Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17]([OH:19])=O)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:26])[C:5]=2[NH:4][N:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH:49]1[CH2:54][CH2:53][CH:52]([N:55]2[CH2:61][CH2:60][C:59]3[CH:62]=[CH:63][CH:64]=[CH:65][C:58]=3[NH:57][C:56]2=[O:66])[CH2:51][CH2:50]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:19])[N:49]4[CH2:50][CH2:51][CH:52]([N:55]5[CH2:61][CH2:60][C:59]6[CH:62]=[CH:63][CH:64]=[CH:65][C:58]=6[NH:57][C:56]5=[O:66])[CH2:53][CH2:54]4)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:26])[C:5]=2[NH:4][N:3]=1
Reactant: O=C(O)C[C@@H]1Cc2cc(Cl)c3[nH]nc(Cl)c3c2CN(CC(F)(F)F)C1=O
Reactant: O=C1Nc2ccccc2CCN1C1CCNCC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(C[C@@H]1Cc2cc(Cl)c3[nH]nc(Cl)c3c2CN(CC(F)(F)F)C1=O)N1CCC(N2CCc3ccccc3NC2=O)CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 59 %

Procedure:
(S)-2-(1,4-Dichloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino [3,4-e]indazol-7-yl)acetic acid(95 mg, 0.232 mmol) was dissolved in N,N-dimethylformamide (2.0 ml). TBTU (79 mg, 0.246 mmol) was added to the mixture followed by 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one (72 mg, 0.293 mmol) and then N,N-diisopropylethylamine (150 μl, 0.861 mmol). Reaction stirred at room temperature for 4 hours. Reaction was quenched with 50% acetonitrile-water. Material was purified by reverse phase prep HPLC (water-acetonitrile-trifluoroacetic acid). Acetonitrile was removed from the fractions by roto-vap. Remaining aqueous was made basic with aqueous sodium bicarbonate. Material was extracted twice with ethyl acetate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as white solid in 59% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.88 (s, 1H) 8.49 (s, 1 H) 7.35 (s, 1H) 7.00-7.09 (m, 3H) 6.70-6.87 (m, 1H) 5.42 (s, 2H) 4.49 (d, J=12.51 Hz, 1H) 4.36-4.45 (m, 1H) 4.25-4.36 (m, 1H) 4.11-4.24 (m, 1H) 3.91-4.10 (m, 2H) 3.34-3.41 (m, 2H) 3.19 (d, J=18.01 Hz, 1H) 3.05-3.15 (m, 1H) 2.93-3.03 (m, 1H) 2.83-2.93 (m, 3H) 2.53-2.65 (m, 1H) 2.32-2.47 (m, 1H) 1.57-1.87 (m, 3H) 1.44-1.57 (m, 1H). High resolution MS m/e (M+H)−=637.1735.
Reaction SMILES: [Br:1][C:2]1[CH:20]=[C:19]2[C:5]([C:6](=[O:22])[C:7](=[O:21])[C:8]3[S:18][CH2:17][C:11]4([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]4)[O:10][C:9]=32)=[CH:4][CH:3]=1.[CH2:23]([C@@H:30]1[CH2:32][O:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[Br:1][C:2]1[CH:20]=[C:19]2[C:5]([C:6](=[O:22])[C:7](=[O:21])[C:8]3[S:18][CH2:17][C:11]4([CH2:16][CH2:15][N:14]([CH2:32][C@H:30]([OH:31])[CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:13][CH2:12]4)[O:10][C:9]=32)=[CH:4][CH:3]=1
Reactant: O=C1C(=O)c2ccc(Br)cc2C2=C1SCC1(CCNCC1)O2
Reactant: c1ccc(C[C@@H]2CO2)cc1
Product: O=C1C(=O)c2ccc(Br)cc2C2=C1SCC1(CCN(C[C@H](O)Cc3ccccc3)CC1)O2

Procedure:
Compound 222 was synthesized using 9-bromospiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione, (2R)-2-benzyloxirane and conditions outlined in procedure Y. M.p.=82-84° C., (DMSO-d6) δ: 7.88-7.72 (m, 3H), 7.3-7.1 (m, 5H), 4.46-4.4 (m, 1H), 3.9-3.8 (m, 1H), 3.08 (s, 2H), 2.82-2.67 (m, 3H), 2.63-2.55 (m, 1H), 2.4-2.25 (m, 4H), 2.06-1.93 (m, 2H), 1.9-1.78 (m, 2H); LCMS=514 [M+H].
Reaction SMILES: [NH:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[C:21]([CH3:22])=[CH:20][C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:23]C)[CH:18]=4)[N:13]=3)=[CH:8][CH:7]=2)=[N:4][N:3]=[N:2]1>CN1C(=O)CCC1>[NH:4]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[C:21]([CH3:22])=[CH:20][C:19]4[C:14](=[CH:15][CH:16]=[C:17]([OH:23])[CH:18]=4)[N:13]=3)=[CH:8][CH:7]=2)=[N:1][N:2]=[N:3]1
Reactant: COc1ccc2nc(-c3ccc(-c4nnn[nH]4)cc3)c(C)cc2c1
Solvent: CN1CCCC1=O
Product: Cc1cc2cc(O)ccc2nc1-c1ccc(-c2nnn[nH]2)cc1
Temperature: 140 °C
Reaction time: 4 h
Yield: 38.1 %

Procedure:
2-(4-(1H-tetrazol-5-yl)phenyl)-6-methoxy-3-methylquinoline (128 mg, 0.40 mmol) was dissolved in 5 mL of NMP and Na2S (47 mg, 0.60 mmol) was added to it. The mixture was then stirred for 4 hours at 140° C. in a microwave reactor. After concentration in vacuo the crude was dissolved in 5 mL of 1N NaOH and slowly acidified with 1N HCl to a pH of 4. The solids were filtered and dried in vacuo to afford 46.2 mg (38% yield) of Compound 2. 1H NMR (DMSO-d6, 400 MHz): δ 10.10-10.00 (bs, 1H), 8.18-8.15 (d, 2H), 8.08 (s, 1H), 7.87-7.84 (m, 3H), 7.30-7.26 (d, 1H), 7.13 (s, 1H), 2.45 (s, 3H). MS (ESI): m/z 304.11 [M+H]+.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:5]([CH3:9])[CH:6]=[CH:7][CH:8]=1.[C:10]1([CH3:20])[CH:15]=[CH:14][C:13]([S:16](Cl)(=[O:18])=[O:17])=[CH:12][CH:11]=1>>[C:10]1([CH3:20])[CH:15]=[CH:14][C:13]([S:16]([NH:1][CH2:2][CH2:3][C:4]2[N:5]([CH3:9])[CH:6]=[CH:7][CH:8]=2)(=[O:18])=[O:17])=[CH:12][CH:11]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Cn1cccc1CCN
Product: Cc1ccc(S(=O)(=O)NCCc2cccn2C)cc1

Procedure:
Prepared from 2-(2-aminoethyl)-1-methylpyrrole and p-toluenesulphonylchloride analogously to Example A.
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2N=NN(CC)C=2N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:42][C:38]3([CH2:41][O:40][CH2:39]3)[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].Cl[CH2:44][C:45]1[O:46][C:47]([CH3:50])=[N:48][N:49]=1>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:37][C:38]3([CH2:39][O:40][CH2:41]3)[CH2:42]2)[C:30]2[N:35]=[N:34][N:33]([CH2:44][C:45]3[O:46][C:47]([CH3:50])=[N:48][N:49]=3)[C:31]=2[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: Cc1nnc(CCl)o1
Reactant: CC(C)(C)c1nc(N2CC3(COC3)C2)c2nn[nH]c2n1
Agent: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Product: Cc1nnc(Cn2nnc3c(N4CC5(COC5)C4)nc(C(C)(C)C)nc32)o1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-Butyl-7-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 2-(chloromethyl)-5-methyl-1,3,4-oxadiazole and isolated as white solid. MS (m/e): 371.2 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[CH2:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:8]=[C:7](Cl)[CH:6]=1.[F:23][C:24]([F:39])([F:38])[C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.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>[CH3:1][O:2][C:3](=[O:22])[CH2:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:8]=[C:7]([C:27]2[CH:28]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:30]=[C:25]([C:24]([F:23])([F:39])[F:38])[CH:26]=2)[CH:6]=1
Reactant: OB(O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: COC(=O)Cc1cc(Cl)nc(-c2ccc(C(F)(F)F)cc2)c1
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: COC(=O)Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c1
Temperature: 85 °C
Yield: 59.1 %

Procedure:
To a degassed solution of [2-chloro-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester (165 mg, 0.5 mmol), 3,5-di(trifluoromethyl)benzeneboronic acid (160 mg, 0.6 mmol), 2N Na2CO3 (1.0 mL) in DME (9 mL) was added tetrakis(triphenylphosphine)palladium (70 mg, 0.06 mmol) under argon. The mixture was heated to 85° C. for 6 h, cooled to room temperature, diluted with water, and extracted with methylene chloride (3×). The organic solution was washed with brine, dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel (0-20% ethyl acetate in methylene chloride) to give the product as a white solid (150 mg, 59%). 1H NMR (300 MHz, CDCl3) δ 8.57 (s, 2H), 8.24 (d, J=8.29 Hz, 2H), 7.96 (s, 1H), 7.73-7.85 (m, 4H), 3.83 (s, 2H), 3.78 (s, 3H). MS m/e 508.2 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][S:8][C@H:9]2[CH2:13][N:12]([S:14]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)(=[O:16])=[O:15])[C@H:11]([C:25]([OH:27])=O)[CH2:10]2)=[CH:5][CH:4]=1.[CH2:30](CN)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C[CH2:40][N:41]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.OS([O-])(=O)=O.[K+].CCOC(C)=O>C1COCC1>[CH2:30]([N:41]([CH3:40])[C:25]([C@@H:11]1[CH2:10][C@@H:9]([S:8][CH2:7][C:6]2[CH:28]=[CH:29][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:13][N:12]1[S:14]([CH2:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)(=[O:15])=[O:16])=[O:27])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: NCCc1ccccc1
Reactant: CCN=C=NCCCN(C)C
Reactant: COc1ccc(CS[C@@H]2C[C@@H](C(=O)O)N(S(=O)(=O)CCc3ccccc3)C2)cc1
Agent: O=S(=O)([O-])O
Agent: On1nnc2ccccc21
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1ccc(CS[C@@H]2C[C@@H](C(=O)N(C)Cc3ccccc3)N(S(=O)(=O)CCc3ccccc3)C2)cc1
Temperature: 25 °C
Yield: 9.7 %

Procedure:
A solution of 242 mg (0.4 mmol) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(2-phenyl-ethanesulfonyl)-pyrrolidine-2-carboxylic acid in 4 ml THF was treated at 0° C. with 0.057 ml (0.44 mmol) N-benzylmethylamine, 92 mg (0.48 mmol) EDCI , 6.1 mg (0.04 mmol) HOBT and warmed up over night to RT. The reaction was poured into aqueous 10% KHSO4/EtOAc (3×). The organic phases were washed with aqueous 10% NaCl solution and dried over Na2SO4 to give after flash silicagel column (Hexane/EtOAc 4:1) 21 mg (10%) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(2-phenyl-ethanesulfonyl)-pyrrolidine-2-carboxylic acid benzyl-methyl-amide, MS: 539 (MH+).
Reaction SMILES: N1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:7][C:8]([F:21])([F:20])[S:9]([O:12]S(C(F)(F)F)(=O)=O)(=[O:11])=[O:10].Cl.[OH2:23]>CCOC(C)=O>[CH2:3]([C:4]([C:4]1[CH:3]=[C:2]2[C:2]([CH:3]=[CH:4][C:5]([O:12][S:9]([C:8]([F:21])([F:20])[F:7])(=[O:11])=[O:10])=[CH:6]2)=[CH:6][CH:5]=1)([OH:23])[CH2:5][CH3:6])[CH3:2]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: O
Reactant: c1ccncc1
Agent: Cl
Solvent: CCOC(C)=O
Product: CCC(O)(CC)c1ccc2ccc(OS(=O)(=O)C(F)(F)F)cc2c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 66 %

Procedure:
Cool a CH2CL2 (30 mL) solution of 7-(1-ethyl-11-hydroxypropyl)naphthalen-2-ol (0.97 g, 4.2 mmol) and pyridine (1.3 mL, 16.3 mmol) with an ice bath. Treat the cooled solution dropwise with trifluoromethanesulfonic anhydride (1.0 mL, 6.1 mmol). Remove the cooling bath and stir the mixture for 1.5 h at RT. Quench the reaction with ice water. Dilute the reaction mixture with EtOAc and water (100 mL each) and acidify to pH 1 using 0.1N HCl. Dry the organic layer over Na2SO4, filter and concentrate the filtrate. Purify by radial silica gel (2:98 to 10:90 EtOAc:hex) to give the title compound as a colorless oil (1.46 g, 66%). MS (ES) m/e 377 (M-NH4).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[NH:11][C:12]1[N:17]=[C:16]([C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH:15]=[CH:14][N:13]=1.[NH2:23][C:24]1[S:25][C:26]([CH3:29])=[CH:27][N:28]=1.N1C=CC=C(C2C=CN=C(NC3C=CC(C(O)=O)=CC=3)N=2)C=1.CC1N=CN(C2C=C(N)C=C(C(F)(F)F)C=2)C=1>>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:23][C:24]2[S:25][C:26]([CH3:29])=[CH:27][N:28]=2)=[O:8])=[CH:4][C:3]=1[NH:11][C:12]1[N:17]=[C:16]([C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH:15]=[CH:14][N:13]=1
Reactant: Cc1ccc(C(=O)O)cc1Nc1nccc(-c2nccs2)n1
Reactant: Cc1cnc(N)s1
Agent: Cc1cn(-c2cc(N)cc(C(F)(F)F)c2)cn1
Agent: O=C(O)c1ccc(Nc2nccc(-c3cccnc3)n2)cc1
Product: Cc1cnc(NC(=O)c2ccc(C)c(Nc3nccc(-c4nccs4)n3)c2)s1

Procedure:
4-methyl-3-(4-thiazol-2-yl-pyrimidin-2-ylamino)-benzoic acid and 2-amino-5-methylthiazole were used instead of 4-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzoic acid and 3-(4-methylimidazol-1-yl)-5-trifluoromethyl-phenylamine according to the similar procedure to Example 5 to give the titled compound as yellow brown solid.
Reaction SMILES: [N:1]1C=CC=C[CH:2]=1.[N:7]1([C:13]2[N:18]=[C:17]([CH2:19][C:20](=[O:36])[N:21]3[C:29]4[C:24](=[C:25](C5C=CN=CC=5)[CH:26]=[CH:27][CH:28]=4)[CH2:23][CH2:22]3)[NH:16][C:15](=[O:37])[CH:14]=2)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.Cl.[CH3:39][N:40]([CH3:49])[CH2:41][CH2:42]CN=C=NCC.N1(C2N=C(CC([O-])=O)NC(=O)C=2)CCOCC1.[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[CH3:49][N:40]1[CH2:39][CH2:2][N:1]([C:25]2[CH:26]=[CH:27][CH:28]=[C:29]3[C:24]=2[CH2:23][CH2:22][N:21]3[C:20](=[O:36])[CH2:19][C:17]2[NH:16][C:15](=[O:37])[CH:14]=[C:13]([N:7]3[CH2:8][CH2:9][O:10][CH2:11][CH2:12]3)[N:18]=2)[CH2:42][CH2:41]1
Reactant: c1ccncc1
Reactant: O=C(Cc1nc(N2CCOCC2)cc(=O)[nH]1)N1CCc2c(-c3ccncc3)cccc21
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN1CCN(c2cccc3c2CCN3C(=O)Cc2nc(N3CCOCC3)cc(=O)[nH]2)CC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
8 ml of pyridine, 160 mg of 4-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indole (reference example 10d) and 212 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are successively added to a solution of 288 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (example 1d, step 2d) in 8 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 48 hours. After the addition of 50 ml of water and extraction with ethyl acetate, the organic phases are combined and then dried over magnesium sulfate, filtered through sintered glass, and concentrated under reduced pressure. After purification of the residue by silica column chromatography, elution being carried out with a mixture of dichloromethane and 7N ammoniacal methanol (90/10), 29 mg of 2-{2-[4-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of a white-pink powder, the characteristics of which are the following:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=O)=[CH:4][CH:3]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1>O>[Cl-:17].[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S+:8]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(S(=O)c2ccc(C)cc2)cc1
Reactant: Cc1ccc(Cl)cc1
Solvent: O
Product: Cc1ccc([S+](c2ccc(C)cc2)c2ccc(C)cc2)cc1
Product: [Cl-]

Procedure:
The target compound was obtained by following the procedure of Synthesis Example 1 aside from using bis(4-methylphenyl)sulfoxide instead of the diphenyl sulfoxide and 4-chlorotoluene instead of the chlorobenzene in Synthesis Example 1, and increasing the amount of water for extraction.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([NH2:14])[C:10]([F:13])([F:12])[F:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:15](Cl)(=[O:26])[O:16][C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1.N1C=CC=CC=1.O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([NH:14][C:15](=[O:26])[O:16][C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)[C:10]([F:11])([F:12])[F:13])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: NC(c1ccc(Cl)c(Cl)c1)C(F)(F)F
Solvent: c1ccncc1
Solvent: O
Solvent: ClCCl
Product: O=C(NC(c1ccc(Cl)c(Cl)c1)C(F)(F)F)Oc1ccc([N+](=O)[O-])cc1
Yield: 92.1 %

Procedure:
A solution of 148 (1.00 g, 4.01 mmol), 4-nitrophenyl carbonochloridate (0.9085 g, 4.507 mmol) and pyridine (0.7131 g, 9.015 mmol) in DCM (10 mL) were stirred for 30 min. Water was added and the reaction mixture was extracted with DCM. The organic layer was concentrated and purified by SiO2 chromatography eluting with 20% EtOAc/hexane to afford 1.511 g (90.0%) of 4-nitrophenyl 1-(3,4-dichlorophenyl)-2,2,2-trifluoroethylcarbamate (150).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:12][C:11](C=O)=[CH:10][C:9]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C1C=C(Cl)C=C(C(OO)=[O:36])C=1.[OH-].[K+]>C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:12][C:11]([OH:36])=[CH:10][C:9]=1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: COCCOCOc1c(-c2ccccc2)cc(C=O)cc1-c1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Product: COCCOCOc1c(-c2ccccc2)cc(O)cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 60.5 %

Procedure:
To a stirred solution of 2′-methoxyethoxymethoxy-[1,1′;3′,1″]terphenyl-5′-carboxaldehyde (0.836 g, 2.31 mmol) in CH2Cl2 (25 mL) at room temperature was added MCPBA (0.598 g, 3.46 mmol). The reaction mixture was refluxed for 48 h. After concentration, the residue was dissolved in EtOAc (300 mL). The organic layer 15 was washed with sat. aq. NaHCO3 until effervescence ceased followed brine (30 mL) and then dried (Na2SO4). After concentration, the residue was dissolved in THF:MeOH (3:2, 45 mL) followed by the dropwise addition of 1 N KOH (11.6 mL, 11.6 mmol). The reaction mixture was stirred at room temperature for 1.5 h and then concentrated. The residue was diluted with H2O (30 mL) and then acidified to pH 4 with 1 N HCl followed by extraction with EtOAc (300 mL). This organic layer was washed with brine (30 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (5 to 15% acetone/hexane gradient) to afford the product (0.490 g, 61%) as a solid; 1H NMR (CDCl3) δ 2.73-2.86 (m, 2H), 2.90-2.98 (m, 2H), 3.17 (s, 3H), 4.35 (s, 2H), 4.67 (s, 1H), 6.82 (s, 2H), 7.27-7.47 (m, 6H), 7.57 (d, J=9.3 Hz, 4H); mass spectrum [(+) ESI], m/z 373 (M+Na)+.
Reaction SMILES: [CH3:1][NH:2][C:3]([NH:5][CH2:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])=S.[N:17]#[C:18][NH2:19].[Pb]>>[C:18]([NH:19][C:3]([NH:2][CH3:1])=[N:5][CH2:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])#[N:17]
Reactant: N#CN
Reactant: CNC(=S)NCCCSCc1[nH]cnc1C
Agent: [Pb]
Product: CNC(=NCCCSCc1[nH]cnc1C)NC#N
Yield: 15 %

Procedure:
The reaction of N-methyl-N'-[3-((4-methyl-5-imidazolyl)methylthio)propyl]thiourea (5.9 g.) with lead cyanamide (17.5 g.) by a procedure similar to that described in Example 3(b) afforded N-cyano-N'-methyl-N"-[3-((4-methyl-5-imidazolyl)methylthio)propyl]guanidine (0.91 g.), m.p. 156°-158°, following chromatography on silica gel with successive elution by chloroformethyl acetate (1:1), ethyl acetate and ethyl acetate isopropyl alcohol (5:1) and final recrystallisation from isopropyl alcohol-ether.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:30][CH:31]([CH2:34][CH2:35][CH3:36])[CH:32]=O.[H-].[Na+]>C(#N)C.O>[CH3:30][CH:31]([CH2:34][CH2:35][CH3:36])[CH:32]=[CH:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: CCOC(=O)CCCCBr
Reactant: CCCC(C)C=O
Agent: [H-]
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CC#N
Product: CCCC(C)C=CCCCC(=O)OCC
Yield: 54 %

Procedure:
104.54 g (0.5 mol) of ethyl 5-bromovalerate and 137.5 g (0.525 mol) of triphenyl phosphine were refluxed for 36 hours in 1 l of acetonitrile. After the reaction terminated, 500 ml of acetonitrile was distilled off, then the reaction mixture was dried. Under nitrogen atmosphere, 50.1 g (0.5 mol) of 2-methyl valeraldehyde was added, then the reaction mixture was stirred. Controlling the reaction temperature to within the range of 25°-35° C., 20.0 g (0.5 mol) of oily (60%) sodium hydride was added little by little. After the addition, the reaction mixture was stirred over night at room temperature. After the reaction ended, 250 g of water was added into the reaction mixture, then oil layer was separated and the water layer was extracted three times with 150 ml of hexane. The organic layers were combined and washed with 150 ml of water. After the hexane solution was dried sufficiently with anhydrous Magnesium sulfate, solvent was removed under reduced pressure, and distilled to obtain 57.3 g of ethyl 7-methyl-5-decenoate (Yield: 54%, based upon starting material). The product was gradually added dropwise into 500 ml of dried ethylether solution including 5.12 g (0.135 mol) of aluminum lithium hydride under nitrogen stream. The dropwise addition was done while a reaction vessel was cooled sufficiently by ice water. After the addition was completed, the reaction temperature was returned to room temperature and stirred for 2 hours. Then, 300 ml of water was added gradually into the reaction mixture, and the organic layer was separated. The water layer was returned to pH7 and extracted three times with 100 ml of diethylether. The organic layers were combined and washed with 100 ml of water, and solvent was removed from the reaction mixture under reduced pressure to obtain 44.2g of 7-methyl-5-decen-1-ol (Yield: 52", based upon starting material).
Reaction SMILES: [OH:1][CH2:2][C:3]1[N:4]=[C:5]([CH:8]([CH3:10])[CH3:9])[S:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>ClCCl>[CH:8]([C:5]1[S:6][CH:7]=[C:3]([CH2:2][O:1][S:21]([CH3:20])(=[O:23])=[O:22])[N:4]=1)([CH3:10])[CH3:9]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)c1nc(CO)cs1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)c1nc(COS(C)(=O)=O)cs1
Reaction time: 1 h

Procedure:
A solution of 1.2 mmol of 4-(hydroxymethyl)-2-isopropylthiazole and 1.3 mmol of diisopropylethylamine in 20 ml of dichloromethane was cooled to -20° C. and treated dropwise with 1.3 mmol of methanesulfonyl chloride. The resulting mixture was stirred for 1 h, quenched with aqueous citric acid, separated, dried over Na2SO4, and concentrated in vacuo to provide the desired compound.
Reaction SMILES: [F:1][C:2]1[C:7]2[C:8](=[O:13])O[C:10](=[O:12])[NH:11][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14].[NH:15]1[CH2:22][CH2:21][CH2:20][C@H:16]1C(O)=O>CN(C)C=O.C(O)(=O)C>[F:1][C:2]1[C:7]2[C:8](=[O:13])[N:15]3[CH2:22][CH2:21][CH2:20][C@H:16]3[C:10](=[O:12])[NH:11][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14]
Reactant: O=c1[nH]c2ccc(F)c(F)c2c(=O)o1
Reactant: O=C(O)[C@@H]1CCCN1
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: O=C1Nc2ccc(F)c(F)c2C(=O)N2CCC[C@@H]12
Yield: 82.3 %

Procedure:
A solution of 28.8 g (144.6 mmol) of 5,6-difluoro-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione and 16.7 g (144.6 mmol) of L-proline in 110 ml of dimethylformamide and 20 ml of acetic acid was stirred at 120° for 16 hours. The brown solution was evaporated and the brown residue obtained was crystallized from ethanol. There were obtained 30 g (82%) of (S)-6,7-difluoro-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione as colourless crystals of m.p. >250°.