Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[F:20][C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[C:24]([OH:26])=O.CCN=C=NCCCN(C)C.Cl.Cl.[C:43]1([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH:48]=[CH:47][C:46]([NH:49][C:50](=[O:60])[CH2:51][C:52](=[O:59])[N:53]2[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)=[CH:45][CH:44]=1>CN(C=O)C.O>[C:43]1([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH:44]=[CH:45][C:46]([NH:49][C:50](=[O:60])[CH2:51][C:52]([N:53]2[CH2:54][CH2:55][N:56]([C:24](=[O:26])[C:23]3[CH:27]=[CH:28][CH:29]=[C:21]([F:20])[CH:22]=3)[CH2:57][CH2:58]2)=[O:59])=[CH:47][CH:48]=1
Reactant: O=C(CC(=O)N1CCNCC1)Nc1ccc(-c2ccccc2)cc1
Reactant: O=C(O)c1cccc(F)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(CC(=O)N1CCN(C(=O)c2cccc(F)c2)CC1)Nc1ccc(-c2ccccc2)cc1
Temperature: 10 °C
Reaction time: 8 h
Yield: 102.1 %

Procedure:
HOBt (34 mg, 0.25 mmol) and DIPEA (67.9 mg, 0.51 mmol) were added to a stirred solution of 3-fluorobenzoic acid (29 mg, 0.21 mmol) in DMF (1.5 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (48 mg, 0.25 mmol) followed by N-biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride (75 mg, 0.2 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water. The resulting precipitate was filtered and dried to afford 91 mg (98%) of N-biphenyl-4-yl-3-[4-(3-fluoro-benzoyl)-piperazin-1-yl]-3-oxo-propionamide. LCMS: 446.18 (M+1)+ 98.1%, 1H NMR: (CDCl3): δ 9.6 (s, 1H), 7.6 (m, 6H), 7.46 (m, 3H), 7.34 (m, 1H), 7.16 (m, 3H), 3.7 (bs, 7H), 3.54 (s, 3H).
Reaction SMILES: [CH3:1][N:2]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:20]=1[NH:19][C:18]([C:21]1[S:22][CH:23]([CH2:26][N:27]3[CH2:32][CH2:31][S:30][CH2:29][CH2:28]3)[CH2:24][N:25]=1)=[CH:17]2)[S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1)(=[O:5])=[O:4].ClC1C=CC=C(C(OO)=[O:41])C=1>ClCCl.C(OCC)(=O)C>[CH3:1][N:2]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:20]=1[NH:19][C:18]([C:21]1[S:22][CH:23]([CH2:26][N:27]3[CH2:32][CH2:31][S:30](=[O:41])[CH2:29][CH2:28]3)[CH2:24][N:25]=1)=[CH:17]2)[S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1)(=[O:5])=[O:4]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CN(c1cccc2cc(C3=NCC(CN4CCSCC4)S3)[nH]c12)S(=O)(=O)c1ccccn1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CN(c1cccc2cc(C3=NCC(CN4CCS(=O)CC4)S3)[nH]c12)S(=O)(=O)c1ccccn1
Reaction time: 3 h
Yield: 21 %

Procedure:
To a solution of N-methyl-N-{2-[5-(thiomorpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl}pyridine-2-sulfonamide (180 mg) in dichloromethane(8 mL) was added m-chloroperbenzoic acid (75 mL) under ice-cooling, and the mixture was stirred for 3 hr under ice-cooling. The reaction solution was diluted with ethyl acetate, washed with aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to basic silica gel column chromatography (ethyl acetate:hexane=6:4-9:1), and the obtained colorless oil was crystallized from ethyl acetate-hexane to give the title compound (39 mg, yield: 21%) as colorless needle crystals. MS:504(MH+). melting point 193-194° C.
Reaction SMILES: [C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[NH2:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1.C(N(CC)CC)C.O>C(Cl)Cl>[CH3:3][C:2]([CH3:5])([CH3:4])[C:1]([NH:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1)=[O:6]
Reactant: Nc1ccncc1
Reactant: CC(C)(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)C(=O)Nc1ccncc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Following procedures generally taught in J. A. Turner, J. Org. Chem. 1983, 48, 3401-3408, a solution of pivaloyl chloride (13.5 mL, 110 mmol) in CH2Cl2 (20 mL) was slowly added to an ice-cold solution of 4-aminopyridine (9.41 g, 100 mmol) and triethylamine (17.4 mL, 125 mmol) in CH2Cl2 (150 mL). After addition was complete, the resulting mixture was warmed to room temperature and stirred for 2 h. The solution was poured into water, the CH2Cl2 layer was washed with dilute NaHCO3, dried over Na2SO4, and evaporated to leave a light brown solid. Recrystallization from EtOAc/hexanes afforded the product as a white crystal, which was collected by vacuum filtration (13.03 g, 73%). 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J=4.8 Hz, 2 H), 7.50 (d, J=4.8 Hz, 2 H), 7.44 (br s, 1 H), 1.33 (s, 9 H). MS (LR-APCI) calcd. for C10H15N2O (M+H) 179.1; found 179.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH3:10])=[CH:5][CH:4]=1.[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])#[N:13].C([O-])(=O)C.[NH4+]>C(OCC)(=O)C.C(O)(=O)C.C1C=CC=CC=1>[CH2:18]([O:17][C:15](=[O:16])[C:14]([C:12]#[N:13])=[C:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH3:10])[CH3:19]
Reactant: COc1ccc(C(C)=O)cc1
Reactant: CCOC(=O)CC#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: c1ccccc1
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C#N)=C(C)c1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 10 h

Procedure:
A mixture of 4′-methoxyacetophenone (50 mmol), ethyl cyanoacetate (50 mmol), acetic acid (1.14 mL) ammonium acetate (400 mg), and benzene (50 mL) is heated to reflux in a Dean-Stark apparatus. After approximately 10 hours, additional ethyl cyanoacetate (50 mmol), acetic acid (1.14 mL), and ammonium acetate (400 mg) are added. After an additional 10 hours, the reaction is cooled to room temperature, diluted with ethyl acetate (30 mL), washed with water (240 mL), brine (40 mL), and dried (Na2SO4). After filtering, the extract is concentrated in vacuo and the desired product, as a mixture of E and Z-isomers, is isolated by column chromatography on silica gel, eluting with 5% ethyl acetate in petroleum ether.
Reaction SMILES: C(OC([CH:11]1[NH:23][CH2:22][C:20]2=[C:21]3[C:16](=[C:17]([C@H:24]4[C@H:28]([C:29]5[C:37]6[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=6)[NH:31][CH:30]=5)[C:27](=[O:38])[NH:26][C:25]4=[O:39])[CH:18]=[CH:19]2)[CH:15]=[CH:14][N:13]3[CH2:12]1)=O)C1C=CC=CC=1.[H][H]>[Pd].CO>[NH:31]1[C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:29]([C@H:28]2[C@H:24]([C:17]3[CH:18]=[CH:19][C:20]4[CH2:22][NH:23][CH2:11][CH2:12][N:13]5[C:21]=4[C:16]=3[CH:15]=[CH:14]5)[C:25](=[O:39])[NH:26][C:27]2=[O:38])=[CH:30]1
Reactant: O=C(OCc1ccccc1)C1Cn2ccc3c([C@@H]4C(=O)NC(=O)[C@H]4c4c[nH]c5ccccc45)ccc(c32)CN1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: O=C1NC(=O)[C@@H](c2ccc3c4c2ccn4CCNC3)[C@@H]1c1c[nH]c2ccccc12

Procedure:
(±)-Trans-7-[4-(1H-indol-3-yl)-2,5-dioxo-pyrrolidin-3-yl]-3,4-dihydro-1H-[1,4]diazepino[6,7,1-hi]indole-2-carboxylic acid benzyl ester (161 mg, 0.31 mmol) and 10% palladium on carbon (100 mg) in anhydrous methanol (15 ml) were stirred under 1 atmosphere of hydrogen for 16 hours. The catalyst was then filtered through a bed of Celite and the filtrate evaporated to dryness to yield (±)-trans-3-(1H-indol-3-yl)-4-(1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-pyrrolidine-2,5-dione as an off white solid (95 mg). 1H NMR (DMSO-d6) 400 MHz δ: 11.04 (d, 1H, J=1.6 Hz), 7.35-7.42 (m, 4H), 7.24 (dd, 1H, J=2.8 and 5.6 Hz), 7.09 (t, 1H, J=7.2 Hz), 6.89-6.98 (m, 3H), 4.52 (dd, 2H, J=7.2 and 24.8 Hz), 4.11 (s, 2H), 4.07-4.10 (m, 2H), 3.14-3.17 (m, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[NH:8][CH:7]=[CH:6][C:5]2=O.[Br:14][C:15]1[C:16]([F:26])=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[CH:19][C:18]2=O.P(Cl)(Cl)([Cl:29])=O>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][CH:6]=[C:5]2[Cl:29].[Br:14][C:15]1[C:16]([F:26])=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[C:18]2[Cl:29]
Reactant: O=c1cc[nH]c2ccc(Br)c(F)c12
Reactant: O=c1cc[nH]c2cc(F)c(Br)cc12
Reactant: O=P(Cl)(Cl)Cl
Product: Fc1c(Br)ccc2nccc(Cl)c12
Product: Fc1cc2nccc(Cl)c2cc1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 50.1 %

Procedure:
A mixture of 6-bromo-7-fluoroquinolin-4(1H)-one/6-bromo-5-fluoroquinolin-4(1H)-one (37.6 g, 155 mmol) and phosphorus oxychloride (101 ml, 1087 mmol) was stirred at RT overnight. The POCl3 was removed via rotovap and the resulting material was dissolved into DCM. This mixture was quenched (very carefully) via pipette addition of sat. aq. Na2CO3. Once the mixture was neutralized, the layers were separated. The aqueous layer was further extracted with DCM. The combined organic layers were concentrated. The resulting material was taken into EtOAc and passed through a short plug of silica gel and concentrated to yield 6-bromo-4-chloro-7-fluoroquinoline/6-bromo-4-chloro-5-fluoroquinoline (40.42 g, 100%) of a brown solid that was a mixture of regioisomers (31:69, by LCMS). MS: m/z: 260.0/262.0 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:16]3=[N:17][S:18](=[O:22])(=[O:21])[CH2:19][CH2:20][N:15]3[CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=1>C1COCC1.CO.[Pt](=O)=O>[CH3:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([CH:11]2[C:16]3=[N:17][S:18](=[O:21])(=[O:22])[CH2:19][CH2:20][N:15]3[CH2:14][CH2:13][CH2:12]2)=[CH:9][CH:10]=1
Reactant: Cc1ccccc1Oc1ccc(C2=CC=CN3CCS(=O)(=O)N=C23)cc1
Agent: O=[Pt]=O
Solvent: CO
Solvent: C1CCOC1
Product: Cc1ccccc1Oc1ccc(C2CCCN3CCS(=O)(=O)N=C23)cc1
Temperature: 50 °C
Reaction time: 8 h
Yield: 50.7 %

Procedure:
Platinum(IV) oxide (30 mg) was added to a solution of 9-[4-(2-methylphenoxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (281 mg) in THF (dry) (150 mL) and MeOH (150 mL) and the mixture was stirred at 50° C. under hydrogen overnight. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). The filtrate was concentrated and the residue was crystallized from MeCN/IPE to give the title compound (144.1 mg) as colorless crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[NH:13][C:14](=[NH:22])[C:15]([F:21])([F:20])[C:16]([F:19])([F:18])[F:17].[H-].[Na+].Cl[C:26]([O:28][CH3:29])=[O:27].O>CN(C)C=O>[CH3:29][O:28][C:26](=[O:27])[NH:22][C:14](=[N:13][C:3]1[C:2]([Cl:1])=[CH:7][C:6]([C:8]([F:10])([F:9])[F:11])=[CH:5][C:4]=1[Cl:12])[C:15]([F:20])([F:21])[C:16]([F:17])([F:18])[F:19]
Reactant: N=C(Nc1c(Cl)cc(C(F)(F)F)cc1Cl)C(F)(F)C(F)(F)F
Reactant: COC(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)NC(=Nc1c(Cl)cc(C(F)(F)F)cc1Cl)C(F)(F)C(F)(F)F
Reaction time: 0.17 h
Yield: 36.9 %

Procedure:
First, 0.18 g (0.50 mmol) of N-(2,6-dichloro-4-trifluoromethylphenyl)-2,2,3,3,3-pentafluoropropionamidine as present compound 4 was dissolved in 10 ml of N,N-dimethylformamide, to which 0.04 g (1.0 mmol) of sodium hydride (about 60% in oil) was added under ice cooling, and the mixture was stirred for 10 minutes. Then, 0.05 g (0.50 mmol) of methyl chloroformate was added to the reaction mixture, which was stirred at room temperature for 6 hours. Water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.08 g of [1-(2,6-dichloro-4-trifluoromethylphenylimino)-2,2,3,3,3-pentafluoropropyl]carbamic acid methyl ester (hereinafter referred to as present compound 60).
Reaction SMILES: [Na+].[C:2]([O:5][CH2:6][C:7]1[CH2:14][S:13][CH:12]2[N:9]([C:10](=[O:29])[CH:11]2[NH:15][C:16](=[O:28])[CH:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:18]2[CH:22]=[CH:21][CH:20]=[CH:19]2)[C:8]=1[C:30]([O-:32])=[O:31])(=[O:4])[CH3:3].Cl[CH2:34][O:35][C:36](=[O:49])[C@H:37]([CH:46]([CH3:48])[CH3:47])[NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>CN(C)C=O.C(OCC)(=O)C>[C:42]([O:41][C:39]([NH:38][CH:37]([CH:46]([CH3:48])[CH3:47])[C:36]([O:35][CH2:34][O:31][C:30]([C:8]1[N:9]2[CH:12]([S:13][CH2:14][C:7]=1[CH2:6][O:5][C:2](=[O:4])[CH3:3])[CH:11]([NH:15][C:16](=[O:28])[CH:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:18]1[CH:19]=[CH:20][CH:21]=[CH:22]1)[C:10]2=[O:29])=[O:32])=[O:49])=[O:40])([CH3:45])([CH3:44])[CH3:43]
Reactant: CCOC(=O)C(C(=O)NC1C(=O)N2C(C(=O)[O-])=C(COC(C)=O)CSC12)n1cccc1
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)OCCl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C(=O)NC1C(=O)N2C(C(=O)OCOC(=O)C(NC(=O)OC(C)(C)C)C(C)C)=C(COC(C)=O)CSC12)n1cccc1
Reaction time: 72 h

Procedure:
A suspension of 5 grams of 3-[(acetyloxy)methyl]-7-[[2-carboethoxy-2-(1-pyrryl)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt and 8.5 grams of N-tert-butoxycarbonyl-L-valine chloromethyl ester, prepared by the general procedure described in W. German Offen. No. 2,236,620 are mixed in 100 ml of dimethylformamide (DMF) and stirred for 72 hours. The mixture is diluted with ethyl acetate, washed with water, aqueous sodium bicarbonate and again with water. The ethyl acetate portion is dried over magnesium sulfate, filtered and evaporated to dryness to give 3-[(acetyloxy)methyl]-7-[[2-carboethoxy-2-(1-pyrryl)acetyl]-amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid N-tert-butoxycarbonyl-2-amino-3-methylbutyryloxymethyl ester from which the protecting group can be removed by standard procedures to give the title compound.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@@H:16]([C:25]([OH:27])=[O:26])[NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28](OCC)C.[N+](=C)=[N-]>C(Cl)(Cl)Cl.C(OCC)(=O)C>[CH3:28][O:26][C:25](=[O:27])[C@H:16]([CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[NH:17][C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Reactant: CCOCC
Agent: C=[N+]=[N-]
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: COC(=O)[C@H](CCCCNC(=O)OCc1ccccc1)NC(=O)OC(C)(C)C

Procedure:
An ethyl solution of 1.48 g (3.9 mmol) of Nε -benzyloxycarbonyl-Nα -(tert-butoxycarbonyl)-L-lysine was combined with an ethyl ether solution of diazomethane at 0° C. The reaction mixture was evaporated to give a colorless oil in nearly quantitative yield (1.54 g). TLC Rf =0.38 (chloroform/ethyl acetate, 5:1). IR (neat) ν 3340, 1710, 1530 cm-1. NMR (CDCl3) δ 7.3 (5H, s), 7.25 (1H, m), 5.05 (2H, s), 5.0 (1H, m), 4.1 (1H, m), 3.8 (3H, s), 3.1 (2H, m), 2.0-1.1 (6H, m), 1.4 (9H, s). The product has the structural formula: ##STR79##
Reaction SMILES: C[O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@:8]([CH3:22])([C@H:9]4[C@@:13]([CH2:15][CH2:16]3)([CH3:14])[C@@H:12]([OH:21])[CH2:11][CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1.CC(C[AlH]CC(C)C)C.C(O)C.Cl>C1(C)C=CC=CC=1.C(O)C.O>[CH3:22][C@@:8]12[CH2:7][CH2:6][C:5]3[CH:4]=[C:3]([OH:2])[CH:20]=[CH:19][C:18]=3[C@H:17]1[CH2:16][CH2:15][C@@:13]1([CH3:14])[C@H:9]2[CH2:10][CH2:11][C@@H:12]1[OH:21]
Reactant: COc1ccc2c(c1)CC[C@@]1(C)[C@@H]3CC[C@H](O)[C@@]3(C)CC[C@H]21
Agent: CC(C)C[AlH]CC(C)C
Agent: Cl
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: C[C@@]12CCc3cc(O)ccc3[C@H]1CC[C@@]1(C)[C@H]2CC[C@@H]1O
Temperature: 0 °C
Reaction time: 3.5 h
Yield: 99.2 %

Procedure:
74 mg of 3-methoxy-8β-methyl-estra-1,3,5(10)-trien-17β-ol was dissolved in 3 ml of anhydrous toluene, cooled to 0° C. and mixed carefully under argon with 0.6 ml of DIBAH. The reaction mixture was slowly refluxed, and it was kept at this temperature for 3.5 hours. Then, it was cooled again to 0° C., the solution was mixed in succession with 2 ml of ethanol, 2 ml of ethanol-water mixture (v/v=1/1) and 2 ml of semi-concentrated hydrochloric acid and extracted several times with ethyl acetate. The collected organic phases were washed neutral with water, dried with magnesium sulfate and evaporated to the dry state in a vacuum. 70 mg (99%) of colorless crystals with a melting point of 168-170° C. was obtained.
Reaction SMILES: O([C:8]([NH:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][N:16]2[C:22](=[O:23])[C@H:21]3[CH2:24][CH2:25][CH2:26][C@H:20]3[NH:19][C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]2=3)=[CH:13][CH:12]=1)=[O:9])C1C=CC=CC=1.[CH2:33](CN)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH3:42][N:43](C=O)C>C(OCC)(=O)C>[CH2:33]([N:43]([CH3:42])[C:8](=[O:9])[NH:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][N:16]2[C:22](=[O:23])[C@H:21]3[CH2:24][CH2:25][CH2:26][C@H:20]3[NH:19][C:18]3[CH:27]=[CH:28][CH:29]=[CH:30][C:17]2=3)=[CH:13][CH:12]=1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: O=C(Nc1ccc(CN2C(=O)[C@H]3CCC[C@H]3Nc3ccccc32)cc1)Oc1ccccc1
Reactant: CN(C)C=O
Reactant: NCCc1ccccc1
Solvent: CCOC(C)=O
Product: CN(Cc1ccccc1)C(=O)Nc1ccc(CN2C(=O)[C@H]3CCC[C@H]3Nc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 84 h
Yield: 66 %

Procedure:
To a solution of (3aR*,10aS*)-9-[4-(phenoxycarbonylamino)benzyl]-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one (0.43 g, 1 mmol) in DMF (5 mL) was added N-benzylmethylamine (0.14 mL, 1.1 mmol) and the mixture was stirred at room temperature for 84 hours. This reaction mixture was diluted with ethyl acetate and washed with 2 portions of water and, then, with saturated aqueous NaCl solution. This solution was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate=1:1) to provide 0.30 g (yield 66%) of the title compound. Amorphous.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][CH2:10][OH:11].[CH:12]1([CH2:18][C:19](O)=[O:20])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.C(Cl)(Cl)Cl>[CH:12]1([CH2:18][C:19]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:8][CH2:9][CH2:10][OH:11])=[O:20])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: Nc1ccccc1CCCO
Reactant: O=C(O)CC1CCCCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: O=C(CC1CCCCC1)Nc1ccccc1CCCO
Temperature: 25 °C
Reaction time: 113 h
Yield: 51.9 %

Procedure:
To a solution of 3-(2-aminophenyl)propan-1-ol (180 mg) and cyclohexylacetic acid (203 mg) in dichioromethane (12mL) were added 1-hydroxybenzotriazole (193 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (274 mg) under ice cooling. The solution was stirred at room temperature for 113 hours. Chloroform was then added to the solution and it was washed in turn with water and saturated aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, hexane: ethyl acetate=1:1) to give the title compound (170 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[CH2:10][CH2:9][C:8]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH3:30])[CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[CH:18][CH:17]=3)=[O:14])=[CH:7][C:6]=2[CH:31]=1.C(=O)([O-])[O-].[K+].[K+].C(O[CH2:42][CH3:43])(=O)C>O.C(O)C.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>[CH2:10]([N:11]([CH2:42][CH3:43])[C:5]1[CH:6]=[CH:31][C:2]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH3:12])[CH2:10][CH2:9][C:8]([C:13]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH3:30])[CH:24]5[CH2:25][CH2:26][O:27][CH2:28][CH2:29]5)=[CH:18][CH:17]=4)=[O:14])=[CH:7][C:6]=3[CH:31]=2)=[CH:3][CH:4]=1)[CH3:9]
Reactant: CN1CCC(C(=O)Nc2ccc(CN(C)C3CCOCC3)cc2)=Cc2cc(Br)ccc21
Reactant: CCOC(C)=O
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: CCN(CC)c1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 33 %

Procedure:
In water:ethanol:toluene (1:1:10, v/v, 18.0 ml) were dissolved (4-diethylamino)phenyl borate (234 mg) and 7-bromo-1-methyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (391 mg). To the solution was added potassium carbonate (268 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (37 mg), and the mixture was heated to reflux under argon atmosphere for 10 hours. The mixture was diluted with ethyl acetate, and washed with water and saturated brine, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (45 g, ethyl acetate:ethanol=20:1) and recrystallized from ethanol to give 7-(4-diethylaminophenyl)-1-methyl-N-(4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (145 mg, 33%) as yellow crystals.
Reaction SMILES: [NH:1]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:2]([C:20](O)=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10].CCN(C(C)C)C(C)C.[NH2:39][CH2:40][C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42].Cl.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[NH:1]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:2]([C:20]([NH:39][CH2:40][C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42])=[O:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10]
Reactant: NCC(=O)OCc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)NC(=N)NCCC[C@@H](NC(=O)OC(C)(C)C)C(=O)O)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(S(=O)(=O)NC(=N)NCCC[C@@H](NC(=O)OC(C)(C)C)C(=O)NCC(=O)OCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 4 h
Yield: 83.1 %

Procedure:
To a suspension of Boc—(D)—Arg(Tos)—OH (1 g, 2.34 mmol) in CH2Cl2 (10 mL) was added DIEA (1 mL) at 0° C. To the clear solution was added Gly—OBn.HCl (0.52 g, 2.58 mmol) and BOP (1.2 g, 2.8 mmol). The solution was stirred for 4 h at 0° C. Solvents were evaporated and residue was dissolved in a mixture of EtOAc (100 mL) and water (20 mL). The organic layer was washed with sat. NaHCO3 (10 mL), water (10 mL), 1 N HCl (10 mL) and sat. NaCl (3×10 mL), dried with MgSO4, filtered and evaporated. The solid residue was purified by column chromatography on silica gel (EtOAc) to give 1.12 g of the title compound as a powder. ES—MS (M+H)+=576.3