Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[NH:7][N:6]=[C:5]2[CH3:12].O1CCOCC1.[C:19](=O)([O-:21])[O-:20].[Na+].[Na+]>O>[Cl:11][C:9]1[CH:10]=[C:2]([C:19]([OH:21])=[O:20])[CH:3]=[C:4]2[C:8]=1[NH:7][N:6]=[C:5]2[CH3:12]
Reactant: Cc1n[nH]c2c(Cl)cc(Br)cc12
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: Cc1n[nH]c2c(Cl)cc(C(=O)O)cc12
Temperature: 165 °C
Reaction time: 0.01 h
Yield: 80.4 %

Procedure:
A microwave tube was charged with 5-bromo-7-chloro-3-methyl-1H-indazole (610 mg, 2.48 mmol), dioxane (5 mL), Hermann's catalyst (119 mg, 0.12 mmol) and a solution of sodium carbonate (790 mg, 7.46 mmol) in water (10 mL). The mixture was stirred for 20 sec, heated at 165° C. for 30 minutes in a microwave reactor at very high absorption setting. The reaction was vented before handling. The mixture was filtered through diatomaceous earth and washed with EtOAc. The filtrate was concentrated, the residue was dissolved in water and acidified to pH ˜3 with conc HCl. The solids were collected by filtration and dried to afford the title compound (420 mg, 82%).
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=3)[CH:10]=2)=[CH:5][CH:4]=1.[OH-].[Na+].O1CCCC1.Cl>O.CO>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=3)[CH:10]=2)=[CH:7][CH:8]=1
Reactant: COC(=O)c1ccc(-c2cc(-c3ccc(C(F)(F)F)cc3)on2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1ccc(-c2cc(-c3ccc(C(F)(F)F)cc3)on2)cc1
Temperature: 60 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
A mixture of methyl 4-[5-(4-trifluoromethylphenyl)-3-isoxazolyl]benzoate (0.486 g), 1 M aqueous sodium hydroxide solution (4 ml), tetrahydrofuran (20 ml) and methanol (20 ml) was stirred at 60° C. for 1 hr. After cooling, the reaction mixture was poured into water and 1 M hydrochloric acid (15 ml) was added. The crystals were collected by filtration and recrystallized from ethanol to give 4-[5-(4-trifluoromethylphenyl)-3-isoxazolyl]benzoic acid (0.358 g, yield 77%) as a colorless crystalline powder. melting point: >300° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(N(C(C)C)C(C)C)C.ClC([O:28][C:29](Cl)(Cl)Cl)=O.[C:33]1([CH:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][C:29]([N:42]3[CH2:43][CH2:44][CH:39]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:40][CH2:41]3)=[O:28])=[CH:13][CH:14]=2)=[N:6][CH:7]=1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: c1ccc(C2CCNCC2)cc1
Reactant: Cc1ccc(Cc2ccc(O)cc2)nc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1ccc(Cc2ccc(OC(=O)N3CCC(c4ccccc4)CC3)cc2)nc1
Temperature: -30 °C
Reaction time: 0.17 h
Yield: 28 %

Procedure:
To a solution of 4-(5-methyl-pyridin-2-ylmethyl)phenol (0.8 mmol) prepared as described above and ethyldiisopropylamine (1.5 mmol) in CH2Cl2 (5 mL) at −30° C. was added trichloromethyl chloroformate (1.0 mmol). The solution was stirred at −30° C. for 10 min and at reflux temperature for 2 h. The solution was evaporated to dryness and redissolved in CH2Cl2 (5 mL) and cooled to 0° C. before addition of 4-phenylpiperidine (1.5 mmol). The solution was stirred at room temperature for 16 h evaporated to give the crude product which was purified by FC (Quad flash 40 CH2Cl2:Et2O:Heptane:Et3N 1:1:2:0.25->1:1:1:0.25) to give the title compound in 28% yield as an oil.
Reaction SMILES: [OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:17])[C:3]=1[C:18]([O:20]C)=O.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1>>[OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:15])(=[O:16])[N:4]([CH3:17])[C:3]=1[C:18]([NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)=[O:20]
Reactant: COC(=O)C1=C(O)c2sc3ccccc3c2S(=O)(=O)N1C
Reactant: Nc1ccccn1
Product: CN1C(C(=O)Nc2ccccn2)=C(O)c2sc3ccccc3c2S1(=O)=O
Yield: 52 %

Procedure:
Prepared analogous to Example 1 from methyl 4-hydroxy-2-methyl-2H-[1]-benzothieno[2,3-e]-1,2-thiazine-3-carboxylate-1,1-dioxide and 2-amino-pyridine with a yield of 52% of theory.
Reaction SMILES: [CH2:1]([N:8]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH:9]1[CH2:15][CH2:14][CH:13]2[CH2:16][CH:10]1[C:11](=[O:24])[N:12]2[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>C1COCC1.O>[CH2:25]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@H:9]1[CH2:15][CH2:14][C@@H:13]([NH:12][C:17](=[O:18])[O:19][C:20]([CH3:22])([CH3:23])[CH3:21])[CH2:16][C@H:10]1[CH2:11][OH:24])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1C(=O)C2CC1CCC2N(Cc1ccccc1)Cc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H]1CC[C@H](N(Cc2ccccc2)Cc2ccccc2)[C@H](CO)C1
Temperature: 25 °C
Reaction time: 6 h
Yield: 72.4 %

Procedure:
Examples 11p and 11q, Step 3: To a solution of tert-butyl 2-(dibenzylamino)-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate (3.12 g, 7.42 mmoles) in 50 ml of THF and 10 ml of water was added sodium borohydride (1.4 g, 37.1 mmoles), and the mixture was stirred for 6 hours at room temperature. The reaction was quenched with saturatedd sodium bicarbonate, and the product was extracted with EtOAc three times. The combined extracts were washed with brine, dried over Na2SO4 and evaporated to give an oily residue. It was purified by column chromatography (silica gel, 3:7 EtOAc and hexane) to give 2.28 g of tert-butyl (1R,3R,4S)-4-(dibenzylamino)-3-(hydroxymethyl)cyclohexylcarbamate as an oil.
Reaction SMILES: [C:1](OC(=O)C)(=O)[CH3:2].[NH2:8][C:9]1[C:14]([NH2:15])=[CH:13][C:12]([N+:16]([O-:18])=[O:17])=[CH:11][N:10]=1>C(O)(=O)C>[CH3:1][C:2]1[NH:8][C:9]2=[N:10][CH:11]=[C:12]([N+:16]([O-:18])=[O:17])[CH:13]=[C:14]2[N:15]=1
Reactant: CC(=O)OC(C)=O
Reactant: Nc1cc([N+](=O)[O-])cnc1N
Solvent: CC(=O)O
Product: Cc1nc2cc([N+](=O)[O-])cnc2[nH]1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 23.1 %

Procedure:
2.3 mL (24.33 mol) of acetic anhydride are added to a solution, stirred at 15° C., of 1.5 g (9.73 mmol) of 2,3-diamino-5-nitropyridine in 15 mL of acetic acid. After stirring for 15 minutes at room temperature, the mixture is heated at 110° C. for 2 hours and then at 140° C. for 7 hours. The resulting mixture is concentrated under reduced pressure and taken up in 100 mL of water. A precipitate is collected by filtration. After purification by chromatography on a column of silica, 0.4 g of the expected product is obtained.
Reaction SMILES: [CH2:1]([C:3]1[C:11]2[O:10][C:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18]C)=[CH:14][CH:13]=3)=[CH:8][C:7]=2[CH:6]=[C:5]([O:20]C)[CH:4]=1)[CH3:2].N1C(=O)CC[C@H]1C(O)=O.Cl.OC1C=C(C(C)C#N)C2OC(C3C=CC(O)=CC=3)=CC=2C=1>>[CH2:1]([C:3]1[C:11]2[O:10][C:9]([C:12]3[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=3)=[CH:8][C:7]=2[CH:6]=[C:5]([OH:20])[CH:4]=1)[CH3:2]
Reactant: CCc1cc(OC)cc2cc(-c3ccc(OC)cc3)oc12
Agent: CC(C#N)c1cc(O)cc2cc(-c3ccc(O)cc3)oc12
Agent: Cl
Agent: O=C1CC[C@@H](C(=O)O)N1
Product: CCc1cc(O)cc2cc(-c3ccc(O)cc3)oc12

Procedure:
Compound 30 was prepared by demethylation of 29 using Pyr-HCl (method described previously for preparation of 21): Mp=218–220° C.; 1H NMR (DMSO-d6) δ 9.81 (s, 1 H), 9.02 (s, 1 H), 7.69 (d, 2 H, J=8.5 Hz), 6.99 (s, 1H), 6.86 (d, 2 H, J=8.5 Hz), 6.70 (d, 1 H, J=2.2 Hz), 6.55 (d, 1 H, J=2.0 Hz), 2.81 (q, 2 H, J=7.5 Hz), 1.29 (t, 3 H, J=7.5 Hz); MS 255 (M+H)+
Reaction SMILES: [CH:1]1[C:6]([C:7](OO)=O)=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OOC(=O)C1C=CC=CC=1)(=[O:18])C1C=CC=CC=1.[CH2:29]([C:32]1C=CC(C)=CC=1)[CH:30]=C>C(Cl)(Cl)Cl>[CH3:30][CH:29]=[CH:32][CH2:7][C:6]1[CH:5]=[CH:4][CH:3]2[O:18][CH:2]2[CH:1]=1
Reactant: C=CCc1ccc(C)cc1
Reactant: O=C(OO)c1ccccc1
Reactant: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)Cl
Product: CC=CCC1=CC2OC2C=C1
Reaction time: 96 h
Yield: 47.5 %

Procedure:
To chloroform solution containing perbenzoic acid prepared from 36.6 g of benzoyl peroxide was added, with ice-cooling, 6.6 g of p-allyltoluene dissolved in 20 ml of chloroform. The resulting mixture was allowed to stand at 5° C for 4 days and washed with 10% sodium hydroxide solution, water, Mohr's salt solution and then water, and dried over anhydrous sodium sulfate. The solvent was evaporated to obtain the residue, which was distilled under reduced pressure to give 35.3 g (yield 47.5%) of p-methylallylbenzene oxide as colourless liquid having a boiling point of 92° C/7 mmHg.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[CH3:9])[NH2:5].[CH3:10][S:11](Cl)(=[O:13])=[O:12].CCOC(C)=O>N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][S:11]([CH3:10])(=[O:13])=[O:12])[CH:6]=[CH:7][C:8]=1[CH3:9]
Reactant: Cc1ccc(N)cc1Br
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: Cc1ccc(NS(C)(=O)=O)cc1Br
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.1 %

Procedure:
A cooled (0° C.) solution of 3-bromo-4-methylaniline (ABCR; 1.00 g; 5.37 mmol) in pyridine (20 ml) was treated with methanesulfonyl chloride (500 μl; 6.45 mmol). The reaction mixture was allowed to warm to RT and stirred for 1 hour, then EtOAc was added and the organic layer was washed with a 1N aqueous solution of HCl. The organic layer was dried over MgSO4, filtered and concentrated to dryness to give the title compound as a brown solid (1.42 g, quantitative).
Reaction SMILES: [Br:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][CH2:7][CH:8]([OH:34])[CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]([O:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)[CH2:18][CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.I[CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]>C1COCC1.CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH:8]([O:34][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]([O:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)[CH2:18][CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:13][CH:12]=2)=[CH:35][CH:36]=1
Reactant: OC(COc1ccc(Br)cc1)COc1ccc(C(CCCc2ccccc2)OC2CCCCO2)cc1
Reactant: CCCCCI
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CCCCCOC(COc1ccc(Br)cc1)COc1ccc(C(CCCc2ccccc2)OC2CCCCO2)cc1

Procedure:
A mixture of the product (0.57 g) of Step 3, 0.3 mL of 1-iodopentane and 80 mg of Nail in 20 ml of 1:1 THF/DMF was refluxed for 4 hrs. The mixture was then quenched with 5 mL of MeOH, 20 mL of Sat. NH4Cl, and extracted with 50 mL of Et2O. The extract was dried over NaSO4 and concentrated. The residue was purified by flash chromatography eluted with EtOAc and hexanes (7:1) to give 0.6 g of the title compound.
Reaction SMILES: Cl(O)(=O)(=O)=O.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[C@@H:20]([OH:21])[C:19](=[O:22])[N:18]([CH2:23][CH2:24][N:25]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH3:26])[C:17]3[CH:34]=[CH:35][C:36]([CH3:38])=[CH:37][C:16]=3[S:15]2)=[CH:10][CH:9]=1.[C:39](OC(=O)C)(=[O:41])[CH3:40]>N1C=CC=CC=1>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[C@@H:20]([O:21][C:39](=[O:41])[CH3:40])[C:19](=[O:22])[N:18]([CH2:23][CH2:24][N:25]([CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH3:26])[C:17]3[CH:34]=[CH:35][C:36]([CH3:38])=[CH:37][C:16]=3[S:15]2)=[CH:10][CH:9]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc([C@@H]2Sc3cc(C)ccc3N(CCN(C)Cc3ccccc3)C(=O)[C@@H]2O)cc1
Agent: [O-][Cl+3]([O-])([O-])O
Solvent: c1ccncc1
Product: COc1ccc([C@@H]2Sc3cc(C)ccc3N(CCN(C)Cc3ccccc3)C(=O)[C@@H]2OC(C)=O)cc1
Temperature: 100 °C

Procedure:
10.7 g of (-)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(N-benzyl-N-methylamino)ethyl]-8-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one perchlorate is converted to its free base, and 80 ml of acetic anhydride and one ml of pyridine are added thereto. The mixture is heated at 100° C. for 4 hours. The mixture is evaporated under reduced pressure to remove acetic anhydride and pyridine. Benzene is added to the residue, and the mixture is evaporated under reduced pressure to remove solvent. 10.37 g of (-)-cis-2-(4-methoxyphenyl)-3-acetoxy-5-[2-(N-benzyl-N-methylamino)ethyl]-8-methyl- 2,3-dihydro-1,5-benzothiazepin-4(5H)-one are obtained as an oil.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:33])[CH2:10][CH2:11][C@H:12]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:13](=[O:24])[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:35][OH:36].CCN(C(C)C)C(C)C>C(O)C>[CH2:1]([O:8][C:9](=[O:33])[CH2:10][CH2:11][C@H:12]([NH:25][C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[C:13](=[O:24])[NH:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:22](=[NH:23])[NH:35][OH:36])=[CH:20][CH:21]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NO
Reactant: CC(C)(C)OC(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)NCc1ccc(C#N)cc1
Agent: Cl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)NCc1ccc(C(=N)NO)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 152.7 %

Procedure:
A solution of compound Q (9.65 g, 20.0 mmol), hydroxylamine hydrochloride (2.10 g, 30.0 mmol) and DIEA (5.22 ml, 30.0 mmol) in ethanol (abs., 150 ml) was refluxed for 6 h. The reaction mixture was allowed to cool to room temperature and stirred for additional 16 h, then the solvents were evaporated in vacuo. The resultant residue was dried in vacuo to provide compound R (14.8 g, yield exceeded quantitative) as yellowish oil. LC-MS [M+H] 485.5 (C25H32N4O6+H, calc: 485.8). Compound R was used without further purification.
Reaction SMILES: [CH3:1][O:2][C@@H:3]([C@@H:28]([N:33]([CH3:41])[C:34](=[O:40])[C@H:35]([CH:37]([CH3:39])[CH3:38])[NH2:36])[C@@H:29]([CH3:32])[CH2:30][CH3:31])[CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C@H:12]([O:26][CH3:27])[C@@H:13]([CH3:25])[C:14](=[O:24])[NH:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:6].[C:42]([O:46][C:47]([NH:49][C:50]1([C:54](O)=[O:55])[CH2:53][O:52][CH2:51]1)=[O:48])([CH3:45])([CH3:44])[CH3:43].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C)C=O>[C:42]([O:46][C:47]([NH:49][C:50]1([C:54]([NH:36][C@H:35]([C:34]([N:33]([C@@H:28]([C@@H:29]([CH3:32])[CH2:30][CH3:31])[C@H:3]([O:2][CH3:1])[CH2:4][C:5]([N:7]2[CH2:11][CH2:10][CH2:9][C@H:8]2[C@H:12]([O:26][CH3:27])[C@@H:13]([CH3:25])[C:14](=[O:24])[NH:15][CH2:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:6])[CH3:41])=[O:40])[CH:37]([CH3:39])[CH3:38])=[O:55])[CH2:51][O:52][CH2:53]1)=[O:48])([CH3:45])([CH3:44])[CH3:43]
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)NCCc1ccccc1)OC)N(C)C(=O)[C@@H](N)C(C)C
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)COC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)NCCc1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)C1(NC(=O)OC(C)(C)C)COC1)C(C)C
Reaction time: 16 h
Yield: 104 %

Procedure:
To #73 (100 mg, 0.174 mmol, 1 eq.) in dichloromethane (4 mL, 0.04) and N,N-dimethylformamide (0.5 mL) was added #71 (45.2 mg, 0.208 mmol, 1.2 eq.), followed by diisopropylethylamine (92 μL, 0.521 mmol, 3 eq.) and HATU (102 mg, 0.260 mmol, 1.5 eq.). After 16 hours, the reaction was concentrated in vacuo and the residue was taken up in ethyl acetate (6 mL) and washed with 1 M aqueous hydrochloric acid solution (2×2 mL) and with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by reverse phase chromatography (Method C) to give #74 (140 mg), which was used in the next step without further purification. LC-MS: m/z 774.7 [M+H+], 796.6 [M+Na+], retention time=0.91 minute.
Reaction SMILES: ClCCl.[N+:4]([C:7]1[CH:8]=[CH:9][C:10]([Cl:17])=[C:11]([S:13](Cl)(=[O:15])=[O:14])[CH:12]=1)([O-:6])=[O:5].[CH3:18][NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]>C(N(CC)CC)C>[CH3:18][N:19]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[S:13]([C:11]1[CH:12]=[C:7]([N+:4]([O-:6])=[O:5])[CH:8]=[CH:9][C:10]=1[Cl:17])(=[O:15])=[O:14]
Reactant: CCCCCCCCCCCCCCCCCCNC
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Cl)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCCN(C)S(=O)(=O)c1cc([N+](=O)[O-])ccc1Cl

Procedure:
Dichloromethane (100 ml) was mixed with 44 grams of 5-nitro-2-chlorobenzenesulfonyl chloride and a dichloromethane solution which contained 48.4 grams of methyloctadecylamine and 36.1 ml of triethylamine was added dropwise to the mixture. After the reaction had been completed the reaction solvent was removed by distillation under reduced pressure, 300 ml of methanol was added and a solution was formed by heating. Crystals precipitated out on cooling the solution slowly and these were recovered by filtration and dried.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH:10]=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:17]([O-:20])(=[O:19])[CH3:18].[NH4+:21].C(O)(=O)CC(O)=O>C(O)C>[NH2:21][CH:10]([C:9]1[CH:12]=[CH:13][C:14]([O:15][CH3:16])=[C:7]([O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:8]=1)[CH2:18][C:17]([OH:20])=[O:19]
Reactant: CC(=O)[O-]
Reactant: [NH4+]
Reactant: COc1ccc(C=O)cc1OC1CCCC1
Agent: O=C(O)CC(=O)O
Solvent: CCO
Product: COc1ccc(C(N)CC(=O)O)cc1OC1CCCC1
Temperature: 45 °C
Yield: 60.3 %

Procedure:
A stirred mixture of 3-cyclopentyloxy-4-methoxybenzaldehyde (54.9 grams, 249 mmol) and ammonium acetate (58.2 grams, 748 mmol) in ethanol (200 mL, 95%) was heated to 45° C. To the yellowish suspension, was added malonic acid (25.9 grams, 249 mmol) as a solid. The mixture was refluxed for 16 h. The mixture was cooled to room temperature. The suspension was filtered and the solid was washed with cold ethanol (200 mL) until the color was removed. The white solid was dried in a vacuum oven (45° C., 1 torr) to afford 3-amino-3-(3'-cyclopentoxy-4'-methoxyphenyl)propionic acid as white solid (41.97 grams, 61% yield): mp, 234.0°-235.0° C.; 1H NMR (CDCl3)δ1.62-1.98 (m, 8H, C5H8), 2.53 (d, J=7 Hz, 2H, CH2), 3.80 (s, 3H, CH3), 4.21 (t, J=7 Hz, 1H, OCH), 4.84-4.86 (m, 1H, NCH), 6.96-7.03 (m, 3H, Ar); 13C NMR (CDCl3)δ26.33, 34.97, 49.78, 55.32, 58.48, 83.99, 114.99, 116.04, 121.63, 140.63, 149.12, 150.75, 182.87; Anal Calcd for C15 H21NO4 : C, 64.50; H, 7.58; N, 5.01. Found: C, 64.54; H, 7.68; N, 4.93.
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH:14]([CH:22]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28](Br)=[CH:27][CH:26]=1)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].[Cl:42][C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.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>[Cl:42][C:43]1[CH:48]=[CH:47][C:46]([C:28]2[CH:29]=[CH:30][C:25]([CH2:24][CH2:23][CH:22]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[CH:14]([CH2:13][CH2:12][N:3]3[C:2](=[O:1])[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[C:4]3=[O:11])[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:26][CH:27]=2)=[CH:45][CH:44]=1
Reactant: COc1ccc(COC(CCc2ccc(Br)cc2)C(CCN2C(=O)c3ccccc3C2=O)C(=O)OC(C)(C)C)cc1
Reactant: OB(O)c1ccc(Cl)cc1
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: CN(C)C=O
Solvent: O
Product: COc1ccc(COC(CCc2ccc(-c3ccc(Cl)cc3)cc2)C(CCN2C(=O)c3ccccc3C2=O)C(=O)OC(C)(C)C)cc1
Temperature: 100 °C
Reaction time: 6 h
Yield: 55.2 %

Procedure:
To a solution of the compound (200 mg) obtained from step 7 above, (4-chlorophenyl)boronic acid (90 mg) and potassium carbonate (133 mg) in dimethylformamide (3 ml) was added tetrakis(triphenylphosphine)palladium (0) (18.5 mg) and stirred the reaction mixture for 6 hours at about 100° C. The resulting reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 20% ethyl acetate in hexane as eluant to furnish the title compound (116 mg).
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[CH2:13]([NH2:18])[C:14]([CH3:17])([CH3:16])[CH3:15].[Cl:19][CH2:20][CH2:21][N:22]=[C:23]=[O:24]>>[Cl:19][CH2:20][CH2:21][NH:22][C:23]([N:18]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4])=[O:24]
Reactant: O=C=NCCCl
Reactant: CC(C)(C)CN
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Product: CC(C)(C)CN(C(=O)NCCCl)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Yield: 70.5 %

Procedure:
3.6 g of D-galactose, 3.5 g of neopentylamine and 2.5 g of 2-chloroethyl isocyanate are treated in the same manner as described in Example 5-(1). 5.0 g of 1-(2-chloroethyl)-3-neopentyl-3-D-galactopyranosylurea are thereby obtained as colorless caramel.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[CH:8][C:7]=2/[CH:14]=[CH:15]/[C:16]2[N:17]=[C:18]3[S:25][C:24]([CH3:26])=[C:23]([CH3:27])[N:19]3[C:20](=[O:22])[CH:21]=2)[CH2:3][CH2:2]1.[I:28]N1C(=O)CCC1=O.C1(COC2C(OC)=CC=CC=2/C=C/C2N=C3SC=CN3C(=O)C=2I)CC1>C(#N)C>[CH:1]1([CH2:4][O:5][C:6]2[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[CH:8][C:7]=2/[CH:14]=[CH:15]/[C:16]2[N:17]=[C:18]3[S:25][C:24]([CH3:26])=[C:23]([CH3:27])[N:19]3[C:20](=[O:22])[C:21]=2[I:28])[CH2:3][CH2:2]1
Reactant: COc1cccc(/C=C/c2cc(=O)n3c(C)c(C)sc3n2)c1OCC1CC1
Reactant: O=C1CCC(=O)N1I
Agent: COc1cccc(/C=C/c2nc3sccn3c(=O)c2I)c1OCC1CC1
Solvent: CC#N
Product: COc1cccc(/C=C/c2nc3sc(C)c(C)n3c(=O)c2I)c1OCC1CC1

Procedure:
To a solution of Step 3 intermediate (500 mg, 1.568 mmol) in acetonitrile (10 ml) was added N-iodosuccinimide (494 mg, 2.195 mmol) and reacted according to the procedure described in Step 4, Intermediate 2 to afford 600 mg of the desired compound; 1H NMR (300 MHz, CDCl3) δ 0.32-0.34 (m, 2H), 0.54-0.56 (m, 2H), 1.17-1.20 (m, 1H), 2.29 (s, 3H), 2.58 (s, 3H), 3.75-3.77 (m, 2H), 3.80 (s, 3H), 7.04-7.13 (m, 2H), 7.25-7.27 (m, 1H), 7.47 (d, J=15.9 Hz, 1H), 8.12 (d, J=15.6 Hz, 1H); ESI-MS (m/z) 509.01 (M+H)+.