Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([OH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]CC.[C:20](OCC)(=[O:24])[CH:21]([CH3:23])[OH:22]>>[C:20]([O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])(=[O:24])[CH:21]([CH3:23])[OH:22]
Reactant: CCOC(=O)C(C)O
Reactant: CCCCCCCCCCCCCCCCCCO
Product: CCCCCCCCCCCCCCCCOC(=O)C(C)O
Temperature: 60 °C
Yield: 42.6 %

Procedure:
A mixture of Novozym® 435 (2.43 g), molecular sieves (20.17 g), 1-octadecanol (4.04 g), and ethyl lactate (8.86 g) in a 150 mL beaker was maintained at 60° C. in a convection oven for 28 hours. Upon work-up, 2.0 g of cetyl lactate (40% yield) was obtained as a waxy white solid. The purity of the product was >98% as assessed by HPLC-RI.
Reaction SMILES: [CH2:1]([O:3][P:4]([C:9]([C:12]1[CH:21]=[C:20]2[C:15]([CH:16]=[CH:17][C:18](/[CH:22]=[N:23]/O)=[N:19]2)=[CH:14][C:13]=1[Br:25])([F:11])[F:10])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>C(#N)C>[CH2:1]([O:3][P:4]([C:9]([C:12]1[CH:21]=[C:20]2[C:15]([CH:16]=[CH:17][C:18]([C:22]#[N:23])=[N:19]2)=[CH:14][C:13]=1[Br:25])([F:10])[F:11])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]
Reactant: CCOP(=O)(OCC)C(F)(F)c1cc2nc(/C=N/O)ccc2cc1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: ClC(Cl)(Cl)Cl
Product: CCOP(=O)(OCC)C(F)(F)c1cc2nc(C#N)ccc2cc1Br
Temperature: 100 °C
Reaction time: 1 h

Procedure:
To a stirred solution of diethyl[(6-bromo-2-[(E)-(hydroxyimino)methyl]quinolin-7-yl)(difluoro)methyl]phosphonate (520 mg, 1.189 mmol) in acetonitrile (30 mL) at room temperature were added triphenylphosphine (1.248 g, 4.76 mmol) and carbon tetrachloride (230 μL, 2.383 mmol). The reaction mixture was stirred at 100° C. for 1 hour. It was concentrated to dryness in vacuo, pre-adsorbed in silica gel for flash chromatography eluting with ethyl acetate in toluene (20% to 30%) to afford diethyl[(6-bromo-2-cyanoquinolin-7-yl)(difluoro)methyl]phosphonate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:26])[CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24]Cl)=[CH:20][CH:19]=3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:27][NH:28][CH2:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:26])[CH2:16][CH2:17][C:18]3[CH:19]=[CH:20][C:21]([CH2:24][N:28]([CH3:27])[CH2:29][C:30]4[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=4)=[CH:22][CH:23]=3)=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: CNCc1ccncc1
Reactant: O=C(CCc1ccc(CCl)cc1)Nc1ccc(-c2ccc(Cl)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CN(Cc1ccncc1)Cc1ccc(CCC(=O)Nc2ccc(-c3ccc(Cl)cc3)cc2)cc1
Reaction time: 24 h

Procedure:
A reaction mixture of 70 mg (0.18 mmol) of N-(4′-chlorobiphenyl-4-yl)-3-(4-chloromethylphenyl)propionamide, 18 mg (0.15 mmol) of methylpyridin-4-ylmethylamine, and 41 mg (0.3 mmol) of potassium carbonate in 5 mL of acetone is agitated for 24 hours at reflux temperature. The reaction mixture is evaporated down. The residue is triturated with water and diisopropyl ether, suction filtered and dried in the air. Yield: 52 mg (87% of theory); melting point: 102° C.; C29H28ClN3O (M=470.01); calc.: molecular ion peak (M+H)+: 470/72 (Cl); found: molecular ion peak (M+H)+: 470/72 (Cl).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[S:21][CH2:22][CH3:23].[OH:24]O>CO.C(O)(C)C>[NH2:1][C:2]1[N:6]([C:7]2[C:8]([Cl:18])=[CH:9][C:10]([C:14]([F:17])([F:15])[F:16])=[CH:11][C:12]=2[Cl:13])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[S:21]([CH2:22][CH3:23])=[O:24]
Reactant: CCSc1c(C#N)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Reactant: OO
Solvent: CC(C)O
Solvent: CO
Product: CCS(=O)c1c(C#N)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Temperature: 60 °C
Reaction time: 2 h
Yield: 79.4 %

Procedure:
To a solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthiopyrazole (22.25 g) in methanol was added a solution of sulfuiric acid (1.5 g) in isopropanol. Hydrogen peroxide (6.95 g of 30% aqueous solution) was added and the temperature raised to 60° C. After two hours, the reaction was filtered and the solid washed with methanol. The filtrate was washed (water), dried and recrystallized (methanol) to give 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulfinylpyrazole (18.4 g), m.p. 173-174° C.
Reaction SMILES: [CH3:1][S:2]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH2:14]O)[CH:12]=2)[CH:7]=[CH:6]1)(=[O:4])=[O:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:36]>C(Cl)Cl>[CH3:1][S:2]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH2:14][Br:36])[CH:12]=2)[CH:7]=[CH:6]1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)n1ccc2ccc(CO)cc21
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CS(=O)(=O)n1ccc2ccc(CBr)cc21
Temperature: 25 °C
Reaction time: 4 h
Yield: 66.6 %

Procedure:
A solution of N-methanesulfonyl-6-hydroxymethylindole (340 mg, 1.51 mmol, from above) and triphenylphosphine (Ph3P) (415 mg, 1.58 mmol) in 5 ml of dry CH2Cl2 was cooled to 0° C. and a solution of carbon tetrabromide (551 mg, 1.66 mmol) in 3 ml dry CH2Cl2 was added dropwise via cannula (2 ml CH2Cl2 rinse). The reaction mixture was allowed to warm to room temperature. After 4 hr, the solvent was removed by rotary evaporation and the resultant purple oil was purified by flash column chromatography (silica gel, 20% ethyl acetate/hexane) to give 290 mg of N-methanesulfonyl-6-bromomethylindole, a colorless oil which solidified on standing (67% yield).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12](=O)[N:13]=1.[NH:19]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)[NH2:20]>CO>[CH:16]1[CH:17]=[CH:18][C:10]([OH:9])=[C:11]([C:12]2[N:13]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[OH:1])[N:19]([C:21]3[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=3)[N:20]=2)[CH:15]=1
Reactant: O=c1nc(-c2ccccc2O)oc2ccccc12
Reactant: NNc1ccc(C(=O)O)cc1
Solvent: CO
Product: O=C(O)c1ccc(-n2nc(-c3ccccc3O)nc2-c2ccccc2O)cc1
Temperature: 27.5 °C
Reaction time: 0.17 h
Yield: 79 %

Procedure:
A mixture of methanol (450.0 ml), 2-(2-hydroxyphenyl)-benz[1,3]oxazin-4-one (30.0 gm) were stir for 10 min at 25-30° C. To the above contents 4-hydrazino benzoic acid (20.03 gm) was added. The contents were heated to reflux temperature 65-70° C. The contents were maintained for 4 hours at 65-70° C. The reaction mass was cooled Slowly to 0-5° C. and maintained it for 1 hour at 0-5° C. The reaction mass was filtered and washed with methanol (30.0 ml). Compound was taken into methylene chloride and stir for 10 min 25-30° C. The contents were heated to reflux temperature (40-45° C.) and maintained the contents for 1 hr at reflux temperature. Cool the contents to 25-30° C. and stirred for 1 hr at 25-30° C. The reaction mass was filtered and washed with methylene chloride (30.0 ml). Dried the compound at 60-65° C. Yield: 79.0%.
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)(C)(C)C.[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26]>ClCCl>[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26].[O:15]([CH2:14][C@H:11]1[CH2:12][CH2:13][C@H:8]([NH2:7])[CH2:9][CH2:10]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](COc2ccccc2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@H]1CC[C@H](COc2ccccc2)CC1
Reaction time: 2 h

Procedure:
380 mg of (trans-4-phenoxymethyl-cyclohexyl)-carbamic acid tert-butyl ester is dissolved in 5 mL of dichloromethane and 5 ml of trifluoroacetic acid is added. The mixture is stirred for 2 h, concentrated in vacuo and stripped twice from dichloromethane to afford 250 mg of trans-4-phenoxymethylcyclohexylamine trifluoroacetate as a white solid.
Reaction SMILES: C(OC([NH:8][C:9]1[CH:10]=[C:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[S:12][C:13]=1[C:14]#[C:15][Si](C)(C)C)=O)(C)(C)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-]>C1COCC1>[S:12]1[C:13]2[CH:14]=[CH:15][NH:8][C:9]=2[CH:10]=[C:11]1[C:20]([O:22][CH2:23][CH3:24])=[O:21]
Reactant: CCOC(=O)c1cc(NC(=O)OC(C)(C)C)c(C#C[Si](C)(C)C)s1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CCOC(=O)c1cc2[nH]ccc2s1
Yield: 94 %

Procedure:
A solution (0.3 M) of ethyl 4-[(tert-butoxycarbonyl)amino]-5-[(trimethylsilyl)ethynyl]thiophene-2-carboxylate in THF was treated with n-Bu4NF (2 eq.). The mixture was irradiated in a microwave apparatus at 120° C. for 20 min. Evaporation of the solvent gave a residue that was purified by flash chromatography on silica gel (1:3 AcOEt/petroleum ether) to afford the title compound (94%) as a solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]([CH3:10])[C:8]#[N:9].C(O)(C)(C)C.[C:16]([O:20][CH3:21])(=[O:19])[CH:17]=[CH2:18]>O>[C:8]([C:7]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)([CH3:10])[CH2:18][CH2:17][C:16]([O:20][CH3:21])=[O:19])#[N:9]
Reactant: CC(C#N)c1ccccn1
Reactant: C=CC(=O)OC
Solvent: O
Solvent: CC(C)(C)O
Product: COC(=O)CCC(C)(C#N)c1ccccn1
Yield: 41.8 %

Procedure:
To a dried flask under nitrogen was added 2-(2-pyridinyl)-propanenitrile (Preparation 43, 6.26 g, 47.4 mmol), t-butanol (30 ml), Triton B (6.66 g, 39.8 mmol) and methyl acrylate (6.12 g, 71.1 mmol). The reaction mixture was heated at reflux for 2.5 h. The solid was removed, and the filtrate concentrated in vacuo to give a yellow oil. Water (30 ml) was added and the product was extracted with diethyl ether. The organic extracts were dried (Na2SO4) and concentrated in vacuo to give a light yellow oil (4.32 g, 42%).
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH2:10][C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[O:12])=[CH:4][C:3]=2[O:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1>[CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH:10]([CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[O:12])=[CH:4][C:3]=2[O:2]1
Reactant: CC(C)c1ccc(S(=O)(=O)NC(=O)Cc2ccc3c(c2)OCO3)cc1
Reactant: BrCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)c1ccc(S(=O)(=O)NC(=O)C(Cc2ccccc2)c2ccc3c(c2)OCO3)cc1
Temperature: -78 °C
Yield: 64.3 %

Procedure:
A solution of 0.228 g (0.63 mmol) of the product of Example 1 was dissolved in 0.5 mL of anhydrous THF in an oven dried 25 mL round bottom flask and was magnetically stirred at -78° C. under a nitrogen atmosphere. A solution of lithium bis(trimethylsilyl)amide (1.89 mL; 1.0M; 1.89 mmol) was slowly added and the resulting yellow solution was stirred at -78° C. for 1 hour. At this point 150 μL (1.26 mmol) of benzyl bromide was added via syringe, the dry ice-acetone bath was removed, the reaction mixture was allowed to warm to room temperature and was stirred an additional 2 hours. The mixture was then partitioned between EtOAc and 10% aqueous NaHSO4 and extracted. The organic layer was separated, washed once with water, once with saturated brine, dried (MgSO4), filtered and evaporated. The residue was purified on a silica gel flash chromatography column eluted with CHCl3 -MeOH--NH4OH (92:8:0.5). Evaporation of the purified fractions and drying in vacuo afforded 0.183 g (64%) of the title compound.
Reaction SMILES: Cl.[C:2]1([NH:8][CH:9]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:10]([OH:12])=[O:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:43]12[CH2:50][CH2:49][CH:46]([CH2:47][CH2:48]1)[C@@H:45](O)[CH2:44]2>C1COCC1>[C:2]1([NH:8][CH:9]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:10]([O:12][C@@H:45]2[CH:46]3[CH2:49][CH2:50][N:43]([CH2:48][CH2:47]3)[CH2:44]2)=[O:11])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O[C@H]1CN2CCC1CC2
Reactant: O=C(O)C(Nc1ccccc1)c1cccs1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Product: O=C(O[C@H]1CN2CCC1CC2)C(Nc1ccccc1)c1cccs1
Temperature: 25 °C
Reaction time: 16 h
Yield: 7.2 %

Procedure:
2-(Phenylamino)-2-(thiophen-2-yl)acetic acid hydrochloride (I29) (359 mg, 1.33 mmol), DCC (330 mg, 1.60 mmol), and HOBT (245 mg, 1.60 mmol) were dissolved in THF (15 ml). (R)-quinuclidin-3-ol (339 mg, 2.66 mmol) was added, and the reaction mixture was stirred at room temperature for 16 hours. HOBT (20.4 mg, 0.13 mmol) and DCC (33.0 mg, 0.16 mmol) were added again and the mixture was stirred for additional 8 hours. HOBT (20.4 mg, 0.13 mmol), DCC (33.0 mg, 0.16 mmol), (R)-quinuclidin-3-ol (16.9 mg, 0.13 mmol) were added, and the mixture is stirred for additional 16 hours. THF is evaporated, and the resulting crude oil was dissolved in EtOAc and washed with water and brine. The organic phase was recovered, dried over Na2SO4, filtered and evaporated. The crude was first purified by flash chromatography (DCM/MeOH=9/1) and then by preparative HPLC. The pure fractions were collected and evaporated. The resulting TFA salt was dissolved in THF and passed through a PL-HCO3 cartridge (Varian, 200 mg, 1.8 mmol/g HCO3−). THF was evaporated, and the product was dissolved in dioxane (2 ml) and 4M HCl in dioxane (2 ml) was added. The solvent was evaporated, and the residue was dried under vacuum for 24 hours to obtain the title compound (33 mg, 7% yield, mixture of diastereomers).
Reaction SMILES: [H-].[Na+].[NH:3]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[Br:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]Br.[Cl-].[NH4+]>CN(C)C=O>[Br:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][N:3]([C:4]([O:6][C:7]([CH3:8])([CH3:9])[CH3:10])=[O:5])[C:11](=[O:12])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(C)OC(=O)NC(=O)OC(C)(C)C
Reactant: BrCCCCCCCCBr
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N(CCCCCCCCBr)C(=O)OC(C)(C)C
Reaction time: 1 h
Yield: 69.5 %

Procedure:
Under a nitrogen flow, sodium hydride (40% of mineral oil added; 935 mg, 17 mmol) was suspended in N,N-dimethylformamide (160 mL) and, under ice-water cooling, di-tert-butyl iminodicarboxylate (3.26 g, 15 mmol) was added. After stirring under ice-water cooling for 1 hour, a solution of 1,8-dibromooctane (8.16 g, 30 mmol) in N,N-dimethylformamide (10 mL) was added and the mixture was stirred for 16 hours while allowing the mixture to return to room temperature. Under ice-water cooling, a saturated aqueous solution of ammonium chloride was added to stop the reaction and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by flash column chromatography to obtain tert-butyl N-(8-bromooctyl)-N-[(tert-butoxy)carbonyl]carbamate (4.26 g).
Reaction SMILES: C([O:4][CH:5]([C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:20])[CH2:16][CH2:17][CH2:18][Cl:19])=[CH:11][CH:10]=1)[CH:6]([CH3:8])[CH3:7])(=O)C.Cl>C(O)C>[Cl:19][CH2:18][CH2:17][CH2:16][C:15]([C:12]1[CH:11]=[CH:10][C:9]([CH:5]([OH:4])[CH:6]([CH3:7])[CH3:8])=[CH:14][CH:13]=1)=[O:20]
Reactant: CC(=O)OC(c1ccc(C(=O)CCCCl)cc1)C(C)C
Agent: Cl
Solvent: CCO
Product: CC(C)C(O)c1ccc(C(=O)CCCCl)cc1
Yield: 90 %

Procedure:
Mix 2-(4-(4-chloro-1-oxobutyl)-phenyl-2-methyl propanol acetate, concentrated hydrochloric acid (555 mL), and ethanol (2.5) and reflux for 2.5 hours under a nitrogen atmosphere. Evaporate the solvent in vacuo and take the residue up in methylene chloride (1L). Wash sequentially with water (2×400 mL), aqueous potassium carbonate (10%, 200 mL) and water (300 mL). Evaporate the solvent in vacuo to give the title compound as a light-brown oil (200 g, 90%).
Reaction SMILES: [NH2:1][CH2:2][C:3]([C@@H:5]1[C@@H:10]([OH:11])[C@H:9]([OH:12])[C@@H:8]([CH2:13][OH:14])[O:7][C@@:6]1([NH2:41])[N:15]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:16](=[O:28])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:4].[C:42]([NH:52][C@H:53]([C:61](O)=[O:62])[CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:43].N>ClCCl.CO>[C:42]([NH:52][C@H:53]([C:61]([NH:1][CH2:2][C:3]([C@@H:5]1[C@@H:10]([OH:11])[C@H:9]([OH:12])[C@@H:8]([CH2:13][OH:14])[O:7][C@@:6]1([NH2:41])[N:15]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:16](=[O:28])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:4])=[O:62])[CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:43]
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)O)OCc1ccccc1
Reactant: CCCCCCCCCCCCN(C(=O)CCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)CN
Agent: N
Solvent: CO
Solvent: ClCCl
Product: CCCCCCCCCCCCN(C(=O)CCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Yield: 53 %

Procedure:
from N-(2-glycyl-amino-2-deoxy-β-D-glucopyranosyl)-N-dodecyl-dodecanamide and N-carbobenzoxy-L-phenylalanine. Yield 53%. Rf 0.29 (dichloromethane/methanol/conc. ammonia 15:1:0.1).
Reaction SMILES: [CH3:1][C:2]1[C:11]([S:12][CH3:13])=[CH:10][CH:9]=[CH:8][C:3]=1[NH:4][CH2:5][CH:6]=[O:7].C(=O)([O-])[O-].[Na+].[Na+].C1C=CC=CC=1.[Cl:26][CH2:27][C:28](Cl)=[O:29]>O>[Cl:26][CH2:27][C:28]([N:4]([CH2:5][CH:6]=[O:7])[C:3]1[CH:8]=[CH:9][CH:10]=[C:11]([S:12][CH3:13])[C:2]=1[CH3:1])=[O:29]
Reactant: CSc1cccc(NCC=O)c1C
Reactant: O=C(Cl)CCl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: c1ccccc1
Product: CSc1cccc(N(CC=O)C(=O)CCl)c1C
Temperature: 25 °C

Procedure:
The dimethyl acetal of 2-(2-methyl-3-methylthioanilino)acetaldehyde (0.1 mole), sodium carbonate (0.06 mole) dissolved in water (50 ml) and benzene (50 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and cooling means. The mixture is cooled to a temperature of about 0°C and α-chloroacetyl chloride (0.11 mole) is incrementally added with stirring. After the addition is completed stirring is continued and the reaction mixture is permitted to warm to room temperature. After this time the mixture is filtered, washed with dilute hydrochloric acid and stripped of solvent to yield the desired product the dimethyl acetal of 2-(N-α-chloroacetyl-2-methyl-3-methylthioanilino)acetaldehyde.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C@H:6]([C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=1)[CH2:7][OH:8])=[O:4].[H-].[Na+].[NH4+].[Cl-]>C1COCC1>[F:16][C:11]1[CH:10]=[C:9]([C@H:6]2[NH:5][C:3](=[O:4])[CH2:2][O:8][CH2:7]2)[CH:14]=[C:13]([F:15])[CH:12]=1
Reactant: O=C(CCl)N[C@@H](CO)c1cc(F)cc(F)c1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: O=C1COC[C@@H](c2cc(F)cc(F)c2)N1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2-chloro-N-[(1R)-1-(3,5-difluorophenyl)-2-hydroxyethyl]acetamide from Step C (840 mg, 3.37 mmol) in THF (75 mL) at 0° C. was added NaH (291 mg of a 60% dispersion in oil, 7.28 mmol) and the mixture was stirred at ambient temperature for 1 h. Saturated aqueous NH4Cl (10 mL) was added and the mixture was extracted with EtOAc (2×20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—75:25 to 25:75, to give the title compound. MS: m/z=214 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=3)[CH:11]=[CH:10][C:9]=2[N+:23]([O-])=O)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C>C1COCC1.[Pt]>[Br:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]2[C:9]([NH2:23])=[CH:10][CH:11]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=3)[CH:13]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(COc2ccc([N+](=O)[O-])c(NCc3ccc(Br)cc3)c2)nc1
Agent: [Pt]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Cc1ccc(COc2ccc(N)c(NCc3ccc(Br)cc3)c2)nc1
Reaction time: 6 h

Procedure:
To a solution of N-(4-bromobenzyl)-5-((5-methylpyridin-2-yl)methoxy)-2-nitroaniline (4.1 g, 9.6 mmol) in THF (75 mL) was added DIPEA (0.8 mL, 4.8 mmol) followed by 5% platinum on carbon (0.4 g, 2.1 mmol). The reaction vessel was evacuated and then placed under 1 atmosphere of H2 for 6 h. The mixture was then flushed with N2 and filtered through a pad of Celite. The Celite was rinsed with THF. The resulting filtrate was concentrated to dryness to afford the title compound, which was used without further purification. MS (ESI): mass calcd. for C22H26BrN3O, 397.08; m/z found, 398.0 [M+H]+.
Reaction SMILES: C([O:3][P:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([F:43])([F:42])[C:32]([F:41])([F:40])[C:33]([F:39])([F:38])[C:34]([F:37])([F:36])[F:35])([O:6]CC)=[O:5])C.Br[Si](C)(C)C>ClCCl>[P:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([F:42])([F:43])[C:32]([F:40])([F:41])[C:33]([F:38])([F:39])[C:34]([F:35])([F:36])[F:37])([OH:6])([OH:5])=[O:3]
Reactant: CCOP(=O)(CCCCCCCCCCCCCCCCCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)OCC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Product: O=P(O)(O)CCCCCCCCCCCCCCCCCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reaction time: 18 h
Yield: 63.5 %

Procedure:
To a solution of 1.05 g of 1-(diethylphosphono)-22-(nonafluorobutyl)docosane in 10 mL of dichloromethane was added 0.61 g of bromotrimethylsilane. After 18 hr at room temperature, the solution was concentrated to a beige grease to which was added 30 mL of methanol. A white solid formed, and the resultant mixture was stirred at room temperature for 30 min. Removal of the solvent under reduced pressure left a white solid, which was slurried with an additional 20 mL of methanol for 30 min. Removal of solvent again left a white solid, and recrystallization of the crude product from methanol provided 0.61 g of 1-phosphono-22-(nonafluorobutyl)docosane (CF3(CF2)3(CH2)22PO3H2) as white crystals, m.p. 106-108° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([F:14])[C:5]2[O:9][C:8](C(O)=O)=[CH:7][C:6]=2[CH:13]=1>N1C2C(=CC=CC=2)C=CC=1.[Cu]>[Br:1][C:2]1[CH:3]=[C:4]([F:14])[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:13]=1
Reactant: O=C(O)c1cc2cc(Br)cc(F)c2o1
Agent: [Cu]
Solvent: c1ccc2ncccc2c1
Product: Fc1cc(Br)cc2ccoc12
Yield: 102.2 %

Procedure:
A solution of 5-bromo-7-fluoro-1-benzofuran-2-carboxylic acid (1.274 mmol) in quinoline (2 mL) was treated with copper dust (0.236 mmol). The reaction was purged with nitrogen, sealed and irradiated in a microwave reactor at 230° C. for 60 min. The solution was diluted with ethyl acetate and was filtered through Celite. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography (hexanes) to provide the title compound as a clear oil (280 mg, 100% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.17 (d, J=2.02 Hz, 1H) 7.77 (d, J=1.77 Hz, 1H) 7.55 (dd, J=10.48, 1.64 Hz, 1H) 7.07 (dd, J=3.16, 2.15 Hz, 1H).