Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C@H:5]([CH2:15][O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@H:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:14])[OH:7])(=O)C.C([O-])([O-])=O.[K+].[K+]>CO.O>[CH2:17]([O:16][CH2:15][C@@H:5]([OH:4])[C@H:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:14])[OH:7])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC(=O)O[C@H](COCc1ccccc1)[C@@H](O)c1ccccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: O[C@H](COCc1ccccc1)[C@@H](O)c1ccccc1Cl
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 95.4 %

Procedure:
To a solution of (1S,2R)-3-(benzyloxy)-1-(2-chlorophenyl)-1-hydroxypropan-2-yl acetate (Preparation example 374, 1.2 g, 3.58 mmole) in MeOH (16.2 mL) and H2O (1.8 mL) was added K2CO3 (1.48 g, 10.74 mmole) at 0° C. The mixture was stirred for 1.5 hr at 0° C. The TLC showed complete consumption of SM. The reaction mixture was quenched with H2O at 0° C. then extracted with EtOAc. The aqueous layer was extracted with EtOAc and separated. The combined organic layer was washed with H2O, then dried over MgSO4 and evaporated under reduced pressure. The crude compound was purified by silica ge column to produce the title compound (1.0 g, 94%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](O)=[O:8])=[CH:5][C:4]=1/[CH:12]=[CH:13]/[C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1.[NH2:25][CH2:26][CH2:27][C:28]#[N:29]>>[C:26]([CH2:27][CH2:28][NH:29][C:7](=[O:8])[C:6]1[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[C:4](/[CH:12]=[CH:13]/[C:14]2[CH:15]=[CH:16][C:17]([O:20][C:21]([F:23])([F:22])[F:24])=[CH:18][CH:19]=2)[CH:5]=1)#[N:25]
Reactant: N#CCCN
Reactant: COc1ccc(C(=O)O)cc1/C=C/c1ccc(OC(F)(F)F)cc1
Product: COc1ccc(C(=O)NCCC#N)cc1/C=C/c1ccc(OC(F)(F)F)cc1

Procedure:
The captioned compound was synthesized from 4-methoxy-3-[(E)-2-(4-trifluoromethoxyphenyl)vinyl]benzoic acid obtained in step B of Example 2-2-1 and 3-aminopropionitrile in accordance with the same procedure as in the methods described in step C of Example 1-2-3.
Reaction SMILES: [BH4-].[Na+].C(N)CN.[CH3:7][O:8][C:9](=[O:35])[CH2:10][CH2:11][CH2:12][C:13]#[C:14][CH2:15][N:16]1[C@@H:20]([CH2:21][O:22][C:23](=[O:33])[NH:24][CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:19][CH2:18][C:17]1=[O:34]>C(O)C.[Ni](Cl)Cl>[CH3:7][O:8][C:9](=[O:35])[CH2:10][CH2:11][CH2:12]/[CH:13]=[CH:14]\[CH2:15][N:16]1[C@@H:20]([CH2:21][O:22][C:23](=[O:33])[NH:24][CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:19][CH2:18][C:17]1=[O:34]
Reactant: COC(=O)CCCC#CCN1C(=O)CC[C@@H]1COC(=O)NCCc1ccccc1
Agent: Cl[Ni]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: NCCN
Product: COC(=O)CCC/C=C\CN1C(=O)CC[C@@H]1COC(=O)NCCc1ccccc1
Reaction time: 0.25 h
Yield: 57.3 %

Procedure:
95% Ethanol (1.0 mL) was added to a slowly stirred mixture of nickel (II) chloride (86 mg, 0.66 mmol) and sodium borohydride (12 mg, 0.33 mmol) under nitrogen. The mixture immediately turned black. After 15 min, ethylenediamine (70 μL, 1.04 mmol) was added. After an additional 15 min, a solution of alkyne 13 (53 mg, 0.13 mmol) in 95% ethanol (1.0 mL) was added. The flask was evacuated and refilled with hydrogen (3×), and the reaction mixture was stirred vigorously under a balloon of hydrogen for 22 h. The mixture was then filtered through celite, washing with MEOH (5 mL) and the filtrate was concentrated in vacuo. Purification of the residue by flash column chromatography on silica (100% CH2Cl2→50% EtOAc/CH2Cl2, gradient) afforded 30 mg (56%) of the title compound (15).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]([O:26]C3CCCCO3)[CH2:11][O:12][CH2:13][CH2:14]OS(C3C=CC(C)=CC=3)(=O)=O)[CH:8]=[CH:9][C:2]1=2.[CH3:33][NH2:34].C(OCC)C.[ClH:40].C(O)C>C(O)C.CC(C)=O>[ClH:40].[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]([OH:26])[CH2:11][O:12][CH2:13][CH2:14][NH:34][CH3:33])[CH:8]=[CH:9][C:2]1=2
Reactant: Cc1ccc(S(=O)(=O)OCCOCC(OC2CCCCO2)c2ccc3sccc3c2)cc1
Reactant: CN
Agent: Cl
Solvent: CC(C)=O
Solvent: CCOCC
Solvent: CCO
Product: CNCCOCC(O)c1ccc2sccc2c1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
In 15 ml of ethanol was dissolved 1.5 g of 1-(benzo[b]thiophen-5-yl)-1-(2-tetrahydropyranyloxy)-2-[2-(p-toluenesulfonyloxy)ethoxy]ethane. To the solution was added 4.9 ml of a 40% aqueous methylamine solution. The resulting mixture was refluxed for 1 hour. The reaction mixture was added to a mixture of 20 ml of ice water and 20 ml of diethyl ether. The organic layer was separated. The aqueous layer was extracted with 20 ml of diethyl ether. The extract was combined with the previously separated organic layer. To the combined organic layer was added 20 ml of water. The resulting mixture was adjusted to pH 1.5 with 6N hydrochloric acid and stirred at room temperature for 20 minutes. The aqueous layer was separated. The organic layer was extracted with 10 ml of water. The extract was combined with the previously separated aqueous layer. To the combined aqueous layer was added 30 ml of methylene chloride. The resulting mixture was adjusted to pH 11 with a 10% aqueous sodium hydroxide solution. The organic layer was separated. The aqueous layer was extracted with 15 ml of methylene chloride. The extract was combined with the previously separated organic layer and the combined organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue thus obtained was dissolved in 7 ml of acetone. To the solution was added 0.5 ml of a 5N dry hydrogen chloride-ethanol solution. The resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 7 ml of diethyl ether. The resulting crystals were collected by filtration to obtain 0.5 g of 1-(benzo[b]thiophen-5-yl)-2-(N-methylaminoethoxy)ethanol hydrochloride (compound No. 347).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@:12](C(C)(C)C)([CH2:13][NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)[CH2:11][O:10][C:9]1([CH3:27])[CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO[CH:30](OC)[C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1>>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)[CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[CH2:11][O:10][C:9]1([CH3:27])[CH3:26])=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: COc1ccc(C(OC)OC)cc1
Reactant: CC(C)(C)OC(=O)N1C(C)(C)OC[C@@]1(CNc1cccc(Cl)c1)C(C)(C)C
Product: COc1ccc(CN(C[C@H]2COC(C)(C)N2C(=O)OC(C)(C)C)c2cccc(Cl)c2)cc1

Procedure:
In analogy to example 20.a tert-butyl (S)-4-[(3-chloro-phenylamino)-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester was reacted with p-anisaldehyde dimethyl acetal to give (S)-4-{[(3-chloro-phenyl)-(4-methoxy-benzyl)-amino]-methyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester. White solid. MS (ISP): 463.1 ([{37Cl}M+H]+), 461.1 ([{35Cl}M+H]+)
Reaction SMILES: Br[CH2:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][N:4]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][CH3:20])=[CH:15][CH:14]=1>>[F:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]([CH3:20])[CH2:2][C:3]2[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][N:4]=2)=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1cccnc1CBr
Reactant: CNc1ccc(F)cc1
Product: CN(Cc1ncccc1[N+](=O)[O-])c1ccc(F)cc1
Yield: 80 %

Procedure:
In accordance with the same procedures as in Step 1 of Preparation 2, except for using 2-bromomethyl-3-nitropyridine prepared in Step 2 of Preparation 1 and (4-fluorophenyl)-methylamine, the titled compound was obtained as yellow solid. (Yield: 80%)
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:20]=2[N:19]=[CH:18][CH:17]=[CH:16]3)[CH:10]=1)=O)C.[H-].C([Al+]CC(C)C)C(C)C>>[N:19]1[C:20]2[C:15](=[CH:14][CH:13]=[CH:12][C:11]=2[N:9]2[CH:10]=[C:6]([CH2:4][OH:3])[N:7]=[CH:8]2)[CH:16]=[CH:17][CH:18]=1
Reactant: CCOC(=O)c1cn(-c2cccc3cccnc23)cn1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Product: OCc1cn(-c2cccc3cccnc23)cn1

Procedure:
Following the general method described in example 388, 1-quinolin-8-yl-1H-imidazole-4-carboxylic acid ethyl ester was reacted with diisobutylaluminum hydride. After hydrolytic workup and chromatography the title compound was obtained as a light brown crystalline solid. Mp. 168-170° C. (Et2O), MS: m/e=225 (M+).
Reaction SMILES: [CH:1]([NH:3][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12])=O.[H-].[Na+].ClC1[N:22]=[C:21]([O:23][CH3:24])[N:20]=[C:19]([O:25][CH3:26])[N:18]=1.[OH-].[Na+]>O1CCCC1>[CH3:26][O:25][C:19]1[N:20]=[C:21]([O:23][CH3:24])[N:22]=[C:1]([NH:3][C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=2[N+:11]([O-:13])=[O:12])[N:18]=1
Reactant: COc1nc(Cl)nc(OC)n1
Reactant: Cc1ccc(NC=O)c([N+](=O)[O-])c1
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1nc(Nc2ccc(C)cc2[N+](=O)[O-])nc(OC)n1
Reaction time: 0.17 h
Yield: 86.1 %

Procedure:
N-formyl-4-methyl-2-nitroaniline (7.2 g) was dissolved in tetrahydrofuran (50 ml), and sodium hydride (60% purity, oily) (2.0 g) was added thereto at room temperature. After stirring for 10 minutes, 2-chloro-4,6-dimethoxy-[1,3,5]triazine (7.0 g) was added at room temperature, followed by stirring for 3 hours. A 10% aqueous sodium hydroxide solution was added thereto, and the crystals were collected by filtration, washed with water and dried to obtain 10.0 g of the desired product as a yellow powder (m.p. 189-191° C.).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[S:9]([N:12]([CH2:22][C:23](OCC)=[O:24])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C>ClCCl>[CH3:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([CH2:28][N:8]([S:9]([N:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)[CH2:22][CH:23]=[O:24])(=[O:11])=[O:10])[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:34][CH:33]=1
Reactant: CCOC(=O)CN(Cc1ccc(OC)cc1)S(=O)(=O)N(Cc1ccc(OC)cc1)C(=O)OC(C)(C)C
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: ClCCl
Product: COc1ccc(CN(CC=O)S(=O)(=O)N(Cc2ccc(OC)cc2)C(=O)OC(C)(C)C)cc1
Temperature: -78 °C
Reaction time: 3 h
Yield: 72.1 %

Procedure:
A solution of ethyl [{[(tert-butoxycarbonyl)(4-methoxybenzyl)amino]sulfonyl}(4-methoxybenzyl)amino]acetate (5.30 g, 10 mmol) in dichloromethane (20.0 mL) at −78° C. under N2 was treated with 1.0 M diisobutylaluminum hydride in dichloromethane (12.2 mL, 12.2 mmol, 1.22 equiv.). The reaction mixture was stirred at −78° C. for 3 h. The reaction was then quenched with methanol (3 mL) and treated with dichloromethane (100 mL) and a saturated solution of sodium potassium tartrate (150 mL). This solution was stirred at room temperature overnight. The aqueous layer was then extracted with dichloromethane (3×20 mL). The combined dichloromethane solution was washed with brine, dried over sodium sulfate and concentrated. The residue was then purified on silica gel (0-30% ethyl acetate/hexane gradient elution) to give the desired product (3.45 g, 71%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.23 (m, 4H), 6.88 (m, 4H), 4.68 (s, 2H), 4.31 (s, 2H), 4.07 (s, 2H), 3.72 (s, 3H), 3.71 (s, 3H), 1.40 (s, 9H).
Reaction SMILES: [NH:1]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:2]([C:13]([NH:15][C@H:16]([C:21]([OH:23])=O)[CH2:17][CH:18]([CH3:20])[CH3:19])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[NH:31]([CH3:40])[C@H:32]([C:37]([NH2:39])=[O:38])[CH2:33][CH2:34][CH2:35][CH3:36].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1>>[NH:1]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:2]([C:13]([NH:15][C@H:16]([C:21]([N:31]([CH3:40])[C@H:32]([C:37]([NH2:39])=[O:38])[CH2:33][CH2:34][CH2:35][CH3:36])=[O:23])[CH2:17][CH:18]([CH3:19])[CH3:20])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1
Reactant: CCCC[C@H](NC)C(N)=O
Reactant: CC(C)C[C@H](NC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)OC(C)(C)C)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Product: CCCC[C@@H](C(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)OC(C)(C)C
Yield: 99 %

Procedure:
Condensation of BocDTrp-LeuOH (Example 38, 2.09 g.) and MeNleNH2 (1.00 g.) using dicyclohexylcarbodiimide and 1-hydroxybenzotriazole gave BocDTrp-Leu-MeNleNH2 in 99% yield. De-t-butoxycarbonylation of BocDTrp-Leu-MeNleNH2 (2.50 g.) using trifluoroacetic acid in dimethyl sulfide and ethanedithiol gave HDTrp-Leu-MeNleNH2 in 37% yield.
Reaction SMILES: [CH:1]1([NH:7][C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([OH:16])=O)[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:20][C:19]=1[O:29][CH3:30]>C(Cl)Cl>[CH:1]1([NH:7][C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:20][C:19]=3[O:29][CH3:30])=[O:16])[CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C(O)c1cc(NC2CCCCC2)ncn1
Reactant: COc1cc(NS(C)(=O)=O)ccc1N
Solvent: ClCCl
Product: COc1cc(NS(C)(=O)=O)ccc1NC(=O)c1cc(NC2CCCCC2)ncn1

Procedure:
Following the general method as outlined in Example 1, starting from 6-(cyclohexylamino)pyrimidine-4-carboxylic acid (Intermediate 4) and N-(4-amino-3-methoxyphenyl)methanesulfonamide (Kaironkem), the title compound was obtained as a white solid after trituration in DCM.
Reaction SMILES: [BH4-].[Li+].Cl[Si](C)(C)C.[NH2:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])[C:10](O)=[O:11].[OH-].[Na+]>C1COCC1>[NH2:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])[CH2:10][OH:11]
Reactant: N[C@@H](Cc1ccc(Cl)cc1Cl)C(=O)O
Agent: C[Si](C)(C)Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: N[C@H](CO)Cc1ccc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A solution of lithium tetrahydroborate (190 mg, 8.50 mmol) in THF (4 mL) was cooled to 0° C. Chlorotrimethylsilane (2.2 mL, 17 mmol) was added dropwise. The mixture was stirred for 20 minutes at room temperature and then returned to 0° C. (S)-2-amino-3-(2,4-dichlorophenyl)propanoic acid (1.00 g, 4.27 mmol) was then added. The reaction was allowed to warm up slowly to room temperature while stirring overnight. The mixture was cooled to 0° C. and quenched by slow addition of methanol (1 mL) followed by an aqueous solution of 2N sodium hydroxide (4.2 mL, 8.54 mmol). Volatiles were removed under reduces pressure. The slurry was diluted with water (5 mL) and extracted with DCM (3×15 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to afford (S)-2-amino-3-(2,4-dichlorophenyl)propan-1-ol as a solid that was used in the next step without further purification. MS m/z 220 (M+).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CS(O)(=O)=O.[CH:12]([Si:15]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])Cl)([CH3:14])[CH3:13].[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[CH:12]([Si:15]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[N:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1)([CH3:14])[CH3:13]
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Reactant: C1CNCCN1
Agent: CS(=O)(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Product: CC(C)[Si](C(C)C)(C(C)C)N1CCNCC1
Temperature: 130 °C
Reaction time: 10 h

Procedure:
A flask equipped with a stirrer, reflux condenser, dropping funnel and thermometer was charged with 189.4 g (2.2 mol) of piperazine, 200 ml of xylene, and 1.0 g (0.01 mol) of methanesulfonic acid and heated at 130° C. Once the internal temperature became steady, 192.8 g (1.0 mol) of triisopropylchlorosilane was added dropwise over 2 hours. Stirring was continued for 10 hours at the temperature. The reaction solution was cooled to room temperature, to which 500 g of a 10 wt % sodium hydroxide aqueous solution was added. The organic layer was separated. On distillation, 132.6 g of a fraction having a boiling point of 109-111° C./0.4 kPa was collected, which was 1-triisopropylsilylpiperazine.
Reaction SMILES: [CH:1]1([NH:4][CH2:5][CH2:6][CH2:7][C:8]2([CH3:27])[S:12][C:11]([NH:13][C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])[CH3:15])=[N:10][C:9]2=[O:26])[CH2:3][CH2:2]1.[O:28]1[CH:32]=[CH:31][C:30]([C:33](O)=[O:34])=[CH:29]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH:1]1([N:4]([CH2:5][CH2:6][CH2:7][C:8]2([CH3:27])[S:12][C:11]([NH:13][C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:23])([F:25])[F:24])[CH3:15])=[N:10][C:9]2=[O:26])[C:33]([C:30]2[CH:31]=[CH:32][O:28][CH:29]=2)=[O:34])[CH2:2][CH2:3]1
Reactant: C[C@H](NC1=NC(=O)C(C)(CCCNC2CC2)S1)c1ccccc1C(F)(F)F
Reactant: O=C(O)c1ccoc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C[C@H](NC1=NC(=O)C(C)(CCCN(C(=O)c2ccoc2)C2CC2)S1)c1ccccc1C(F)(F)F
Reaction time: 8 h

Procedure:
The mixture of 5-(3-(cyclopropylamino)propyl)-5-methyl-2-((S)-1-(2-(trifluoromethyl)-phenyl)ethylamino)thiazol-4(5H)-one (0.106 g, 0.265 mmol), 3-furoic acid (0.0297 g, 0.265 mmol), TBTU (0.0895 g, 0.279 mmol), and N,N-diisopropylethylamine (0.0555 ml, 0.318 mmol) in DMF (3.0 mL) was stirred at ambient temp. overnight. The mixture was partitioned between EtOAc and Na2CO3 (aq), and the combined organic portions were washed with brine. The solvents were removed in vacuo, and the residue was purified by flash column chromatography (0 to 100% of EtOAc in hexanes) to give the title compound as a white solid. MS m/z: 494.1 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)=[CH:13][C:12]([C:22](OC)=[O:23])=[CH:11][C:10]=1[C:26]([CH3:29])([CH3:28])[CH3:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C(OCC)C.ClCCl.[O-2].[O-2].[Mn+4]>[CH2:1]([O:8][C:9]1[C:14]([C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)=[CH:13][C:12]([CH:22]=[O:23])=[CH:11][C:10]=1[C:26]([CH3:29])([CH3:28])[CH3:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)c1cc(-c2ccc(C)cc2)c(OCc2ccccc2)c(C(C)(C)C)c1
Agent: [Mn+4]
Agent: [Al+3]
Agent: [H-]
Solvent: ClCCl
Solvent: O
Solvent: CCOCC
Product: Cc1ccc(-c2cc(C=O)cc(C(C)(C)C)c2OCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 85 %

Procedure:
1 g (2.6 mmol) of methyl 6-benzyloxy-5-tert-butyl-4′-methyl-3-biphenylcarboxylate is dissolved in 40 mL of anhydrous ethyl ether, and the medium is cooled to 0° C. 130 mg (3.3 mmol) of lithium aluminum hydride are added and the reaction medium is stirred for 1 hour. The reaction is hydrolysed by sequential addition of 130 μL of water, 130 μL of 15% sodium hydroxide solution and 400 μL of water. The reaction medium is filtered and the filtrate is concentrated under reduced pressure. The residue obtained is dissolved in 30 mL of dichloromethane, and 2 g (23 mmol) of manganese dioxide are added. The medium is refluxed for 5 hours, and filtered through Celite. A yellow oil is obtained (m=780 mg; yield=85%).
Reaction SMILES: [N:1]([C:10]([CH3:16])([CH3:15])[C:11]([O:13]C)=O)=[N:2][C:3]([CH3:9])([CH3:8])[C:4]([O:6]C)=O.[NH2:17][CH2:18][CH2:19][NH:20][CH2:21][CH2:22][OH:23].[Cl-].[Na+]>CO>[N:2]([C:3]([CH3:8])([CH3:9])[C:4]([NH:17][CH2:18][CH2:19][NH:20][CH2:21][CH2:22][OH:23])=[O:6])=[N:1][C:10]([CH3:16])([CH3:15])[C:11]([NH:17][CH2:18][CH2:19][NH:20][CH2:21][CH2:22][OH:23])=[O:13]
Reactant: NCCNCCO
Reactant: COC(=O)C(C)(C)N=NC(C)(C)C(=O)OC
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(N=NC(C)(C)C(=O)NCCNCCO)C(=O)NCCNCCO
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.7 %

Procedure:
To a constantly stirred mixture comprising 23.0 g of V-601, 22.9 g of 2-(2-aminoethylamino)ethanol and 5 ml of methanol, 4.7 g of 28% CH3 ONa was added dropwise. The reaction was carried out with stirring at room temperature for 8 hours. After standing overnight, the reaction mixture was mixed with 50 ml of saturated sodium chloride solution, and extracted with 100 ml of dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and solvent was distilled off, and there was obtained 29.8 g (yield 80%) of 2,2'-azobis[N-(2-hydroxyethylamino)ethyl-2-methylpropionamide] of yellow viscous liquid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][CH:12]=[CH:11][C:10]=2[O:17][CH3:18])=[O:5])[CH3:2].[CH3:19][S:20]([CH2:23][CH2:24][NH2:25])(=[O:22])=[O:21]>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:25][CH2:24][CH2:23][S:20]([CH3:19])(=[O:22])=[O:21])=[CH:13][CH:12]=[CH:11][C:10]=2[O:17][CH3:18])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cnc2c(OC)cccc2c1Cl
Reactant: CS(=O)(=O)CCN
Product: CCOC(=O)c1cnc2c(OC)cccc2c1NCCS(C)(=O)=O

Procedure:
4-Chloro-8-methoxy-quinoline-3-carboxylic acid ethyl ester (266 mg, 1.0 mmol) was treated with 2-methanesulfonyl-ethylamine following general procedure B to afford 4-(2-methanesulfonyl-ethylamino)-8-methoxy-quinoline-3-carboxylic acid ethyl ester (305 mg). Thus obtained amino-ester (70 mg, 0.2 mmol) was subjected to reaction with 5-Isocyanato-benzo[1,3]dioxole according to general procedure C to furnish 3-Benzo[1,3]dioxol-5-yl-1-(2-methanesulfonyl-ethyl)-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione (43 mg). LCMS: m/z 471 [M+1]+.
Reaction SMILES: C(OC([N:11]1[CH2:15][CH2:14][C:13]([CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]3=[O:35])=[CH:21][C:20]=2[F:36])([OH:16])[CH2:12]1)=O)C1C=CC=CC=1>[Pd].C(OCC)(=O)C.CO>[F:36][C:20]1[CH:21]=[C:22]([N:25]2[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]2=[O:35])[CH:23]=[CH:24][C:19]=1[O:18][CH2:17][C:13]1([OH:16])[CH2:14][CH2:15][NH:11][CH2:12]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(OCC3(O)CCN(C(=O)OCc4ccccc4)C3)c(F)c2)C(=O)O1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(=O)NC[C@H]1CN(c2ccc(OCC3(O)CCNC3)c(F)c2)C(=O)O1

Procedure:
A suspension of 660 mg 3-{4-[(5S)-5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2-fluoro-phenoxymethyl}-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester (MW: 501.51, 1.31 mmol) and 20 mg palladium 10% on activated carbon in 20 ml of a 1/1 ethyl acetate/methanol mixture was stirred for twelve hours under hydrogen. The catalyst was filtered on a glass fiber filter paper and the filtrate evaporated under reduced pressure to afford a colorless oil. Yield: 400 mg, 83.2%. MS: 368.4 (M+H)+, Method ESI+.
Reaction SMILES: C(SCC)C.[Al+3].[Cl-].[Cl-].[Cl-].C[O:11][C:12]1[C:13]([CH3:33])=[CH:14][C:15]2[CH2:21][CH:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[CH2:17][C:16]=2[CH:32]=1>C(Cl)Cl>[OH:11][C:12]1[C:13]([CH3:33])=[CH:14][C:15]2[CH2:21][CH:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[CH2:17][C:16]=2[CH:32]=1
Reactant: CCOC(=O)CC1Cc2cc(C)c(OC)cc2Cc2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCSCC
Solvent: ClCCl
Product: CCOC(=O)CC1Cc2cc(C)c(O)cc2Cc2ccccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 53.7 %

Procedure:
To dry CH2Cl2 (30 mL) cooled in an ice bath was added diethylsulfide (0.38 mL, 3.3 mmol) followed by AlCl3 (438 mg, 3.3 mmol). To this solution was added dropwise a solution of ethyl (±)-10,11-dihydro-3-methoxy-2-methyl-5H-dibenzo[a,d]cycloheptene-10-acetate (200 mg, 0.6 mmole) in dry CH2Cl2 (6 mL), and the resulting mixture was stirred at RT for 2 hr. The reaction was quenched with 1.0 N HCl (10 mL), and the layers were separated. The organic layer was dried (MgSO4) and concentrated on the rotavap to give the title compound (100 mg, 56%) as a colorless oil: MS (ES) m/e 311.2 (M+H)+.