Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@@:2]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:6][C:5](=[O:7])[N:4]([C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:3]1.P(OCC)(OCC)[O:24]CC.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCCC1>[OH:24][CH:6]1[C:5](=[O:7])[N:4]([C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:3][C@:2]1([CH3:1])[C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17]
Reactant: CCOP(OCC)OCC
Reactant: C[C@H](c1ccccc1)N1C[C@](C)(C(=O)OC(C)(C)C)CC1=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: C[C@H](c1ccccc1)N1C[C@](C)(C(=O)OC(C)(C)C)C(O)C1=O
Reaction time: 0.5 h
Yield: 74.2 %

Procedure:
To a solution of tert-butyl (3R)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (9.90 g, 32.6 mmol) and tri ethyl phosphite (6.71 mL, 39.1 mmol) in anhydrous tetrahydrofuran (165 mL), lithium bistrimethylsilyl amide (45.7 mL, 45.7 mmol, 1.0M solution in tetrahydrofuran) was added at −5° C., and the mixture was stirred at the same temperature for 30 minutes. After bubbling oxygen gas into the reaction mixture for 30 minutes, saturated aqueous solution of ammonium chloride (150 mL) was added in an ice bath, and the mixture was concentrated under reduced pressure. Water (100 mL) was added to the residue and the mixture was extracted with ethyl acetate (200 mL×2). The organic layer was washed with saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 1:1→1:4) to obtain 7.73 g (74%) of the title compound as a pale yellow oily substance.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:32])[N:17]([CH2:21][C:22]3[N:26]([CH3:27])[C:25]4[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=4[N:23]=3)[CH2:18]C=O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[BH3-][C:34]#[N:35].[Na+].[C:37]([OH:40])(=[O:39])[CH3:38]>CO>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:17]([CH2:21][C:22]3[N:26]([CH3:27])[C:25]4[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=4[N:23]=3)[CH2:18][CH2:34][NH:35][C@@H:38]([C@@H:8]([CH3:7])[CH2:9][CH3:10])[C:37]([O:40][C:5]([CH3:6])([CH3:13])[CH3:4])=[O:39])=[O:32])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: [BH3-]C#N
Reactant: Cn1c(CN(CC=O)C(=O)OCC2c3ccccc3-c3ccccc32)nc2ccccc21
Reactant: CC(=O)O
Agent: [Na+]
Solvent: CO
Product: CC[C@H](C)[C@H](NCCN(Cc1nc2ccccc2n1C)C(=O)OCC1c2ccccc2-c2ccccc21)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of the product of Example 59C (0.81 mmol ) and (L)-methyl iso-leucinate hydrochloride (0.182 g, 0.813 mmol) in methanol (3.2 mL) and acetic acid (0.032 mL) was treated with NaCNBH3 (0.104 g, 1.65 mmol), stirred at 25° C. for 1 hour, and partitioned between water and dichloromethane. The organic phase layer was separated and washed with 1N NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. The crude product was used without further purification.
Reaction SMILES: CO.O1CCCC1.C([O:15][C:16]1[C:21]([C:22]([NH:24][CH3:25])=[O:23])=[CH:20][CH:19]=[C:18]([O:26][CH3:27])[C:17]=1[CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][CH:33]([N:36]2[C:44]3[C:39](=[CH:40][CH:41]=[C:42]([C:45]([NH2:47])=[O:46])[CH:43]=3)[CH:38]=[CH:37]2)[CH2:32][CH2:31]1)C1C=CC=CC=1>[Pd]>[OH:15][C:16]1[C:21]([C:22]([NH:24][CH3:25])=[O:23])=[CH:20][CH:19]=[C:18]([O:26][CH3:27])[C:17]=1[CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][CH:33]([N:36]2[C:44]3[C:39](=[CH:40][CH:41]=[C:42]([C:45]([NH2:47])=[O:46])[CH:43]=3)[CH:38]=[CH:37]2)[CH2:32][CH2:31]1
Reactant: CNC(=O)c1ccc(OC)c(CCN2CCC(n3ccc4ccc(C(N)=O)cc43)CC2)c1OCc1ccccc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: CNC(=O)c1ccc(OC)c(CCN2CCC(n3ccc4ccc(C(N)=O)cc43)CC2)c1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.7 %

Procedure:
15 ml of methanol and 10 ml of tetrahydrofuran were added to and dissolved in 486 mg of 1-(1-(2-(2-(benzyloxy)-6-methoxy-3-((methylamino)carbonyl)phenyl)ethyl)piperidin-4-yl)-1H-indole-6-carboxamide. Thereafter, 74 mg of 10% Pd—C (containing water) was added thereto, and the obtained mixture was then stirred at room temperature under hydrogen atmosphere overnight. Thereafter, Pd—C was removed by filtration, and the solvent was removed under a reduced pressure, so as to obtain 408 mg of the subject compound.
Reaction SMILES: CN1CCCCC1.[CH:8]([O:11][C:12]([NH:14][C@H:15]([C:19]([OH:21])=O)[CH:16]([CH3:18])[CH3:17])=[O:13])([CH3:10])[CH3:9].ClC(OCC(C)C)=O.[F:30][C:31]1[CH:32]=[CH:33][C:34]2[O:38][C:37]([CH:39]([NH2:41])[CH3:40])=[CH:36][C:35]=2[CH:42]=1>ClCCl.O>[F:30][C:31]1[CH:32]=[CH:33][C:34]2[O:38][C:37]([CH:39]([NH:41][C:19](=[O:21])[C@H:15]([CH:16]([CH3:17])[CH3:18])[NH:14][C:12]([O:11][CH:8]([CH3:9])[CH3:10])=[O:13])[CH3:40])=[CH:36][C:35]=2[CH:42]=1
Reactant: CC(N)c1cc2cc(F)ccc2o1
Reactant: CC(C)OC(=O)N[C@H](C(=O)O)C(C)C
Agent: CC(C)COC(=O)Cl
Solvent: O
Solvent: ClCCl
Solvent: CN1CCCCC1
Product: CC(C)OC(=O)N[C@H](C(=O)NC(C)c1cc2cc(F)ccc2o1)C(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 61.3 %

Procedure:
4.7 g of N-methylpiperidine was added to a solution containing 9.7 g of N-isopropoxycarbonyl-L-valine dissolved in 100 ml of dichloromethane, at -20° C. and the mixture was stirred for 15 minutes at the same temperature. Subsequently, 6.5 g of isobutyl chloroformate was added to the mixture at -30° C. and then the whole mixture was stirred between -30° C. and -20° C. for 30 minutes. 8.5 g of 1-(5-fluoro-2-benzofuranyl)ethylamine was then added to the mixture at -50° C. The mixture was allowed to sit and warm naturally to room temperature and then stirred for 15 hours at room temperature. Water was subsequently added to the reaction mixture. After the dichloromethane layer was washed with water, the organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue, which was a crude crystal, was purified by column chromatography on silica gel, thus obtaining 10.6 g of the desired product in the form of a white powder.
Reaction SMILES: [C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].[CH2:6]([C:9]1[O:13][N:12]=[C:11]([C:14](Cl)=[O:15])[CH:10]=1)[CH2:7][CH3:8].O>ClCCl>[C:1]([NH:5][C:14]([C:11]1[CH:10]=[C:9]([CH2:6][CH2:7][CH3:8])[O:13][N:12]=1)=[O:15])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCc1cc(C(=O)Cl)no1
Reactant: CC(C)(C)N
Solvent: O
Solvent: ClCCl
Product: CCCc1cc(C(=O)NC(C)(C)C)no1
Temperature: 25 °C
Reaction time: 12 h
Yield: 94.9 %

Procedure:
At 5° C., 9.3 g (126.8 mmol) of tert-butylamine in 20 ml of dichloromethane was dripped into 10.0 g (57.6 mmol) of 5-n-propyl-isoxazole-3-carboxylic chloride in 250 ml of anhydrous dichloromethane. The mixture was stirred for 12 hours at room temperature, 200 ml of water was added, the phases were separated, the organic phase was washed once with 150 ml of saturated sodium bicarbonate solution and once with 150 ml of saturated sodium chloride solution, followed by drying over magnesium sulfate and stripping off the solvent under reduced pressure. There was obtained 11.5 g (95%) of 5-n-propylisoxazole-3-carboxylic acid-tert-butylamide as a solid of melting point 34°-37° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[CH2:7][C:6](=O)[CH2:5][C:4]([CH3:10])([CH3:9])[NH:3]1.[CH2:12]([NH2:16])[CH2:13][CH2:14][CH3:15].[H][H]>CO.[Pt]=O>[CH3:1][C:2]1([CH3:11])[CH2:7][CH:6]([NH:16][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:5][C:4]([CH3:10])([CH3:9])[NH:3]1
Reactant: CCCCN
Reactant: [H][H]
Reactant: CC1(C)CC(=O)CC(C)(C)N1
Agent: O=[Pt]
Solvent: CO
Product: CCCCNC1CC(C)(C)NC(C)(C)C1
Yield: 95 %

Procedure:
155 g of 2,2,6,6-tetramethyl-4-piperidone and 80.0 g of butylamine were dissolved in 300 ml of methanol, and then 2.0 g of platinum oxide were added to the resulting solution, after which the solution was shaken under a pressure of 3 atmospheres of hydrogen in a medium-pressure hydrogenation apparatus at room temperature for 5 hours. At the end of this time, the platinum catalyst was filtered off, and the solvent was removed from the filtrate by distillation under reduced pressure, after which the residue was further purified by distillation under reduced pressure, to yield 201.5 g of the title compound as an oil boiling at 100° to 101° C./5 mmHg (667 Pa).
Reaction SMILES: Br[C:2]1[S:3][C:4]2[N:5]3[C:9]([C:10]([NH:14][CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:11][C:12]=2[CH:13]=1)=[N:8][CH:7]=[C:6]3[CH3:25].C(N(CC)CC)C.[CH3:33][C:34](C)([C:36]#[CH:37])C.CN(C)[CH:41]=[O:42]>[Cu]I>[OH:42][CH:41]([C:2]1[S:3][C:4]2[N:5]3[C:9]([C:10]([NH:14][CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:11][C:12]=2[CH:13]=1)=[N:8][CH:7]=[C:6]3[CH3:25])[CH2:37][CH2:36][C:34]#[CH:33]
Reactant: CN(C)C=O
Reactant: C#CC(C)(C)C
Reactant: Cc1cnc2c(NCCNC(=O)OC(C)(C)C)nc3cc(Br)sc3n12
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: C#CCCC(O)c1cc2nc(NCCNC(=O)OC(C)(C)C)c3ncc(C)n3c2s1
Temperature: 80 °C
Reaction time: 2 h
Yield: 70 %

Procedure:
A solution of N-(2-bromo-8-methyl-1-thia-4,6,8a-triaza-as-indacen-5-yl)-N-(2-tert-butoxycarbonylaminoethyl)-amine (0.030 g, 0.070 mmol) in N,N-dimethylformamide (1 mL) was added copper(I) iodide (10.5 mgs), triethylamine (0.05 mL) and 2,2-dimethyl-but-3-yne (200 μL, 3.65 mmol). Argon was bubbled in the solution, then palladium(II) triphenylphosphine (13.8 mgs) was added and the mixture was stirred at 80° C. for 2 hours. The mixture was filtered on celite and the solvent was evaporated. The residue was purified by silica gel chromatography (50% ethyl acetate in hexane) to give N-(2-(hydroxy-pentyn-5-yl)-8-methyl-1-thia-4,6,8a-triaza-as-indacen-5-yl)-N-(2-tert-butoxycarbonylaminoethyl)-amine (0.021 g, 70%). This compound was dissolved in dichloromethane (1 mL) and treated with trifluoroacetic acid (0.2 mL) for 45 minutes. The solvents were evaporated and the residue was dissolved in methanol and treated with MP-carbonate resin. This mixture was stirred at room temperature for 2 hours, then filtered. The resin was washed with methanol and the filtrate was evaporated to give Compound 393 (0.014 g, 87%). NMR (DMSO-d6, 400 MHz) δ: 7.36 (2H, s), 7.27 (1H, s), 7.25 (1H, s), 3.51 (2H, q, J=5.6 Hz), 2.87 (2H, m), 2.65 (3H, s), 1.24 (9H, s). LRMS (ESI, m/z, M+H+) 327. HRMS for C17H21N5S calcd: 327.1518, found: 327.1516.
Reaction SMILES: Cl.Cl.[N:3]1([CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH:7]=[CH:6][N:5]=[CH:4]1.[O:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[C:18](Cl)=[O:19]>>[N:3]1([CH2:8][CH2:9][CH2:10][CH2:11][NH:12][C:18]([C:14]2[O:13][CH:17]=[CH:16][CH:15]=2)=[O:19])[CH:7]=[CH:6][N:5]=[CH:4]1
Reactant: NCCCCn1ccnc1
Reactant: O=C(Cl)c1ccco1
Agent: Cl
Product: O=C(NCCCCn1ccnc1)c1ccco1

Procedure:
A portion of 1H-imidazole-1-butanamine dihydrochloride was then reacted with furoyl chloride as described in Example 1, giving the desired product, m.p. 88°-90° C.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[CH3:7][O:8][C:9]1[CH:19]=[C:18](F)[CH:17]=[CH:16][C:10]=1[C:11](OCC)=[O:12]>>[CH3:7][O:8][C:9]1[CH:19]=[C:18]([N:3]2[CH:4]=[CH:5][N:6]=[C:2]2[CH3:1])[CH:17]=[CH:16][C:10]=1[CH2:11][OH:12]
Reactant: Cc1ncc[nH]1
Reactant: CCOC(=O)c1ccc(F)cc1OC
Product: COc1cc(-n2ccnc2C)ccc1CO

Procedure:
Prepared from 2-methylimidazole and ethyl 2-methoxy-4-fluorobenzoate.
Reaction SMILES: [C:1]([CH2:3][C:4](OC)(OC)[O:5][CH3:6])#[N:2].[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O>O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO>[CH3:6][O:5][C:4](=[N:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:3][C:1]#[N:2]
Reactant: Nc1ccccc1
Reactant: COC(CC#N)(OC)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: COC(CC#N)=Nc1ccccc1
Yield: 54 %

Procedure:
In a 250-mL flask was placed 87 g (0.6 mol) of 2-cyano-1,1,1-trimethoxyethane, 46.5 g (0.5 mol) of aniline, and 1.0 g (0.005 mol) of p-toluenesulfonic acid monohydrate. The mixture was placed in a pre-heated oil bath at 120° C. and stirred rapidly. The methanol by-product of the reaction was allowed to boil off. When the internal reaction temperature reached 110° C., the reaction flask was fitted with a water aspirator vacuum take-off, and the residual methanol was removed at approximately 20 mm Hg. The crude product mixture was then distilled under high vacuum and the fraction distilling at 115°-125° C. (0.5 mm Hg) was collected to give 47.6 g (0.27 mol, 54.6% yield) of methyl-2-cyano-N-phenylacetimidate as a light yellow liquid, which was characterized by NMR and mass spectral data. HPLC analysis showed this material to be 96% pure. Elemental analysis: Calculated: C, 68.95; H, 5.79; N, 16.08. Found: C, 66.80, H, 5.72, N, 15.36.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]2[N:8]=[C:9]([NH:11][CH:12]([CH3:14])[CH3:13])[S:10][C:4]=2[CH:3]=1.[C:15]1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:44]([O-:47])([O-])=[O:45].[K+].[K+]>CO.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:12]([NH:11][C:9]1[S:10][C:4]2[CH:3]=[C:2]([C:44]([O:47][CH3:15])=[O:45])[N:7]=[CH:6][C:5]=2[N:8]=1)([CH3:14])[CH3:13]
Reactant: CC(C)Nc1nc2cnc(Cl)cc2s1
Reactant: O=C([O-])[O-]
Reactant: c1ccc(P(CCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CO
Solvent: CN(C)C=O
Product: COC(=O)c1cc2sc(NC(C)C)nc2cn1
Temperature: 25 °C
Yield: 301.2 %

Procedure:
A solution of 6-chloro-N-isopropylthiazolo[4,5-c]pyridin-2-amine (0.24 g, 1.05 mmol, 1.0 eq.), Pd(OAc)2 (0.0313 g, 0.139 mmol, 0.1 eq.), 1,3-bis(diphenylphosphino)propane (0.0443 g, 0.107 mmol, 0.1 eq.) and K2CO3 (0.2214 g, 1.60 mmol, 1.5 eq.) in MeOH (2.6 mL) and DMF (1.3 mL) was stirred under an atmosphere of CO inside a bomb (40 psi) at 91° C. overnight. After cooling to room temperature, the reaction mixture was filtered through Celite and rinsed with MeOH. The filtrate was concentrated in vacuo, diluted with EtOAc and water. The layers were separated, and the organic layer was washed with brine and 10% aqueous LiCl, dried over Na2SO4, filtered and concentrated in vacuo. The residue was triturated with CH2Cl2:MeOH (10:0.3) to give methyl 2-(isopropylamino)thiazolo[4,5-c]pyridine-6-carboxylate as a white solid (0.081 g, 31% yield).
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10](=[O:19])[N:11]([CH3:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:5][CH:4]=1.O[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1>>[N:23]1[CH:24]=[CH:25][CH:26]=[C:21]([O:1][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([O:9][C:10](=[O:19])[N:11]([CH3:18])[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:7][CH:8]=2)[CH:22]=1
Reactant: Oc1cccnc1
Reactant: CN(C(=O)Oc1ccc(CO)cc1)c1ccccc1
Product: CN(C(=O)Oc1ccc(COc2cccnc2)cc1)c1ccccc1
Yield: 43 %

Procedure:
The title compound was prepared in 43% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 3-hydroxypyridine. 1H NMR (400 MHz; CDCl3): δ 3.44 (br s, 3H), 5.12 (s, 2H), 7.17 (br s, 2H), 7.27–7.46 (m, 9H), 8.29 (br s, 1H), 8.49 (br s, 1H); HPLC-MS: m/z=335.0 (M+1); Rt=2.74 min.
Reaction SMILES: [S:1](=[O:5])(=[O:4])([OH:3])[O-:2].[C:6]1([C:12]2[CH:17]=[C:16](C3C=CC=CC=3)C=C(C3C=CC=CC=3)[O+]=2)[CH:11]=C[CH:9]=[CH:8][CH:7]=1.C(O)C.[CH2:33]([C:43]1[CH:49]=[CH:48][C:46]([NH2:47])=[CH:45][CH:44]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42].NC1C=CC=CC=1>C(#N)C>[S:1](=[O:3])(=[O:2])([OH:5])[O-:4].[CH2:33]([C:43]1[CH:44]=[CH:45][C:46]([N+:47]2[C:17]([CH3:16])=[CH:12][C:6]([CH3:11])=[CH:7][C:8]=2[CH3:9])=[CH:48][CH:49]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]
Reactant: CCCCCCCCCCc1ccc(N)cc1
Reactant: c1ccc(-c2cc(-c3ccccc3)[o+]c(-c3ccccc3)c2)cc1
Agent: O=S(=O)([O-])O
Solvent: Nc1ccccc1
Solvent: CC#N
Solvent: CCO
Product: CCCCCCCCCCc1ccc(-[n+]2c(C)cc(C)cc2C)cc1

Procedure:
In a 500-ml round-bottom flask is placed 2.03 g (0.005 mole) of 2,4,6-triphenylpyrylium bisulfate. To this is added 150 ml of ethanol followed by 2.34 g (0.01 mole) of p-decylaniline. This mixture is refluxed for about 8 hours and allowed to cool. A quantity of the starting aniline precipitates and is removed by filtration. The ethanol is then removed to give a yellow waxy material which is washed with ether to give a white powder. This material is then dissolved in acetonitrile to cause the remaining aniline to precipitate. The acetonitrile is removed to give the desired product which is then rinsed with ether to remove any residual acetonitrile. The yield is 1.77 g (0.0028 mole) of 2,4,6-triphenylpyridinium bisulfate as confirmed by nuclear magnetic resonance (1H) and elemental analysis.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[N:8]([CH3:22])[C:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C:10]=3[C:5]2=[CH:4][CH:3]=1.[CH2:23]([N:31]1[CH2:36][CH2:35][NH:34][C:33](=[O:37])[CH2:32]1)[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH3:22][N:8]1[C:6]2=[N:7][C:2]([N:34]3[CH2:35][CH2:36][N:31]([CH2:23][CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:32][C:33]3=[O:37])=[CH:3][CH:4]=[C:5]2[C:10]2[CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14][C:9]1=2
Reactant: Cn1c2c(c3ccc(Br)nc31)CN(C(=O)OC(C)(C)C)CC2
Reactant: O=C1CN(CCc2ccccc2)CCN1
Product: Cn1c2c(c3ccc(N4CCN(CCc5ccccc5)CC4=O)nc31)CN(C(=O)OC(C)(C)C)CC2
Yield: 67.5 %

Procedure:
tert-Butyl 2-bromo-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (86 mg, 0.23 mmol) and 4-phenethylpiperazin-2-one (56 mg, 0.27 mmol) were reacted according to Example 2 (step e) to provide the title compound (76 mg, 67%) as a yellow powder: ESI MS m/z 490 [M+H]+.
Reaction SMILES: C(O)C.Br[C:5]1[CH:6]=[CH:7][C:8]2[N:14]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[O:22][CH3:23])[CH2:13][CH2:12][C:11]([C:24]([O:26][CH3:27])=[O:25])=[CH:10][C:9]=2[CH:28]=1.B([O-])([O-])O[C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH3:40])=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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.O>[CH2:38]([O:37][C:34]1[CH:35]=[CH:36][C:31]([C:5]2[CH:6]=[CH:7][C:8]3[N:14]([CH2:15][C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[O:22][CH3:23])[CH2:13][CH2:12][C:11]([C:24]([O:26][CH3:27])=[O:25])=[CH:10][C:9]=3[CH:28]=2)=[CH:32][CH:33]=1)[CH2:39][CH3:40]
Reactant: CCCOc1ccc(OB([O-])[O-])cc1
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(Cc2ccccc2OC)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: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: CCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3Cc2ccccc2OC)cc1
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 81.9 %

Procedure:
In toluene (25 ml), ethanol (2.5 ml) and water (2.5 ml) were suspended methyl 7-bromo-1-(2-methoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylate (712 mg), 4-propoxyphenyl borate (416 mg) and potassium carbonate (636 mg), and the suspension was stirred under argon atmosphere for 30 minutes. Then, to the suspension was added tetrakistriphenylphosphinepalladium (143 mg) and the mixture was heated under argon atmosphere at 100° C. for 5 hours. After allowing to cool, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified with silica gel column chromatography (hexane:ethyl acetate=3:1) to give methyl 7-(4-propoxyphenyl)-1-(2-methoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylate (663 mg) as yellow oil.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][N:14]([CH2:41][CH2:42][NH:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[CH2:15][CH2:16][CH2:17][C@H:18]([N:26]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:19]([O:21]C(C)(C)C)=[O:20])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(OCC)C>C(OCC)(=O)C>[CH2:47]([O:46][C:44]([NH:43][CH2:42][CH2:41][N:14]([CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])[CH2:15][CH2:16][CH2:17][C@H:18]([N:26]([C:27]([O:29][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:28])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:19]([OH:21])=[O:20])=[O:45])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1
Reactant: CC(C)(C)OC(=O)[C@H](CCCN(CCNC(=O)OCc1ccccc1)CCNC(=O)OCc1ccccc1)N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)[C@@H](CCCN(CCNC(=O)OCc1ccccc1)CCNC(=O)OCc1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 77.7 %

Procedure:
To a solution of tert-butyl (2S)-5-[bis(2-{[(benzyloxy)carbonyl]amino}ethyl)amino]-2-{bis[(tert-butoxy)carbonyl]amino}pentanoate XXXI (3.00 g, 4.04 mmol) in ethyl acetate (20 mL) was added HCl (3.5 M solution in EtOAc, 20 mL). The reaction mixture was stirred for 30 min at r.t. before adding ethyl ether (about 50 mL). The precipitate was filtered and washed with ether to give (2S)-5-[bis(2-{[(benzyloxy)carbonyl]amino}ethyl)amino]-2-{bis[(tert-butoxy)carbonyl]amino}pentanoic acid as a white crystalline solid (1.82 g, 3.14 mmol, 78% yield).
Reaction SMILES: [C:1]([SiH2:5][O:6][C:7]([CH3:17])([CH3:16])[C:8]1[O:9][CH:10]=[C:11]([OH:15])[C:12](=[O:14])[CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[Br:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]Br>CN(C=O)C>[Br:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][O:15][C:11]1[C:12](=[O:14])[CH:13]=[C:8]([C:7]([CH3:17])([CH3:16])[O:6][SiH2:5][C:1]([CH3:4])([CH3:2])[CH3:3])[O:9][CH:10]=1
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1cc(=O)c(O)co1
Reactant: BrCCCCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)[SiH2]OC(C)(C)c1cc(=O)c(OCCCCCBr)co1
Temperature: 50 °C
Reaction time: 0.08 h
Yield: 53 %

Procedure:
2-(tert-Butyl-dimethyl-silanyloxymethyl)-5-hydroxy-4H-pyran-4-one 6 (1.50 g, 5.85 mmol) was charged in a 100 mL round-bottomed flask equipped with a magnetic stirrer and under inert atmosphere. Anhydrous DMF (25 mL) and Cs2CO3 (2.10 g, 6.44 mmol) were successively added. After 5 min, 1,5-dibromopentane (2.39 mL, 17.55 mmol) was added via syringe at room temperature. The reaction mixture Novas heated at 50° C. for 3 h. After cooling and filtration DMF was removed in vacuo. The crude oil was purified by chromatography on silica using as eluent EtOAc:cyclohexane=20:80 then 30:70. After evaporation, 5-5-bromo-pentyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-4H-pyran-4-one 7 was obtained (1.25 g, 53% yield) as a white solid.
Reaction SMILES: [Br:1][C:2]1[C:7]2=[N:8][S:9][N:10]=[C:6]2[C:5]([CH2:11]Br)=[CH:4][CH:3]=1.C(=O)([O-])[O-:14].[K+].[K+]>O>[Br:1][C:2]1[C:7]2[C:6](=[N:10][S:9][N:8]=2)[C:5]([CH2:11][OH:14])=[CH:4][CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: BrCc1ccc(Br)c2nsnc12
Agent: [K+]
Solvent: O
Product: OCc1ccc(Br)c2nsnc12
Temperature: 110 °C
Reaction time: 16 h
Yield: 87.5 %

Procedure:
A mixture of 4-bromo-7-bromomethyl-benzo[1,2,5]thiadiazole (29.05 g) (Example II), potassium carbonate (65.2 g) and water (400 ml) was stirred at 110° C. for 16 hours. The reaction mixture was cooled to ambient temperature and quenched by addition of aqueous hydrochloric acid (2M) (400 ml). Ethyl acetate (600 ml) was added to the mixture. The phases were separated and the organic layer was washed successively with aqueous hydrochloric acid (2M) (400 ml), water (250 ml) and brine (250 ml), dried over sodium sulfate and concentrated to give (7-bromo-benzo[1,2,5]thiadiazol-4-yl)-methanol (20.22 g) as a orange solid. 1H-NMR (400 MHz, CDCl3): 7.87 (d, 1H), 7.57 (d, 1H), 5.14 (s, 2H) ppm.