Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]([F:19])=[CH:10][C:9]=1[NH:20][C:21](=[O:44])[CH2:22][C:23](=O)[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([N:30]2[C:34]([CH2:35][O:36]C3CCCCO3)=[CH:33][N:32]=[N:31]2)[CH:25]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:19][C:11]1[C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:13][C:8]2[N:7]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([N:30]4[C:34]([CH2:35][OH:36])=[CH:33][N:32]=[N:31]4)[CH:25]=3)[CH2:22][C:21](=[O:44])[NH:20][C:9]=2[CH:10]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(N2CCCC2)c(F)cc1NC(=O)CC(=O)c1cccc(-n2nncc2COC2CCCCO2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1CC(c2cccc(-n3nncc3CO)c2)=Nc2cc(N3CCCC3)c(F)cc2N1

Procedure:
The title compound was prepared from (RS)-[4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phenyl}-propionylamino)-5-pyrrolidin-1-yl-phenyl]-carbamic acid tert.-butyl ester (Example M49) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (72 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.[N:18]1([C:24]2[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][C:25]=2[C:26](Cl)=[O:27])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][N:15]([C:26]([C:25]2[CH:29]=[C:30]([N+:33]([O-:35])=[O:34])[CH:31]=[CH:32][C:24]=2[N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:27])[CH2:14][CH2:13]1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])ccc1N1CCOCC1
Reactant: FC(F)(F)c1ccc(N2CCNCC2)c(Cl)c1
Product: O=C(c1cc([N+](=O)[O-])ccc1N1CCOCC1)N1CCN(c2ccc(C(F)(F)F)cc2Cl)CC1

Procedure:
The title compound was prepared according to the procedure described for example 46 from 1-(2-Chloro-4-trifluoromethyl-phenyl)-piperazine and 2-Morpholin-4-yl-5-nitro-benzoyl chloride (74%, yellow solid, MS (m/e): 499.2 (M+H, 100%)
Reaction SMILES: [BH4-].[Na+].[CH:3]([C:5]1[CH:6]=[CH:7][C:8]2[N:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:29]=[CH:28][C:27]([N:30]5[C:42]6[CH:41]=[CH:40][C:39]([CH:43]=[O:44])=[CH:38][C:37]=6[C:36]6[C:31]5=[CH:32][CH:33]=[CH:34][CH:35]=6)=[CH:26][CH:25]=4)=[CH:20][CH:19]=3)[C:10]3[C:15]([C:16]=2[CH:17]=1)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[O:4].O.Cl>C1COCC1>[OH:44][CH2:43][C:39]1[CH:40]=[CH:41][C:42]2[N:30]([C:27]3[CH:28]=[CH:29][C:24]([C:21]4[CH:20]=[CH:19][C:18]([N:9]5[C:8]6[CH:7]=[CH:6][C:5]([CH2:3][OH:4])=[CH:17][C:16]=6[C:15]6[C:10]5=[CH:11][CH:12]=[CH:13][CH:14]=6)=[CH:23][CH:22]=4)=[CH:25][CH:26]=3)[C:31]3[C:36]([C:37]=2[CH:38]=1)=[CH:35][CH:34]=[CH:33][CH:32]=3
Reactant: O=Cc1ccc2c(c1)c1ccccc1n2-c1ccc(-c2ccc(-n3c4ccccc4c4cc(C=O)ccc43)cc2)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: OCc1ccc2c(c1)c1ccccc1n2-c1ccc(-c2ccc(-n3c4ccccc4c4cc(CO)ccc43)cc2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 93.4 %

Procedure:
Sodium borohydride (2.40 g, 63.4 mmol)) was added to the 4,4′-bis(3-formyl-carbazol-9-yl)biphenyl (2) (3.42 g, 6.33 mmol) in THF (1.2 L) and the resulting suspension was stirred at room temperature for 24 h. Once the reaction was complete, the mixture was slowly poured into water (400 ml) and the mixture was left to stir at room temperature for a further 30 min. The reaction mixture was acidified to pH 6 with hydrochloric acid (5M) and the product was extracted with dichloromethane (3×300 ml). The combined organic phase was washed with water (400 ml) and brine (400 ml), dried (MgSO4), filtered and the filtrate evaporated to dryness. The crude product was purified by chromatography on silica using 50% THF/toluene as the eluent The product, 4,4′-bis(3-(hydroxymethyl)carbazol-9-yl)(3) was obtained as a pale yellow solid (3.22 g, 94%) with m.p. 268° C. (dec). 1H n.m.r.: (300 MHz, CDCl3): δ 8.23 (2H, d, J 7.61 Hz, aromatic H); 8.18 (2H, s, aromatic H); 8.06 (4H, d, J 8.19 Hz, aromatic H); 7.75 (4H, J 8.19 Hz, aromatic H); 7.50-7.38 (8H, m, aromatic H), 7.29 (2H, m, aromatic H); 5.25 (2H, t, J 5.58 Hz, OH); 4.68 (4H, d, J 5.56 Hz, CH2). λmax(CH2Cl2): 216 nm (ε/Lmol−1 cm−1 177 455), 240 (57 873), 271 (56 595), 294 (55 330) 329 (37 758). FTIR (solid): 3343, 1604, 1500, 1485, 1455, 1362, 1330, 1230, 803, 745 cm−1. m/z (TOF) 544 (M+).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH3:13][CH:14]1[CH2:19][NH:18][CH2:17][CH:16]([CH3:20])[NH:15]1.C(Cl)Cl.CO>C(O)CCC>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:18]3[CH2:17][CH:16]([CH3:20])[NH:15][CH:14]([CH3:13])[CH2:19]3)=[CH:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1
Reactant: Clc1ccc2c(Cl)ccnc2c1
Reactant: CC1CNCC(C)N1
Solvent: ClCCl
Solvent: CO
Solvent: CCCCO
Product: CC1CN(c2ccnc3cc(Cl)ccc23)CC(C)N1

Procedure:
4,7-Dichloroquinoline (0.40 g, 2.0 mmol) and. 2,6-dimethylpiperazine (0.57 g, 5.0 mmol) in n-butanol (20 mL) are reacted according to method B yielding the title product after column chromatography with CH2Cl2-MeOH.
Reaction SMILES: C([S:4][CH2:5][C:6]1[C@:7]2([CH2:24][CH2:23][C@H:22]3[C:12](=[CH:13][CH:14]=[C:15]4[C@:20]3([CH3:21])[C@@H:19]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH2:18][C@H:17]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:16]4)[C@@H:9]2[CH2:10][CH:11]=1)[CH3:8])(=O)C.Br[CH2:42][CH2:43][CH2:44][C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:54][CH3:55])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH2:46][CH3:47].CO.[OH-].[K+]>O1CCCC1>[Si:26]([O:25][C@@H:19]1[C@@:20]2([CH3:21])[C:15](=[CH:14][CH:13]=[C:12]3[C@@H:22]2[CH2:23][CH2:24][C@@:7]2([CH3:8])[C@H:9]3[CH2:10][CH:11]=[C:6]2[CH2:5][S:4][CH2:42][CH2:43][CH2:44][C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:54][CH3:55])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH2:46][CH3:47])[CH2:16][C@@H:17]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:35])[CH3:36])[CH2:18]1)([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]
Reactant: CC(=O)SCC1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Reactant: CCC(CC)(CCCBr)O[Si](CC)(CC)CC
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CCC(CC)(CCCSCC1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)O[Si](CC)(CC)CC
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 91.3 %

Procedure:
To a solution of 17-acetylthiomethyl-1α,3β-bis(tert-butyldimethylsilyloxy)androsta-5,7,16-triene (274 mg, 0.454 mmol) and 1-bromo-4-ethyl-4-(triethylsilyloxy)hexane (294 mg, 0.909 mmol) in tetrahydrofuran (2 ml), was added a 1M potassium hydroxide methanol solution (3 ml) under a nitrogen atmosphere, followed by stirring at room temperature for 5 min. The thus obtained reaction mixture was partitioned by adding ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and evaporated to remove the solvent under reduced pressure. The thus obtained residue was purified by column chromatography (hexane:toluene=6:1) to give the titled compound (333 mg, 91%) as a colorless oil.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[CH3:44])[CH2:17][N:16]([C:18](=[O:37])[C@H:19]([NH:29]C(=O)OC(C)(C)C)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48]>ClCCl>[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48].[NH2:29][CH:19]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)[C:18]([N:16]1[CH2:17][C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[CH3:44])[CH2:15]1)=[O:37]
Reactant: COc1ccc(C[C@@H](NC(=O)OC(C)(C)C)C(=O)N2CC(OCCCCOCc3ccccc3)(c3ccccc3C)C2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1ccc(CC(N)C(=O)N2CC(OCCCCOCc3ccccc3)(c3ccccc3C)C2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 120.1 %

Procedure:
1.14 g (1.89 mmol) of tert-butyl [(R)-2-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]carbamate are dissolved in 10 ml of dichloromethane. 3 ml (39 mmol) of trifluoroacetic acid are added dropwise and the mixture is stirred at room temperature for 1 hour and then concentrated to dryness. 1.4 g of 2-amino-1-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-3-(4-methoxyphenyl)propan-1-one trifluoroacetate are obtained in the form of a colourless resin, in quantitative yield.
Reaction SMILES: [Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:12][CH2:13][CH:14]([C:19]1[CH:20]=[CH:21][C:22]([C:25]([OH:28])([CH3:27])[CH3:26])=[N:23][CH:24]=1)[CH2:15][CH:16]1[CH2:18][CH2:17]1>>[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:12][CH2:13][CH:14]([C:19]1[CH:24]=[N:23][C:22]([C:25]([OH:28])([CH3:26])[CH3:27])=[CH:21][CH:20]=1)[CH2:15][CH:16]1[CH2:18][CH2:17]1)=[O:6]
Reactant: CC(C)(O)c1ccc(C(CN)CC2CC2)cn1
Reactant: O=C(O)c1cccc(Cl)c1Cl
Product: CC(C)(O)c1ccc(C(CNC(=O)c2cccc(Cl)c2Cl)CC2CC2)cn1

Procedure:
From 2,3-dichlorobenzoic acid and 2-(5-(1-amino-3-cyclopropylpropan-2-yl)pyridin-2-yl)propan-2-ol. LCMS (MH+): m/z=407.1, tR (minutes, Method F)=1.98
Reaction SMILES: C(Cl)(=O)[O:2][CH2:3][CH3:4].[N:7]1[C:12]2[NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=3[C:16](=[O:18])[NH:17][C:11]=2[CH:10]=[CH:9][CH:8]=1.[CH2:23]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[CH3:24].[OH-].[Na+]>O1CCCC1>[CH2:23]([N:25]([CH2:28][CH:29]1[CH2:11][CH2:10][CH2:9][CH2:8][N:7]1[CH2:4][C:3]([N:13]1[C:14]2[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=2[C:16](=[O:18])[NH:17][C:11]2[CH:10]=[CH:9][CH:8]=[N:7][C:12]1=2)=[O:2])[CH2:26][CH3:27])[CH3:24]
Reactant: CCN(CC)CC
Reactant: CCOC(=O)Cl
Reactant: O=C1Nc2cccnc2Nc2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCN(CC)CC1CCCCN1CC(=O)N1c2ccccc2C(=O)Nc2cccnc21
Temperature: 0 °C
Reaction time: 4 h
Yield: 29.9 %

Procedure:
Ethyl chlorocarbonate (11.0 g, 0.101 mol) is added dropwise, at 0° C., to a suspension of 2-[(diethylamino)methyl]-1-piperidino acetic acid (22.83 g, 0.1 mol) in dry tetrahydrofuran (200 ml). Then, 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (21.12 g, 0.1 mol) and triethylamine (20.24 g, 0.2 mol) are added to the resulting suspension which is then stirred for a further hour at 0° C. and then for 4 hours at ambient temperature. The mixture is poured into 2N sodium hydroxide solution (1.6 liters), extracted exhaustively with dichloromethane, the organic phase concentrated to dryness and the residue purified by recrystallization from ethanol and from methanol. Colorless crystals (6.3 g) are obtained, mp. 226°-228° C., which were shown by thin layer chromatography, mixed melting point and IR spectrum to be identical to a sample prepared according to Example 34.
Reaction SMILES: [C:1]1([C:7]2[C:11]([C:12]([OH:14])=[O:13])=[CH:10][NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:15][Si](C=[N+]=[N-])(C)C>ClCCl.CO>[C:1]1([C:7]2[C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][NH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: O=C(O)c1c[nH]nc1-c1ccccc1
Solvent: ClCCl
Solvent: CO
Product: COC(=O)c1c[nH]nc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.8 %

Procedure:
To a solution of 3-phenyl-1H-pyrazole-4-carboxylic acid (1.0 g, 5.31 mmol) in dichloromethane (14.2 mL) and methanol (3.5 mL) was added trimethylsilyldiazomethane (2.66 mL, 5.31 mmol). The mixture was stirred at ambient temperature. After 30 min, additional trimethylsilyldiazomethane (0.80 mL, 1.59 mmol) was added. After 10 min, the mixture was concentrated. Purification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol) gave the title compound (0.9 g). MS 203.1 (M+1).
Reaction SMILES: [NH2:1][CH:2]1[C:22](=[O:23])[N:4]2[C:5]([C:19]([OH:21])=[O:20])=[C:6]([CH2:9][O:10][C:11](=[O:18])[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:7][S:8][C@H:3]12.C[Si](CC(N)=O)(C)C.P(Cl)(Cl)(Cl)=O.[CH:37]([NH:39][C:40]1[S:41][C:42]([Br:52])=[C:43]([C:45](=[N:49][O:50][CH3:51])[C:46](O)=[O:47])[N:44]=1)=[O:38]>C(OCC)(=O)C.CN(C)C=O>[CH:37]([NH:39][C:40]1[S:41][C:42]([Br:52])=[C:43]([C:45](=[N:49][O:50][CH3:51])[C:46]([NH:1][CH:2]2[C:22](=[O:23])[N:4]3[C:5]([C:19]([OH:21])=[O:20])=[C:6]([CH2:9][O:10][C:11](=[O:18])[C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:7][S:8][C@H:3]23)=[O:47])[N:44]=1)=[O:38]
Reactant: CON=C(C(=O)O)c1nc(NC=O)sc1Br
Reactant: NC1C(=O)N2C(C(=O)O)=C(COC(=O)c3ccccc3)CS[C@H]12
Agent: C[Si](C)(C)CC(N)=O
Solvent: O=P(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(COC(=O)c3ccccc3)CS[C@H]12)c1nc(NC=O)sc1Br
Yield: 34.4 %

Procedure:
A solution of 7-amino-3-benzoyloxymethyl-3-cephem-4-carboxylic acid (0.67 g.) and trimethylsilylacetamide (2.1 g.) in dry ethyl acetate (20 ml.) and a solution of dimethylformamide (0.2 ml.), phosphoryl chloride (0.24 ml.) and 2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer, 0.62 g.) in dry ethyl acetate (1 ml.) were treated in a similar manner to that of Example 1-(1) to give 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-benzoyloxymethyl-3-cephem-4-carboxylic acid (syn isomer, 430 mg.).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]#[C:7][CH2:8][CH2:9][CH:10]=O.[Cl-].[CH2:13]([N:17]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:18](=[O:20])[CH3:19])[CH:14]([CH3:16])[CH3:15]>>[CH2:13]([NH:17][C:18](=[O:20])/[CH:19]=[CH:10]/[CH2:9][CH2:8][C:7]#[C:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH:14]([CH3:16])[CH3:15]
Reactant: O=CCCC#Cc1cccs1
Reactant: CC(=O)N(CC(C)C)[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Product: CC(C)CNC(=O)/C=C/CCC#Cc1cccs1

Procedure:
N-isobutyl 7-thienyl-(2E)-hepten-6-ynamide was prepared from 5-thienyl-4-pentyn-1-al and N-isobutyl acetamidotriphenyl-phosphonium chloride as in Example 9 and then converted to the title product by semihydrogenation as in Example 9.
Reaction SMILES: O=[C:2]([CH2:8][C:9](=O)[C:10]1[CH:14]=[CH:13][S:12][CH:11]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].C1C=CC=CC=1.[CH3:22][CH:23]([N:25]1[C:29]([NH2:30])=[CH:28][CH:27]=[N:26]1)[CH3:24]>C(O)(=O)C>[CH3:22][CH:23]([N:25]1[C:29]2[N:30]=[C:9]([C:10]3[CH:14]=[CH:13][S:12][CH:11]=3)[CH:8]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:28]=2[CH:27]=[N:26]1)[CH3:24]
Reactant: CCOC(=O)C(=O)CC(=O)c1ccsc1
Reactant: CC(C)n1nccc1N
Solvent: c1ccccc1
Solvent: CC(=O)O
Product: CCOC(=O)c1cc(-c2ccsc2)nc2c1cnn2C(C)C

Procedure:
The title compound was prepared in the same manner as described for intermediate 61 using ethyl 2,4-dioxo-4-(3-thienyl)butanoate (542 mg, 2.397 mmol), benzene (5 mL), 1-(1-methylethyl)-1H-pyrazol-5-amine (300 mg, 2.397 mmol), and acetic acid (5 ml). The crude product was purified using column chromatography (silica gel, eluent: 0 to 100% EtOAc/hexanes) to afford the product as 590 mg (78%). LCMS E-S (M+H)=315.8. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.53 (t, J=6.8 Hz, 3H), 1.66 (d, J=6.8 Hz, 6H), 4.56 (q, J=7.1 Hz, 2H), 5.43 (spt, J=6.7 Hz, 1H), 7.47 (dd, J=5.1, 3.0 Hz, 1H), 7.84-7.95 (m, 1H), 8.08-8.18 (m, 2H), 8.32-8.43 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[O:28][CH3:29])[NH:21][N:20]=2)[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])(=[O:9])=[O:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:37][C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=1)[C:41]([O:43][CH3:44])=[O:42]>CN(C=O)C.C(Cl)Cl.O>[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:16])[CH3:17])[C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[O:28][CH3:29])[N:21]([CH2:37][C:38]3[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=3)[C:41]([O:43][CH3:44])=[O:42])[N:20]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1
Reactant: COC(=O)c1cccc(CBr)c1
Reactant: COc1cccc2[nH]nc(N(COCC[Si](C)(C)C)S(=O)(=O)c3ccc(Cl)s3)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCl
Product: COC(=O)c1cccc(Cn2nc(N(COCC[Si](C)(C)C)S(=O)(=O)c3ccc(Cl)s3)c3c(OC)cccc32)c1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
A solution of 5-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide (for a preparation see Intermediate 8) (1 g, 2.11 mmol) in DMF (10 mL) was treated at ambient temperature with potassium carbonate (0.583 g, 4.22 mmol) and methyl 3-(bromomethyl)benzoate (Alfa Aesar) (0.580 g, 2.53 mmol). The resulting mixture was stirred at 50° C. for 2 h and the LCMS then showed product as the major peak. The mixture was diluted with DCM (20 mL) and of water (20 mL). The organic phase was separated and the aqueous layer was further extracted with DCM (20 mL). The combined organic solutions were washed with brine (30 mL), dried over an hydrophobic frit, and concentrated under reduced pressure.
Reaction SMILES: [NH2:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([N+:12]([O-:14])=[O:13])=[CH:7][CH:8]=2)[CH2:3]1.[C:15](Cl)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1.C([O-])([O-])=O.[K+].[K+].O>[C:16]1([C:15]([NH:1][CH:2]2[CH2:11][CH2:10][C:9]3[C:4](=[CH:5][C:6]([N+:12]([O-:14])=[O:13])=[CH:7][CH:8]=3)[CH2:3]2)=[O:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: NC1CCc2ccc([N+](=O)[O-])cc2C1
Reactant: O=C(Cl)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(NC1CCc2ccc([N+](=O)[O-])cc2C1)c1ccccc1

Procedure:
To 2-amino-7-nitrotetralin (1.8 g, 9.39 mmol, derived from dibenzoyl-D-tartaric acid) in THF (50 ml) and 10% K2CO3 (100 ml) was added benzoyl chloride (1.2 ml, 10.1 mmol). After the addition was complete, the mixture was diluted with water to a volume of 250 ml. The precipatated solids were collected by filtration, washed with water and dried in vacuo: (2.8 g, 100%), m.p. 208°-209° C., [α]D +21.9° (c 0.33 DMSO).
Reaction SMILES: C[O:2][C:3](=[O:47])[C@H:4]([CH2:24][CH2:25][CH2:26][CH2:27][NH:28][C:29](=[O:46])/[CH:30]=[CH:31]/[CH:32]=[CH:33]/[C:34]1[CH:39]=[C:38]([O:40][CH3:41])[C:37]([O:42][CH3:43])=[C:36]([O:44][CH3:45])[CH:35]=1)[NH:5][C:6](=[O:23])/[CH:7]=[CH:8]/[CH:9]=[CH:10]/[C:11]1[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=1.[OH-].[K+].Cl>CO.O1CCCC1>[CH3:22][O:21][C:13]1[CH:12]=[C:11](/[CH:10]=[CH:9]/[CH:8]=[CH:7]/[C:6]([NH:5][C@H:4]([C:3]([OH:47])=[O:2])[CH2:24][CH2:25][CH2:26][CH2:27][NH:28][C:29](=[O:46])/[CH:30]=[CH:31]/[CH:32]=[CH:33]/[C:34]2[CH:35]=[C:36]([O:44][CH3:45])[C:37]([O:42][CH3:43])=[C:38]([O:40][CH3:41])[CH:39]=2)=[O:23])[CH:16]=[C:15]([O:17][CH3:18])[C:14]=1[O:19][CH3:20]
Reactant: COC(=O)[C@H](CCCCNC(=O)/C=C/C=C/c1cc(OC)c(OC)c(OC)c1)NC(=O)/C=C/C=C/c1cc(OC)c(OC)c(OC)c1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: COc1cc(/C=C/C=C/C(=O)NCCCC[C@H](NC(=O)/C=C/C=C/c2cc(OC)c(OC)c(OC)c2)C(=O)O)cc(OC)c1OC
Temperature: 25 °C
Reaction time: 3 h
Yield: 79.5 %

Procedure:
Added to a solution of 265 mg (0.40 mmol) of Nα,Nε-bis[5-(3,4,5-trimethoxyphenyl)penta-(2E,4E)-dienoyl]-lysine methyl ester synthesized by the process of Example 9 in methanol-tetrahydrofuran (1 ml-1 ml) was 1.0 ml (5.0 mmol) of a 5N aqueous solution of potassium hydroxide, and the mixture was stirred for 3 hours at room temperature. A saturated saline solution (3 ml) and concentrated hydrochloric acid (0.5 ml) were added to the reaction mixture to conduct extraction with chloroform. An organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The resultant crude oil (234 mg) was purified by column chromatography on silica gel to obtain 203 mg (yield: 80%) of the title compound as a colorless amorphous powder.
Reaction SMILES: [CH2:1]([O:4][CH:5]1[O:10][C:9]([CH2:13][OH:14])([CH2:11][OH:12])[C@@H:8]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:7]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:6]1[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH:2]=[CH2:3].[H-].[Na+].Br[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=1>CN(C)C=O>[CH2:1]([O:4][CH:5]1[O:10][C:9]([CH2:11][O:12][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)([CH2:13][O:14][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[C@@H:8]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:7]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@H:6]1[O:31][CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH:2]=[CH2:3]
Reactant: COc1ccc(CBr)cc1
Reactant: C=CCOC1OC(CO)(CO)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCOC1OC(COCc2ccc(OC)cc2)(COCc2ccc(OC)cc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 0 °C
Yield: 51.7 %

Procedure:
The starting diol [((3S,4S,5R)-6-allyloxy-3,4,5-tris-benzyloxy-2-hydroxymethyl-tetrahydro-pyran-2-yl)-methanol (I-1b: 10 g, 19.208 mmol) was dissolved in N,N-dimethylformamide (70 mL) and cooled to 0° C. Sodium hydride (60% dispersion in mineral oil, 1.69 g, 42.3 mmol) was added and the reaction was allowed to stir at 0° C. for 1 hour before the addition of 1-bromomethyl-4-methoxy-benzene (5.96 mL, 40.3 mmol). The reaction was then heated to 60° C. overnight. The mixture was cooled down to room temperature and the reaction was quenched with water and extracted with ethyl acetate (2 times). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The reaction was then chromatographed over silica gel (eluting with a gradient of 0 to 80% ethyl acetate in heptane) yielding 7.55 g (52% yield) of product (I-1c). MS 778.8 (M+NH4+; positive mode).
Reaction SMILES: [CH3:1][CH2:2][C:3](=O)[CH2:4][CH3:5].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:21][C@@H:22]1[C@H:27]([NH:28][C:29]([C:31]2[NH:32][C:33]([CH2:37][CH3:38])=[C:34]([Cl:36])[N:35]=2)=[O:30])[CH2:26][CH2:25][N:24]([C:39]2[S:40][C:41]3[C:47]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:46][CH:45]=[CH:44][C:42]=3[N:43]=2)[CH2:23]1.C(=O)(O)[O-].[Na+]>CO.O1CCCC1>[Cl:36][C:34]1[N:35]=[C:31]([C:29]([NH:28][C@@H:27]2[CH2:26][CH2:25][N:24]([C:39]3[S:40][C:41]4[C:47]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:46][CH:45]=[CH:44][C:42]=4[N:43]=3)[CH2:23][C@@H:22]2[NH:21][CH:3]([CH2:4][CH3:5])[CH2:2][CH3:1])=[O:30])[NH:32][C:33]=1[CH2:37][CH3:38]
Reactant: CCC(=O)CC
Reactant: CCOC(=O)c1cccc2nc(N3CC[C@@H](NC(=O)c4nc(Cl)c(CC)[nH]4)[C@@H](N)C3)sc12
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CCOC(=O)c1cccc2nc(N3CC[C@@H](NC(=O)c4nc(Cl)c(CC)[nH]4)[C@@H](NC(CC)CC)C3)sc12
Temperature: 25 °C
Reaction time: 15 h
Yield: 67.5 %

Procedure:
3-Pentanone (68.9 μL, 0.65 mmol) and sodium triacetoxyborohydride (165 mg, 0.78 mmol) were added four times every two hours to a mixed solution of ethyl 2-[(3S,4R)-3-amino-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}piperidin-1-yl]-1,3-benzothiazole-7-carboxylate obtained in Example (202e) (62.0 mg, 0.13 mmol) in methanol (1 mL) and tetrahydrofuran (1 mL) under ice-cooling, and the mixture was stirred at room temperature for 15 hours. Saturated aqueous sodium bicarbonate solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluate: hexane:ethyl acetate=1:1 v/v) to obtain 48 mg of the title compound (68%) as a colorless solid.