657.
Reaction SMILES: [CH3:1][C:2]1[C:3]2[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=2[S:5][C:6]=1[SH:7].S1C(S)=CC2C=CC=CC1=2.[S].Cl[CH2:24][C:25]([N:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][CH2:28]1)=[O:26].S1C(SCC(N2C3C(=CC=CC=3)CCC2)=O)=CC2C=CC=CC1=2>>[N:27]1([C:25](=[O:26])[CH2:24][S:7][C:6]2[S:5][C:4]3[CH:8]=[CH:9][CH:10]=[CH:11][C:3]=3[C:2]=2[CH3:1])[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][CH2:28]1
Reactant: O=C(CCl)N1CCCc2ccccc21
Reactant: Cc1c(S)sc2ccccc12
Agent: O=C(CSc1cc2ccccc2s1)N1CCCc2ccccc21
Agent: Sc1cc2ccccc2s1
Agent: [S]
Product: Cc1c(SCC(=O)N2CCCc3ccccc32)sc2ccccc12
Yield: 5 %

Procedure:
Compound 75 was obtained according to the procedure used to synthesize compound 72, except the addition of sulfur was done at 40° C. in an attempt to avoid significant formation of disulfide. The obtained crude material (75) was used for the next step without further purification. 1-(3,4-dihydroquinolin-1(2H)-yl)-2-(3-methylbenzo[b]thiophen-2-ylthio)-ethanone (76): Crude compound 75 (0.55 g, 3.0 mmol) was coupled with compound 4 (0.48 g, 2.3 mmol) according to procedure used to synthesize compound 73. The product was purified by column chromatography to yield compound 76 (95 mg, 5% for two steps): MS: m/z+354.1 [M+H]+; Anal. Calcd (found) for C20H19NOS2.0.1H2O: C, 67.61; (67.59), H, 5.45; (5.48), N, 3.94; (3.94), S, 18.05; (17.75).
Reaction SMILES: [ClH:1].[CH3:2][CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([N+:13]([O-])=O)[CH:11]=2)[CH2:6][CH2:5][NH:4]1.[H][H]>C(O)C.[Pd]>[ClH:1].[CH3:2][CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH2:13])[CH:11]=2)[CH2:6][CH2:5][NH:4]1
Reactant: CC1NCCc2ccc([N+](=O)[O-])cc21
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: CC1NCCc2ccc(N)cc21

Procedure:
A suspension of 1-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline hydrochloride (2.0 g, 8.75 mmol) in ethanol (100 ml) and a catalytic quantity of 10% Pd-C was hydrogenated until no more hydrogen was taken up. The catalyst was filtered off, the solvent was concentrated to a small volume, ether was added and the precipitated solid was collected and dried: 1.39 g (78%), MS (M+H)+ 163.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=2[CH3:24])[CH2:13][CH:14]([CH3:16])[CH3:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.[H-].[Na+].[CH3:27][OH:28]>CC1CCCO1>[CH3:24][C:18]1[CH:19]=[C:20]([CH3:23])[CH:21]=[CH:22][C:17]=1[N:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[S:9]([C:6]1[CH:7]=[CH:8][C:3]([CH2:2][O:28][C:27]2[CH:18]=[CH:17][N:12]=[CH:13][CH:14]=2)=[CH:4][CH:5]=1)(=[O:11])=[O:10]
Reactant: Cc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(CBr)cc2)c(C)c1
Reactant: CO
Agent: [H-]
Agent: [Na+]
Solvent: CC1CCCO1
Product: Cc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(COc3ccncc3)cc2)c(C)c1
Temperature: 25 °C
Yield: 10 %

Procedure:
To a solution of an alcohol (1.276 mg, 0.075 mmol, see Table 4 for specific alcohol used for each reaction) and 4-(bromomethyl)-N-(2,4-dimethylphenyl)-N-isobutylbenzenesulfonamide (0.031 g, 0.075 mmol) in 2-Methyltetrahydrofuran (2-MeTHF) (1 mL) stirred under nitrogen at room temperature was added solid sodium hydride (1.800 mg, 0.075 mmol) (tip of spatula). The reaction mixture was stirred at 20° C. for 3 hrs. The reaction was carefully quenched with water (5 drops per reaction). The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus to give the crude product. The sample was dissolved in 1:1 MeOH:DMSO 1 mL and purified by mass directed autoprep on an Xbridge column using acetonitrile:water with an ammonium carbonate modifier. The solvent was dried under a stream of nitrogen in the Radley's blowdown apparatus to give the required product (3.89 mg, 10% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:26][C:11]3=[N:12][CH:13]=[C:14]([NH:16][C:17](=[O:25])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[Cl:24])[CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:27](Cl)(=[O:29])[CH3:28]>N1C=CC=CC=1>[C:27]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:26][C:11]3=[N:12][CH:13]=[C:14]([NH:16][C:17](=[O:25])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[Cl:24])[CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)Cl
Reactant: Nc1cccc(-c2nc3cc(NC(=O)c4ccccc4Cl)cnc3[nH]2)c1
Solvent: c1ccncc1
Product: CC(=O)Nc1cccc(-c2nc3cc(NC(=O)c4ccccc4Cl)cnc3[nH]2)c1

Procedure:
10 mg of the product from example 10-1 were dissolved in 1 ml dry pyridine and 6 μl acetyl chloride were added at room temperature. After stirring over night, the solvent was evaporated and the residue dissolved in 3 ml methanol. 1 ml conc. ammonia were added and the mixture stirred for 1 hr at room temperature. The solvents were again evaporated and the residue purified by chromatography on C-18 RP silica in water methanol mixtures. Yield 7.3 mg
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[CH:7]([C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1)([CH3:9])[CH3:8].Br[C:20]1[C:21]([NH2:26])=[N:22][CH:23]=[CH:24][CH:25]=1.O>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>[CH3:8][CH:7]([C:10]1[CH:15]=[CH:14][C:13]([C:20]2[C:21]([NH2:26])=[N:22][CH:23]=[CH:24][CH:25]=2)=[CH:12][CH:11]=1)[CH3:9]
Reactant: Nc1ncccc1Br
Reactant: CC(C)c1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CC(C)c1ccc(-c2cccnc2N)cc1
Yield: 92.4 %

Procedure:
A mixture of 2M aqueous sodium carbonate solution (8.67 ml), tetrakis(triphenylphosphine)palladium(0) (668 mg), 4-isopropylphenylboronic acid (2844 mg) and 3-bromopyridin-2-amine (2.0 g) in 1,2-dimethoxyethane (30 ml) was heated under reflux overnight. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2267 mg) as a white solid.
Reaction SMILES: C[O:2][C:3](=[O:27])[C@@H:4]([N:12]1[CH2:16][C:15]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[S:24][CH3:25])=[CH:14][C:13]1=[O:26])[CH2:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[Li+]>O1CCCC1.O>[CH:6]1([CH2:5][C@H:4]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[S:24][CH3:25])=[CH:14][C:13]2=[O:26])[C:3]([OH:27])=[O:2])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1
Reactant: COC(=O)[C@H](CC1CCCCC1)N1CC(Oc2ccccc2SC)=CC1=O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CSc1ccccc1OC1=CC(=O)N([C@@H](CC2CCCCC2)C(=O)O)C1
Temperature: 23 °C
Reaction time: 2 h
Yield: 53.3 %

Procedure:
To a stirred solution of (S)-3-cyclohexyl-2-[4-(2-methylsulfanyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid methyl ester (250 mg, 0.001 mol) in tetrahydrofuran-water (3:1, 12 mL) was added lithium hydroxide (0.080 g, 0.003 mol). The reaction mixture was stirred at 23° C. for 2 h. After this time, the mixture was concentrated and the reaction mixture was diluted with water. The reaction mixture was acidified with 2N hydrochloric acid, during which time precipitation occurred. The precipitate was removed by filtration, washed with cold water and dried in vacuo to obtain (S)-3-cyclohexyl-2-[4-(2-methylsulfanyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (200 mg, 83%) as a semi-solid.