Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]3[CH:17]=[CH:16][C:15]4[C:7]3=[C:8]([CH:12]=[CH:13][CH:14]=4)[C:9](=O)[NH:10][C:4]=2[CH:3]=1.COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:29]2)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]3[CH:17]=[CH:16][C:15]4[C:7]3=[C:8]([CH:12]=[CH:13][CH:14]=4)[C:9](=[S:29])[NH:10][C:4]=2[CH:3]=1
Reactant: O=C1Nc2cc(Br)ccc2-n2ccc3cccc1c32
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: S=C1Nc2cc(Br)ccc2-n2ccc3cccc1c32
Reaction time: 8 h
Yield: 71.5 %

Procedure:
A mixture of 9-bromobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6(7H)-one (12.8 g), 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (8.3 g), and toluene (500 ml) was refluxed for 2 hrs. The reaction mixture was allowed to stand overnight at room temperature. The precipitate was collected, washed with hexane, and dried overnight under vacuum at 40° C. to provide 9.6 g, (71.5%) of product. Recrystallization from chloroform gave the analytical sample, mp 214°-215° C.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([NH:31][C@@H:32]2[C@@H:37]3[CH2:38][C@@H:34]([CH:35]=[CH:36]3)[C@@H:33]2[C:39]([NH2:41])=[O:40])=[C:11]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21](CN4CCOCC4)=[CH:20][CH:19]=3)[NH:15][C:12]2=[N:13][CH:14]=1.NC1C(N)=C(N[C@H]2[C@H]3C[C@H](C=C3)[C@H]2C(N)=O)C(Cl)=CN=1.[CH3:62][N:63]1[CH2:68][CH2:67][N:66](C2C=CC(C=O)=CC=2)[CH2:65][CH2:64]1>>[Cl:8][C:9]1[C:10]([NH:31][C@H:32]2[C@H:37]3[CH2:38][C@H:34]([CH:35]=[CH:36]3)[C@H:33]2[C:39]([NH2:41])=[O:40])=[C:11]2[N:17]=[C:16]([C:18]3[CH:19]=[CH:20][C:21]([N:66]4[CH2:67][CH2:68][N:63]([CH3:62])[CH2:64][CH2:65]4)=[CH:22][CH:23]=3)[NH:15][C:12]2=[N:13][CH:14]=1
Reactant: NC(=O)[C@@H]1[C@H](Nc2c(Cl)cnc3[nH]c(-c4ccc(CN5CCOCC5)cc4)nc23)[C@H]2C=C[C@@H]1C2
Reactant: CN1CCN(c2ccc(C=O)cc2)CC1
Agent: NC(=O)[C@H]1[C@@H](Nc2c(Cl)cnc(N)c2N)[C@@H]2C=C[C@H]1C2
Solvent: O=C(O)C(F)(F)F
Product: CN1CCN(c2ccc(-c3nc4c(N[C@@H]5[C@H](C(N)=O)[C@H]6C=C[C@@H]5C6)c(Cl)cnc4[nH]3)cc2)CC1
Yield: 66 %

Procedure:
In the same fashion as for Compound III, (1R,2R,3S,4S)-3-(2,3-Diamino-5-chloro-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide and 4-(4-Methyl-piperazin-1-yl)-benzaldehyde were reacted to produce the title compound (66%). 1H NMR (d-chloroform): 15.63 (br s, 1H) 8.36 (d, J=9 Hz, 1H), 8.02 (d, J=9 Hz, 2H), 7.78 (s, 1H), 7.03 (d, J=9 Hz, 2H), 6.48 (m, 1H), 6.42 (m, 1H), 5.95 (s, 1H), 5.59 (s, 1H), 5.54 (t, J=8 Hz, 1H), 3.38-3.92 (m, 8H), 3.17 (s, 1H), 3.04 (m, 1H), 3.02 (s, 1H), 2.91 (s, 3H), 2.68 (d, J=9 Hz, 1H), 2.32 (d, J=9 Hz, 1H), 1.67 (d, J=9 Hz, 1H). MS: 478.15 (M+H). HPLC retention time: 1.79 minutes (G Method).
Reaction SMILES: [C:1]([CH:6]1[C:11](=[O:12])[CH2:10][CH:9]([CH2:13][CH2:14][S:15][CH3:16])[CH2:8][C:7]1=[O:17])(=O)[CH2:2][CH2:3][CH3:4].[CH2:18]([O:21][NH2:22])[CH:19]=[CH2:20]>C(O)C>[CH2:18]([O:21][NH:22][C:1](=[C:6]1[C:11](=[O:12])[CH2:10][CH:9]([CH2:13][CH2:14][S:15][CH3:16])[CH2:8][C:7]1=[O:17])[CH2:2][CH2:3][CH3:4])[CH:19]=[CH2:20]
Reactant: CCCC(=O)C1C(=O)CC(CCSC)CC1=O
Reactant: C=CCON
Solvent: CCO
Product: C=CCONC(CCC)=C1C(=O)CC(CCSC)CC1=O
Yield: 95 %

Procedure:
2.6 g of 2- butyryl-5-(2-methylthioethyl)-cyclohexane-1,3-dione was allowed to react with 0.8 g of allyloxyamine at room temperature for 10 hours in 20 ml of ethanol. After completion of the reaction, the resulting reaction solution was treated as in Example 1 to obtain 3 g of the desired compound as colorless oily material. nD27 1.5402
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[N:8]([C:9]([C:11]2[N:12]=[C:13]([CH3:23])[S:14][C:15]=2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)=[O:10])[CH2:7][C@H:6]2[C@@H:4]1[CH2:5]2.[N:24]1[CH:25]=[C:26]([C:33](O)=[O:34])[N:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=12>>[Cl:22][C:18]1[CH:17]=[C:16]([C:15]2[S:14][C:13]([CH3:23])=[N:12][C:11]=2[C:9]([N:8]2[CH2:7][C@H:6]3[C@H:4]([CH2:5]3)[C@H:3]2[CH2:2][NH:1][C:33]([C:26]2[N:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]3=[N:24][CH:25]=2)=[O:34])=[O:10])[CH:21]=[CH:20][CH:19]=1
Reactant: O=C(O)c1cnc2ccccn12
Reactant: Cc1nc(C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CN)c(-c2cccc(Cl)c2)s1
Product: Cc1nc(C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CNC(=O)c2cnc3ccccn23)c(-c2cccc(Cl)c2)s1

Procedure:
prepared by reaction of ((1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-[5-(3-chloro-phenyl)-2-methyl-thiazol-4-yl]-methanone with Imidazo[1,2-a]pyridine-3-carboxylic acid. LC-MS (basic): tR=0.83 min; [M+H]+=492.2.
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]2[C@:20]([CH3:24])([C@@H:21]([CH3:23])[CH:22]=1)[C@@H:19]1[C@H:10]([C@H:11]3[C@@:15]([CH2:17][CH2:18]1)([CH3:16])[C:14](=[O:25])[CH2:13][CH2:12]3)[CH2:9][CH2:8]2)(=O)C.[Br:26]N1C(C)(C)C(=O)N(Br)C1=O>O1CCOCC1.O>[Br:26][C@@H:22]1[C@H:21]([CH3:23])[C@@:20]2([CH3:24])[C:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C:14]2=[O:25])=[CH:6][C:5]1=[O:4]
Reactant: CC(=O)OC1=C[C@H](C)[C@@]2(C)C(=C1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Solvent: O
Solvent: C1COCCO1
Product: C[C@H]1[C@@H](Br)C(=O)C=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21C
Temperature: 25 °C
Reaction time: 1 h
Yield: 193.6 %

Procedure:
Under ice cooling, a suspension of 5.18 g of 3-acetoxy-1α-methylandrosta-2,4-dien-17-one in 50 ml of dioxane and 100 ml of water is combined in portions with 2.2 g of 1,3-dibromo-5,5-dimethylhydantoin and stirred for one hour at room temperature. Subsequently, the mixture is precipitated into 1 liter of water saturated with sodium chloride, 2.7 g of sodium sulfite is added, and the mixture is stirred for 60 minutes. The precipitated residue is filtered off, washed free of chloride with water, and dried, thus obtaining 5.65 g of a mixture of 2β-bromo-1α-methyl-4-androstene-3,17-dione and 2β-bromo-1α-methyl-4-androstene-3,17-dione.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([S:16][CH3:17])[N:12]([CH3:18])[C:11]2=[O:19])=[CH2:5])C.O.C1C(=O)N([Br:28])C(=O)C1>C1COCC1>[Br:28][CH2:3][C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([S:16][CH3:17])[N:12]([CH3:18])[C:11]2=[O:19])=[O:5]
Reactant: O=C1CCC(=O)N1Br
Reactant: C=C(OCC)c1cccc2c(=O)n(C)c(SC)nc12
Solvent: C1CCOC1
Solvent: O
Product: CSc1nc2c(C(=O)CBr)cccc2c(=O)n1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Et3N (0.094 mL, 0.674 mmol) and TBSOTf (0.131 mL, 0.570 mmol) were sequentially added to a yellow solution of 8-acetyl-3-methyl-2-(methylthio)quinazolin-4(3H)-one (128.7 mg, 0.518 mmol) in DCM (2.7 mL) at 0° C., and the resulting light-yellow solution was stirred at 0° C. for 30 min. The mixture was partitioned between DCM (50 mL) and saturated aq. NaHCO3 (20 mL). The organic layer was separated, and the aq. layer was extracted with DCM (30 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to provide crude 8-(1-((tert-butyldimethylsilyl)oxy)vinyl)-3-methyl-2-(methylthio)quinazolin-4(3H)-one as a peach-colored solid. This material was combined with 8-(1-ethoxyvinyl)-3-methyl-2-(methylthio)quinazolin-4(3H)-one (35.5 mg, 0.128 mmol), and the resulting mixture was taken up in THF (2.70 mL). Water (0.149 mL, 8.29 mmol) and NBS (115 mg, 0.648 mmol) were sequentially added at 25° C., and the resulting solution was stirred at 25° C. for 30 min. The mixture was partitioned between Et2O (50 mL) and water (30 mL). The organic layer was separated, sequentially washed with saturated aq. NaHCO3 (20 mL), water (20 mL), and brine (20 mL), then dried over Na2SO4, filtered, and concentrated in vacuo to provide crude 8-(2-bromoacetyl)-3-methyl-2-(methylthio)quinazolin-4(3H)-one as an off-white solid. NH4OAc (200 mg, 2.59 mmol) and piperidine-2,4-dione (88 mg, 0.777 mmol) were added to this solid, and the resulting mixture was taken up in EtOH (2.70 mL) and heated under argon in a sealed flask at 40° C. for 16 h. The reaction suspension was vacuum filtered, and the collected solid was washed with MeOH (20 mL) and dried in vacuo. The residue was triturated with DMSO (2.0 mL), and the resulting suspension was vacuum filtered. The collected solid was sequentially washed with MeOH (5 mL) and DCM (5 mL) and dried in vacuo to provide 3-methyl-2-(methylthio)-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinazolin-4(3H)-one (57.1 mg, 0.168 mmol, 26% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.67 (1H, br. s.), 8.05 (1H, dd, J=7.6, 1.2 Hz), 7.95 (1H, dd, J=7.8, 1.0 Hz), 7.44 (1H, t, J=7.8 Hz), 7.03 (1H, d, J=2.3 Hz), 6.96 (1H, br. s.), 3.56 (3H, s), 3.41 (2H, td, J=6.8, 2.2 Hz), 2.85 (2H, t, J=6.9 Hz), 2.74 (3H, s). m/z (ESI, +ve) 341.1 (M+H)+.
Reaction SMILES: N1(C2C=CC([C:13]3[CH:14]=[CH:15][C:16]4[O:22][CH2:21][CH2:20][C:19]([C:23](O)=[O:24])=[CH:18][C:17]=4[CH:26]=3)=CC=2)CCCCC1.C[N:28](CC1C=CC(N)=CC=1)C1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[O:22]1[C:16]2[CH:15]=[CH:14][CH:13]=[CH:26][C:17]=2[CH:18]=[C:19]([C:23]([NH2:28])=[O:24])[CH2:20][CH2:21]1
Reactant: O=C(O)C1=Cc2cc(-c3ccc(N4CCCCC4)cc3)ccc2OCC1
Reactant: CN(Cc1ccc(N)cc1)C1CCOCC1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: NC(=O)C1=Cc2ccccc2OCC1
Temperature: 25 °C
Yield: 221.6 %

Procedure:
To a solution of 7-(4-piperidinophenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.15g), 4-(N-methyl-N-(tetrahydropyran-4-yl)aminomethyl)aniline (0.1g) and 1hydroxy-benzotriazole (0.07g) in dimethylformamide (10ml) was added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.13g) under ice-cooling. Under nitrogen atmosphere, the mixture was warmed to room temperature. To the mixture were added 4-dimethylaminopyridine (catalytic amount) and triethylamine (0.18ml), and the mixture was stirred over night. The solvent was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated to give crude crystals, which were recrystallized from ethyl acetate-hexane to give 7-(4-piperidinophenyl)-N-(4-((N-methyl-N-tetrahydro-pyran-4-yl)amino)-methyl)-phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 151) (0.18g) as colorless crystals.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH2:6][CH3:7])=[O:3].[O:8]([C:18]1[CH:29]=[CH:28][C:21]2[C:22]([CH3:27])=[CH:23][C:24](=[O:26])[O:25][C:20]=2[CH:19]=1)[C@@H:9]1[S:17][CH2:16][C@@H:14]([OH:15])[C@H:12]([OH:13])[C@H:10]1[OH:11]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH2:5]([O:4][C:2]([O:11][C@@H:10]1[C@@H:12]([O:13][C:2]([O:4][CH2:5][CH2:6][CH3:7])=[O:3])[C@H:14]([O:15][C:2]([O:4][CH2:5][CH2:6][CH3:7])=[O:3])[CH2:16][S:17][C@H:9]1[O:8][C:18]1[CH:29]=[CH:28][C:21]2[C:22]([CH3:27])=[CH:23][C:24](=[O:26])[O:25][C:20]=2[CH:19]=1)=[O:3])[CH2:6][CH3:7]
Reactant: Cc1cc(=O)oc2cc(O[C@@H]3SC[C@@H](O)[C@H](O)[C@H]3O)ccc12
Reactant: CCCOC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CCCOC(=O)O[C@@H]1[C@@H](OC(=O)OCCC)[C@H](OC(=O)OCCC)CS[C@H]1Oc1ccc2c(C)cc(=O)oc2c1
Reaction time: 1 h

Procedure:
A solution of 100 mg (0.8.10−3 mol) of 4-dimethylaminopyridine in 12 ml of pyridine is prepared and 2.1 ml (18.7.10−3 mol) of propyl chloroformate are added at 0° C., followed by 1 g (3.1.10−3 mol) of 4-methyl-2-oxo-2H-1-benzopyran-7-yl 5-thio-β-D-xylopyranoside. The reaction mixture is stirred for 1 hour, a further 1 ml (8.9.10−3 mol) of propyl chloroformate is then added and stirring is continued for 1 hour. The mixture is then hydrolyzed in ice water and extracted with ethyl acetate. The organic phase is washed with dilute hydrochloric acid solution and then with water, dried and finally concentrated under reduced pressure. The residue is purified by chromatography on silica gel using a toluene/ethyl acetate mixture (4/1; v/v) as the eluent. The pure product fraction is crystallized from an ethyl acetate/ diethyl ether mixture to give 1.13 g of the expected product in the form of a fine and light white solid (yield=63%).
Reaction SMILES: [NH2:1][C@H:2]([CH3:14])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][CH3:13])[CH:5]=1.C[Si](C)(C)NC(=O)C.[C:23]1([O:33][CH2:34][CH:35]2[O:37][CH2:36]2)[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1.Cl.[OH-].[Na+]>CS(C)=O>[CH3:13][O:12][C:6]1[CH:5]=[C:4]([CH2:3][CH:2]([NH:1][CH2:36][CH:35]([OH:37])[CH2:34][O:33][C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[CH:25][CH:24]=2)[CH3:14])[CH:9]=[CH:8][C:7]=1[O:10][CH3:11]
Reactant: COc1ccc(C[C@@H](C)N)cc1OC
Reactant: c1ccc2c(OCC3CO3)cccc2c1
Agent: CC(=O)N[Si](C)(C)C
Agent: Cl
Agent: [Na+]
Solvent: CS(C)=O
Product: COc1ccc(CC(C)NCC(O)COc2cccc3ccccc23)cc1OC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 4.20 g of (R)-2-Amino-1-(3,4-dimethoxyphenyl)propane and 3.11 g of N-(trimethylsilyl)acetamide in 20 ml of dimethylsulfoxide is stirred at room temperature for 1 hour. A solution of 4.05 g of (1-naphthyl)glycidyl ether in 3 ml of dimethylsulfoxide is added to the above mixture and the resulting mixture is heated at 65° C. to 70° C. for 20 hours, cooled, poured into a mixture of ice and concentrated hydrochloric acid, stirred, basified with 10N sodium hydroxide and extracted with ethyl acetate. The ethyl acetate extract is washed with brine, dried, filtered and evaporated to yield 1-[(3,4-dimethoxyphenyl)-2-propyl]amino-3-(1- naphthyloxy)propan-2-ol.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[S:12]([NH:15][CH3:16])(=[O:14])=[O:13].[F:17][C:18]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[CH:20][C:19]=1[C:33]1[CH:34]=[N:35][C:36]([NH2:39])=[N:37][CH:38]=1>>[NH2:39][C:36]1[N:37]=[CH:38][C:33]([C:19]2[CH:20]=[CH:21][C:22]([C:2]3[C:3]([S:12]([NH:15][CH3:16])(=[O:14])=[O:13])=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:7]=3)=[CH:23][C:18]=2[F:17])=[CH:34][N:35]=1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)nc3)c(F)c2)OC1(C)C
Reactant: CNS(=O)(=O)c1cc(C(F)(F)F)ccc1Br
Product: CNS(=O)(=O)c1cc(C(F)(F)F)ccc1-c1ccc(-c2cnc(N)nc2)c(F)c1

Procedure:
The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-methyl-5-(trifluoromethyl)benzenesulfonamide and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C18H14F4N4O2S, 426.08; m/z found, 427.0 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.57-8.52 (d, J=1.4, 2H), 8.33-8.27 (m, 1H), 8.02-7.94 (m, 1H), 7.66-7.60 (d, J=7.9, 1H), 7.60-7.52 (m, 1H), 7.38-7.31 (m, 2H), 2.46 (s, 3H).
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:20])[NH:6][C:7](=[O:19])[NH:8][C:9]=1[S:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=1)([CH3:3])[CH3:2].C1(C)C=CC(S(O[CH2:31][CH:32]2[CH2:35][CH2:34][CH2:33]2)(=O)=O)=CC=1>>[CH:32]1([CH2:31][N:8]2[C:9]([S:10][C:11]3[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:20])[NH:6][C:7]2=[O:19])[CH2:35][CH2:34][CH2:33]1
Reactant: Cc1cc(C)cc(Sc2[nH]c(=O)[nH]c(=O)c2C(C)C)c1
Reactant: Cc1ccc(S(=O)(=O)OCC2CCC2)cc1
Product: Cc1cc(C)cc(Sc2c(C(C)C)c(=O)[nH]c(=O)n2CC2CCC2)c1
Yield: 41 %

Procedure:
5-Isopropyl-6-(3,5-dimethylphenyl)thio-2,4-pyrimidinedione and (cyclobutyl)methyl para-toluenesulfonate were reacted by the same way with the example 1 to obtain the titled compound (147 mg, yield: 41.0%).
Reaction SMILES: C(OC(OC(OCC)=O)=O)C.C(OC([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:26]([F:29])([F:28])[F:27])[CH:24]=2)[C:19]([NH2:30])=[N:18]1)=O)C>C(O)C>[NH2:30][C:19]1[C:20]2[C:25](=[CH:24][C:23]([C:26]([F:28])([F:27])[F:29])=[CH:22][CH:21]=2)[NH:17][N:18]=1
Reactant: CCOC(=O)n1nc(N)c2ccc(C(F)(F)F)cc21
Agent: CCOC(=O)OC(=O)OCC
Solvent: CCO
Product: Nc1n[nH]c2cc(C(F)(F)F)ccc12

Procedure:
Analogously to Example 22, 0.04 mol of 3-amino-6-trifluoromethylindazole and 50 ml of pyrocarbonic acid diethyl ester in 25 ml of ethanol give 3-amino-6-trifluoromethylindazole-1-carboxylic acid ethyl ester (melting point: 168°-169° C; 64% of theory) in 2 hours at 80° C.
Reaction SMILES: C[CH:2]([CH3:38])[C@@H:3]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=4)=[O:25])=[CH:19][CH:18]=3)[CH:14]=2)[C:9]1=[O:37])C(OC)=O.BrC1C=C2C(=CC=1)C(=O)N(CCC[C:53]([O:55][CH3:56])=[O:54])C2.CC1(C)C(C)(C)OB(C2C=CC(NC(NC3C=CC=C(C(F)(F)F)C=3)=O)=CC=2)O1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[O:37]=[C:9]1[C:10]2[C:15](=[CH:14][C:13]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:34])([F:36])[F:35])[CH:28]=4)=[O:25])=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[CH2:16][N:8]1[CH2:3][CH2:2][CH2:38][C:53]([O:55][CH3:56])=[O:54]
Reactant: COC(=O)CCCN1Cc2cc(Br)ccc2C1=O
Reactant: COC(=O)[C@@H](C(C)C)N1Cc2cc(-c3ccc(NC(=O)Nc4cccc(C(F)(F)F)c4)cc3)ccc2C1=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC1(C)OB(c2ccc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2)OC1(C)C
Solvent: ClCCl
Product: COC(=O)CCCN1Cc2cc(-c3ccc(NC(=O)Nc4cccc(C(F)(F)F)c4)cc3)ccc2C1=O

Procedure:
The compound of example 375 was prepared analogous to compound of example 360 by reaction of the compound of example 374, compound of example 357 and Pd(dppf)Cl2: CH2Cl2.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].Br[CH:21]1[CH2:25][CH2:24][N:23]([CH3:26])[C:22]1=[O:27].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:26][N:23]1[CH2:24][CH2:25][C@H:21]([O:1][C:2]2[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])[C:22]1=[O:27]
Reactant: COC(=O)c1cc(O)cc(OCc2ccccc2)c1
Reactant: CN1CCC(Br)C1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc(OCc2ccccc2)cc(O[C@H]2CCN(C)C2=O)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Methyl 3-hydroxy-5-phenylmethoxy-benzoate (CAS no. 54915-31-0) (10.3 g, 40 mmol) and 3-bromo-1-methyl-pyrrolidin-2-one (Intermediate 4) (8.54 g, 48 mmol) were dissolved in DMF, treated with potassium carbonate (12.1 g, 88 mmol) and stirred at room temperature for 16 hours and then at 50° C. for 3 hours. The DMF was evaporated under reduced pressure and the residue partitioned between ethyl acetate (100 mL) and water (30 mL). The organic layer was separated, washed with brine (30 mL), dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with 0-100% ethyl acetate in hexane to give the racemic product (8.7 g). The desired product was separated from its enantiomer by chiral HPLC using Merck 50 mm 20 μm Chiralpak AS—No ASV00SC JG001 and ASV000SC BD004 columns in series, eluting with 30% ethylacetate in isohexane at a flow rate of 60 mL/min, using 9 separate injections of 70 mL of a 14 mg/ml solution of the racemate in ethanol (32 mL) and isohexane (38 mL) to afford the product (3.6 g, 41%) which eluted before its enantiomer. 1H NMR δ (300 MHz, CDCl3) 2.06-2.20 (m, 1H), 2.51-2.63 (m, 1H), 2.94 (s, 3H), 3.31-3.54 (m, 2H), 3.89 (s, 3H), 4.87 (t, 1H), 5.08 (s, 2H), 6.90 (t, 1H), 7.27-7.46 (m, 7H).
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:13]1([C:19]2[C:20]3[CH:21]=[CH:22][C:23]([C:43]([OH:45])=O)=[CH:24][C:25]=3[N:26]3[CH2:32][C:31]([C:33]([O:35][CH3:36])=[O:34])=[CH:30][C:29]4[CH:37]=[C:38]([O:41][CH3:42])[CH:39]=[CH:40][C:28]=4[C:27]=23)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[S:46]([NH2:50])([NH2:49])(=[O:48])=[O:47].C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O.C(Cl)Cl>[NH2:49][S:46]([NH:50][C:43]([C:23]1[CH:22]=[CH:21][C:20]2[C:19]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]3)=[C:27]3[C:28]4[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][C:29]=4[CH:30]=[C:31]([C:33]([O:35][CH3:36])=[O:34])[CH2:32][N:26]3[C:25]=2[CH:24]=1)=[O:45])(=[O:48])=[O:47]
Reactant: COC(=O)C1=Cc2cc(OC)ccc2-c2c(C3CCCCC3)c3ccc(C(=O)O)cc3n2C1
Reactant: NS(N)(=O)=O
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: C1CCOC1
Product: COC(=O)C1=Cc2cc(OC)ccc2-c2c(C3CCCCC3)c3ccc(C(=O)NS(N)(=O)=O)cc3n2C1
Temperature: 60 °C
Reaction time: 0.17 h
Yield: 91.4 %

Procedure:
1,1′-Carbonyldiimidazole (1.23 g, 7.60 mmol) was added to a slurry of 13-cyclohexyl-3-methoxy-6-(methoxycarbonyl)-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (2.6 g, 5.8 mmol) in THF (11 mL). The reaction mixture was heated at 60° C. for 1.5 h, cooled to rt, treated with sulfamide (1.12 g, 11.7 mmol), stirred 10 min and then treated with the dropwise addition of a solution of DBU (1.8 mL, 11.7 mmol) in THF (3 mL). The reaction mixture was stirred at rt for 3 h, diluted with EtOAc (80 mL) and CH2Cl2 (100 mL) and concentrated to dryness. The residue was diluted with CH2Cl2 (100 mL) and washed with 1N HCl (aq.) (2×100 mL). The combined aqueous layers were extracted with CH2Cl2 (100 mL) and the combined organic layers were washed with ½ saturated brine (˜50 mL), dried (MgSO4), filtered and concentrated. The residue was stirred with Et2O (˜75 mL) for lh and the solids were collected by filtration, rinsed with Et2O and dried to yield methyl 10-((aminosulfonyl)carbamoyl)-13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylate (2.8 g, 5.3 mmol, 91%) as a bright yellow solid which was used without further purification. 1HNMR (300 MHz, CDCl3) δ 1.08-2.10 (m, 10H), 2.71-2.84 (m, 1H), 3.79 (s, 3H), 3.89 (s, 3H), 4.00-4.18 (m, 1H), 5.50-5.64 (m, 1H), 5.68 (s, 2H), 6.97 (d, J=2.6 Hz, 1H), 7.07 (dd, J=8.8, 2.6 Hz, 1H), 7.46 (dd, J=8.4, 1.5 Hz, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.78 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 8.10 (br s, 1H), 9.49 (s, 1H). LCMS: m/e 524 (M+H)+, ret time 3.60 min, column B, 4 minute gradient.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]([NH:16]C(=O)OC(C)(C)C)[C:10]1=[O:24].[C:25]([OH:31])([C:27]([F:30])([F:29])[F:28])=[O:26]>C(Cl)Cl>[F:28][C:27]([F:30])([F:29])[C:25]([OH:31])=[O:26].[NH2:16][C@H:11]1[CH2:12][CH2:13][CH2:14][CH2:15][N:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[C:10]1=[O:24]
Reactant: COc1ccccc1N1CCCC[C@H](NC(=O)OC(C)(C)C)C1=O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccccc1N1CCCC[C@H](N)C1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
To a round bottom flask was added (S)-tert-butyl 1-(2-methoxyphenyl)-2-oxoazepan-3-ylcarbamate (27 mg, 0.081 mmol), DCM (1 mL) and TFA (1 mL). The reaction mixture was stirred at rt for 2 hr. The reaction mixture was concentrated under reduced pressure and then dried under high vacuum to give (S)-3-amino-1-(2-methoxyphenyl)azepan-2-one trifluoroacetate (28 mg, 0.080 mmol, 100% yield) as an oil.
Reaction SMILES: Cl.[C:2]([O:6][C:7](=[O:13])[C@H:8]([CH:10]([CH3:12])[CH3:11])[NH2:9])([CH3:5])([CH3:4])[CH3:3].[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.C(N(CC)CC)C>ClCCl>[CH3:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([S:22]([NH:9][CH:8]([CH:10]([CH3:11])[CH3:12])[C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:13])(=[O:24])=[O:23])=[CH:20][CH:21]=1
Reactant: CC(C)[C@H](N)C(=O)OC(C)(C)C
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(S(=O)(=O)NC(C(=O)OC(C)(C)C)C(C)C)cc1

Procedure:
Valine tert-butyl ester hydrochloride is reacted with 4-methoxybenzenesulfonyl chloride in dichloromethane in the presence of triethylamine, to give tert-butyl 2-{[(4-methoxyphenyl)sulfonyl]amino}-3-methylbutanoate.
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:5]=1N)([O-:3])=[O:2].[O:13]=[As]O[As]=O.[OH-].[Na+]>O>[CH3:12][O:11][C:9]1[CH:8]=[CH:7][C:5]([OH:13])=[C:4]([N+:1]([O-:3])=[O:2])[CH:10]=1
Reactant: O=[As]O[As]=O
Reactant: COc1ccc(N)c([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COc1ccc(O)c([N+](=O)[O-])c1

Procedure:
4-Methoxy-2-nitrophenol (9A) was prepared by treating 2-nitro-4-methoxyaniline with arsenic trioxide and sodium hydroxide in water.