Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].[OH:9][C:10]1([CH:14]([O:16][C@@H:17]2[CH2:22][CH2:21][C@H:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]5[C:38]([C:43]#[N:44])=[CH:39][CH:40]=[CH:41][CH:42]=5)=[CH:33][CH:32]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]4[N:48]=[CH:49][N:50]=[C:24]34)[CH2:19][CH2:18]2)[CH3:15])[CH2:13][CH2:12][CH2:11]1>CS(C)=O.C(OCC)(=O)C>[OH:9][C:10]1([CH:14]([O:16][C@@H:17]2[CH2:22][CH2:21][C@H:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:32]=[CH:33][C:34]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=5[C:43]5[NH:3][C:4](=[O:7])[O:5][N:44]=5)=[CH:35][CH:36]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]4[N:48]=[CH:49][N:50]=[C:24]34)[CH2:19][CH2:18]2)[CH3:15])[CH2:11][CH2:12][CH2:13]1
Reactant: [NH3+]O
Reactant: O=C([O-])O
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@@H](OC(C)C3(O)CCC3)CC2)c2ncnn12
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n([C@H]2CC[C@@H](OC(C)C3(O)CCC3)CC2)c2ncnn12
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
A mixture of hydroxylammonium chloride (0.92 g), sodium hydrogen carbonate (1.48 g) and dimethyl sulfoxide (3 mL) was stirred at 60° C. for 30 min, a solution of 4′-[(4-{cis-4-[1-(1-hydroxycyclobutyl)ethoxy]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.50 g) in dimethyl sulfoxide (4 mL) was added, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 mL). N,N′-Carbonyldiimidazole (178 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (167 mg) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=60/40→35/65 (volume ratio)] to give the title compound as a colorless amorphous compound (278 mg, 51%).
Reaction SMILES: [NH:1]([C:3]1[N:8]([CH2:9][C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[C:7](=[O:15])[N:6]([CH2:16][CH2:17][CH3:18])[C:5](=[O:19])[CH:4]=1)[NH2:2].[CH3:20][N:21]=[C:22]=S.CO>CN(C=O)C>[CH3:20][NH:21][C:22]1[C:4]2[C:5](=[O:19])[N:6]([CH2:16][CH2:17][CH3:18])[C:7](=[O:15])[N:8]([CH2:9][C:10]3[S:11][CH:12]=[CH:13][CH:14]=3)[C:3]=2[NH:1][N:2]=1
Reactant: CCCn1c(=O)cc(NN)n(Cc2cccs2)c1=O
Reactant: CN=C=S
Solvent: CN(C)C=O
Solvent: CO
Product: CCCn1c(=O)c2c(NC)n[nH]c2n(Cc2cccs2)c1=O
Reaction time: 12 h

Procedure:
A solution of 6-hydrazino-3-propyl-1-(2-thienylmethyl)uracil (1.8 g, 6.4 mM) and methyl isothiocyanate (1.36 ml, 20 mM) in DMF (30 ml) was stirred at 60° C. for 5 hours and then at 110° C. for 12 hours. To the solution was added methanol (10 ml) and the mixture was cooled to give crystals. Recrystallization from DMF/methanol afforded colorless crystals (0.9 g, 44%), m.p. >300° C.
Reaction SMILES: NN.[CH3:3][O:4][C:5](=[O:17])[CH2:6][N:7]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH3:16])[CH:10]=1)[NH2:8].[O-:18][C:19]#[N:20].[Na+].FC(F)(F)C(O)=O>C1(C)C=CC=CC=1.CCOCC>[NH2:20][C:19]([NH:8][N:7]([CH2:6][C:5]([O:4][CH3:3])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH3:16])[CH:10]=1)=[O:18]
Reactant: N#C[O-]
Reactant: CCc1cccc(N(N)CC(=O)OC)c1
Agent: NN
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOCC
Solvent: O=C(O)C(F)(F)F
Product: CCc1cccc(N(CC(=O)OC)NC(N)=O)c1
Reaction time: 3 h
Yield: 49 %

Procedure:
To the hydrazine (Intermediate 39; 3.75 g; 0.018 mol) and sodium cyanate (3.54 g; 0.054 mol) in toluene (30 ml) was added, dropwise, trifluoroacetic acid (5.82 g; 3.93 ml; 0.051 mol). This mixture was stirred for 3 h. and was then quenched with sodium bicarbonate and extracted into ethyl acetate. The organic extract was washed with sodium bicarbonate, water and brine and then dried (Na2SO4). Filtration and evaporation gave a cream solid which, on trituration with ether, afforded the title compound as a white solid (2.21 g; 49%), m.p. 128°-130° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6].[C:13](Cl)(=O)[CH:14]([CH3:16])[CH3:15].C(N(CC)CC)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(OCC)(=O)C.C1(C)C(C)=CC=CC=1>[CH:14]([C:16]1[O:12][C:11]2[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=2[N:1]=1)([CH3:15])[CH3:13]
Reactant: CC(C)C(=O)Cl
Reactant: COC(=O)c1ccc(O)c(N)c1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1C
Product: COC(=O)c1ccc2oc(C(C)C)nc2c1
Temperature: 25 °C
Yield: 104 %

Procedure:
A solution of methyl 3-amino-4-hydroxybenzoate (5.00 g, 29.9 mmol), isobutyryl chloride (3.51 g, 32.9 mmol), triethylamine (3.33 g, 32.9 mmol), pyridinium p-toluenesulfonate (2.5 g, 10 mmol) and xylene (100 mL) was heated to reflux overnight and then cooled to room temperature. The reaction was diluted with ethyl acetate (100 mL) and washed with water (2×50 mL), dried with magnesium sulfate, filtered and concentrated to give the title compound (6.82 g, quantitative yield) as a brown oil. Also prepared by this method were:
Reaction SMILES: [CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]#[N:23])=[CH:16][C:15]4=[O:24])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:3][CH2:2]1.[NH4+:25].[Cl-:26]>CO.C[O-].[Na+]>[ClH:26].[CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22](=[NH:25])[NH2:23])=[CH:16][C:15]4=[O:24])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:2][CH2:3]1
Reactant: Cn1c(C2CC2)nc2ccc(-n3ccc(OCC#N)cc3=O)cc21
Reactant: [NH4+]
Reactant: [Cl-]
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: Cl
Product: Cn1c(C2CC2)nc2ccc(-n3ccc(OCC(=N)N)cc3=O)cc21
Temperature: 25 °C
Reaction time: 4 h
Yield: 105.1 %

Procedure:
To a solution of ((1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-2-oxo-1,2-dihydropyridin-4-yl)oxy)acetonitrile (300 mg) in MeOH (4 ml) was added sodium methoxide (2.5 mg), and the mixture was stirred at room temperature for 4 h. NH4Cl (52.6 mg) was added to the mixture, and the mixture was stirred at room temperature overnight. The solvent was evaporated, and the residual solid was washed with IPA-IPE to give the title compound (368 mg) as a light brown solid.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7][C:6]=2[N:12]=1.C(N(CC)CC)C.[H][H]>[Pd].CO>[N:12]1[C:6]2[CH2:7][CH2:8][NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: [H][H]
Reactant: Clc1ccc2c(n1)CCNCC2
Agent: [Pd]
Solvent: CO
Solvent: CCN(CC)CC
Product: c1cnc2c(c1)CCNCC2

Procedure:
Under a hydrogen atmosphere 0.125 g (0.49 mmol) 2-chloro-6,7,8,9-tetrahydro-5H-pyri do[2,3-d]azepine, 30 mg palladium on charcoal (10%) and 0.28 mL triethylamine in 4 mL methanol were hydrogenated at RT under 50 psi hydrogen pressure for 6 h. The catalyst was removed and the filtrate was concentrated to dryness. The residue was used without further purification. Yield: 72 mg (99% of theory). ESI-MS: m/z=149 (M+H)+; Rt(HPLC): 0.52 min (Method J).
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)[N:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.C1C=[N:27][C:26]2[N:29]([OH:32])N=N[C:25]=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.ONC(=N)C.CN([CH:59]=[O:60])C>>[OH:32]/[N:29]=[C:26](\[NH:27][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([O:60][CH3:59])[CH:15]=[CH:16][C:8]=1[NH:7][C:5]1[N:4]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:3]=[C:2]([CH3:1])[CH:6]=1)/[CH3:25]
Reactant: Cc1cc(Nc2ccccc2C(=O)O)n(-c2ccccc2)n1
Reactant: CN(C)C=O
Reactant: On1nnc2cccnc21
Agent: CC(=N)NO
Agent: CCN=C=NCCCN(C)C
Solvent: CCN(CC)CC
Product: COc1ccc(Nc2cc(C)nn2-c2ccccc2)c(C(=O)N/C(C)=N\O)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a mixture of 2-[(3-methyl-1-phenyl-1H-pyrazol-5-yl)amino]benzoic acid (400 mg, 1.04 mmol) (prepared by the sequence of Buchwald-type coupling and hydrolysis, similar to Examples 108 and 109), HOAT (186 mg, 1.39 mmol), and EDCI (263 mg, 1.39 mmol) in DMF (7 mL) at −20° C. was added triethylamine (0.45 mL, 3.25 mmol). After stirring at that temperature for 15 min, N-hydroxy-acetamidine (305 mg, 2.78 mmol) was added, and the temperature was slowly raised to rt. Stirring was continued for 16 h, the solvent was evaporated in vacuo and the residue was partitioned between water and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed successively with 5% citric acid, saturated aqueous Na2CO3 solution and brine, dried (MgSO4), filtered, and concentrated to give 147 mg of a crude solid. This solid was used in the next step with no further purification. ES-MS m/z 380.1 (MH+); HPLC RT (min) 2.53.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[C@@H:4]([CH2:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[NH:5]C(OC(C)(C)C)=O.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][O:2][C:3](=[O:22])[C@@H:4]([CH2:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[NH2:5]
Reactant: COC(=O)[C@@H](COCc1ccccc1)NC(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Solvent: ClCCl
Product: COC(=O)[C@H](N)COCc1ccccc1
Reaction time: 4 h

Procedure:
To a solution of tert-butyloxycarbonyl-O-benzyl-D-serine methyl ester (BF8-EZ0-275) (5.0 g, 16 mmol) stirring in dichloromethane (40 mL) and anisole (1 ml) at 0° C. was added trifluoroacetic acid (10 mL). After 4 h at room temperature, a saturated aqueous solution of sodium bicarbonate was added and the resulting mixture extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sufate, and concentrated. The crude product was used in the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:27]([CH3:29])[CH3:28])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([NH:16][CH:17]([CH:21]([OH:26])[C:22]([F:25])([F:24])[F:23])[CH:18]([CH3:20])[CH3:19])=[O:15])=[O:8])=[O:4].[Mn]([O-])(=O)(=O)=O.[K+]>CO>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:27]([CH3:29])[CH3:28])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([NH:16][CH:17]([C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])[CH:18]([CH3:20])[CH3:19])=[O:15])=[O:8])=[O:4]
Reactant: COC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)NC(C(C)C)C(O)C(F)(F)F)C(C)C
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CO
Product: COC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)NC(C(=O)C(F)(F)F)C(C)C)C(C)C
Temperature: 10 °C
Reaction time: 1 h
Yield: 75 %

Procedure:
Using a similar oxidation procedure to that described in Example 2, but using (S)-1-[(S)-2-(methoxycarbonylamino)-3-methylbutyryl]-N-[2-methyl-1-(2,2,2-trifluoro-1-hydroxyethyl)propyl]-pyrrolidine-2-carboxamide and adding the potassium permanganate solution at 5-10° C. and then stirring at 10° C. for one hour prior to treatment with methanol, there was obtained (after work-up by extraction into tert-butyl methyl ether, followed by washing with brine and concentration in vacuo) (S)-1-[(S)-2-(methoxycarbonylamino)-3-methylbutyryl]-N-[2-methyl-1-(2,2,2-trifluoroacetyl)propyl]-pyrrolidine-2-carboxamide as a gum (in 75% yield); SSS:SSR ratio of 53:47; hydrate:ketone 1:1; 1H NMR similar to that of the product of Example 1. [Using a similar procedure, but adding the potassium permanganate solution at ambient temperature instead of 5-10° C., the product was obtained in a ratio of SSS:SSR of 47:53.]
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C@H:8]([OH:10])[CH3:9])[CH:7]=1.N[N:14]1[CH:19]=[C:18](Br)[CH:17]=[C:16]([Cl:21])[NH:15]1.C[Si](C)(C)[N-:24][Si](C)(C)C.[Na+]>O1CCCC1>[Cl:21][C:16]1[N:15]=[N:14][C:19]([NH2:24])=[C:18]([O:10][C@@H:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:11][CH3:12])[CH3:9])[CH:17]=1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: NN1C=C(Br)C=C(Cl)N1
Reactant: COc1ccc(F)cc1[C@@H](C)O
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(F)cc1[C@@H](C)Oc1cc(Cl)nnc1N
Temperature: 66 °C
Yield: 54 %

Procedure:
To a solution of (R)-1-(5-fluoro-2-methoxy-phenyl)-ethanol (4.78 g, 28 mmol, 1.5 eq.) in tetrahydrofuran (40 mL) was added 2-amino-4-bromo-6-chloro-pyridazine (3.9 g, 18.7 mmol) followed by a solution of sodium hexamethyldisilazide (1M in tetrahydrofuran, 28.1 mL, 1.5 eq.). This mixture was then heated to 66° C. for 18 hr before cooling and evaporating under reduced pressure. The residue was purified by chromatography on silica gel (150 g) eluting with a gradient of ethyl acetate in heptane (10:90 to 50:50) to give the title compound as a yellow solid (3.0 g, 54%).
Reaction SMILES: Cl[C:2]1C=CC=C(C(OO)=O)[CH:3]=1.C(S[C:15]1[C:16]([C:21]([N:23]([CH3:35])[C:24]2[CH:29]=[CH:28][C:27]([S:30][C:31]([F:34])([F:33])[F:32])=[CH:26][N:25]=2)=[O:22])=[N:17][CH:18]=[CH:19][CH:20]=1)C.C(=O)(O)[O-].[Na+].[S:41]([O-:45])([O-])(=[O:43])=S.[Na+].[Na+]>C(Cl)(Cl)Cl>[CH2:2]([S:41]([C:15]1[C:16]([C:21]([N:23]([CH3:35])[C:24]2[CH:29]=[CH:28][C:27]([S:30][C:31]([F:34])([F:33])[F:32])=[CH:26][N:25]=2)=[O:22])=[N:17][CH:18]=[CH:19][CH:20]=1)(=[O:45])=[O:43])[CH3:3]
Reactant: O=S([O-])([O-])=S
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCSc1cccnc1C(=O)N(C)c1ccc(SC(F)(F)F)cn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CCS(=O)(=O)c1cccnc1C(=O)N(C)c1ccc(SC(F)(F)F)cn1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
0.37 g of m-chloroperbenzoic acid (purity of 68%) was added to a mixture of 0.23 g of 3-ethylsulfanyl-N-methyl-N-(5-trifluoromethylsulfanylpyridin-2-yl)picolinamide (Compound of Present Invention 32) and 5 mL of chloroform under ice cooling, and the mixture was stirred at 0° C. for 2 hours. A saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium thiosulfate solution were poured to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure, and the resulting residue was applied to a silica gel column chromatography to obtain 0.20 g of 3-ethylsulfonyl-N-methyl-N-(5-trifluoromethylsulfanylpyridin-2-yl)picolinamide (hereinafter, referred to as Compound of Present Invention 33).
Reaction SMILES: [O:1]=[C:2]1[CH2:8][O:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[O:4][CH2:3]1.[CH:13]#[N:14].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1>[OH:1][C:2]1([C:13]#[N:14])[CH2:3][O:4][C:5]2[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=2[O:7][CH2:8]1
Reactant: C#N
Reactant: O=C1COc2ccccc2OC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Product: N#CC1(O)COc2ccccc2OC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 4.92 g. (30 millimoles) of 3-oxo-3,4-dihydro-2H-1,5-benzodioxepin in 100 mls. of benzene is added dropwise a solution of 30 millimoles of anhydrous hydrogen cyanide in 50 ml. of benzene. The reaction mixture is stirred overnight at ambient temperature, basified with 10% sodium carbonate solution and the organic layer separated. The benzene solution is washed once with water and dried successively over anhydrous magnesium sulfate and calcium sulfate. Evaporation of the solvent under reduced pressure at 40° C. yields the crude cyanohydrin which upon purification and mixed melting point determination gives no depression with an authentic sample of 3-hydroxy-3-cyano-3,4-dihydro-2H-1,5-benzodioxepin.
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:15][SiH:16]([CH:18]([SiH:23]([Cl:25])[Cl:24])[Si:19]([Cl:22])([Cl:21])[Cl:20])[Cl:17]>C1C=CC=CC=1>[Cl:17][Si:16]1([Cl:15])[CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:8]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[Si:23]([Cl:24])([Cl:25])[CH:18]1[Si:19]([Cl:22])([Cl:20])[Cl:21]
Reactant: C(#Cc1ccccc1)c1ccccc1
Reactant: Cl[SiH](Cl)C([SiH](Cl)Cl)[Si](Cl)(Cl)Cl
Solvent: c1ccccc1
Product: Cl[Si](Cl)(Cl)C1[Si](Cl)(Cl)C(c2ccccc2)C(c2ccccc2)[Si]1(Cl)Cl
Reaction time: 18 h
Yield: 13.8 %

Procedure:
Hydrosilation of diphenylacetylene with bis(dichlorosilyl)trichlorosilylmethane in the presence of Pt(C2H4)(PPh3)2. Into the same apparatus as described in Example 1 were added 0.99 g of bis(dichlorosilyl)trichlorosilylmethane, 0.102 g of Pt(C2H4)(PPh3)2, and 25 ml of dried benzene to form a mixture. To this mixture at reflux was added 0.52 g of diphenylacetylene in 10 ml of benzene over a 30 minute period. The resulting mixture was stirred for an additional 18 hours and then the solvent remove at atmospheric pressure. The residue was vacuum distilled at 67 Pa to yield a mixture comprising 0.61 g of 1,1,3,3-tetrachloro-2-trichlorosilyl-4,5-diphenyl-1,3-disilacyclopentane (TCD-GC area 13.8%).
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:15]([NH:22][CH2:23][CH2:24][C:25]1[CH:40]=[CH:39][C:28]([O:29][C:30]2[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=[CH:32][N:31]=2)=[CH:27][CH:26]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH:41](=O)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(O)(=O)C.[OH-].[Na+]>ClCCCl>[CH2:15]([N:22]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[CH2:23][CH2:24][C:25]1[CH:40]=[CH:39][C:28]([O:29][C:30]2[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=[CH:32][N:31]=2)=[CH:27][CH:26]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: O=Cc1ccccc1
Reactant: NC(=O)c1ccc(Oc2ccc(CCNCc3ccccc3)cc2)nc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: NC(=O)c1ccc(Oc2ccc(CCN(Cc3ccccc3)Cc3ccccc3)cc2)nc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 64.9 %

Procedure:
Add sodium triacetoxyborohydride (0.2600 g, 1.227 mmol) to a stirred solution of 6-[4-(2-benzylamino-ethyl)-phenoxy]-nicotinamide (0.3058 g, 0.8802 mmol), benzaldehyde (0.092 mL, 0.905 mmol), glacial acetic acid (0.052 mL, 0.908 mmol) and 1,2-dichloroethane (8 mL). Stir for 18 h at room temperature under nitrogen. Pour the reaction into 1N sodium hydroxide (50 mL) and extract with diethyl ether (3×50 mL). Wash the diethyl ether extracts with brine, dry over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 75% ethyl acetate/hexanes to yield 0.2501 g (65%) of 6-[4-(2-dibenzylamino-ethyl)-phenoxy]-nicotinamide: HPLC (30/70 to 90/10 ACN/(0.1% TFA in water) Zorbax SB-Phenyl Column 4.6 mm×5 cm×5 micron: Retention time: 8.14 minutes, Purity: 99.7%; mass spectrum (ion spray): m/z=438.0 (M+1).
Reaction SMILES: [S:1](=[C:4]1[CH:9]=[CH:8][O:7][C:6]([C:10]([O:12][C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19]C)=[O:18])=[C:15]([O:23][CH3:24])[CH:14]=2)=[O:11])=[CH:5]1)(=[O:3])=[O:2].O.O[Li].O>C1COCC1>[S:1](=[C:4]1[CH:9]=[CH:8][O:7][C:6]([C:10]([O:12][C:13]2[CH:22]=[CH:21][C:16]([C:17]([OH:19])=[O:18])=[C:15]([O:23][CH3:24])[CH:14]=2)=[O:11])=[CH:5]1)(=[O:2])=[O:3]
Reactant: COC(=O)c1ccc(OC(=O)c2cc(=S(=O)=O)cco2)cc1OC
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(OC(=O)c2cc(=S(=O)=O)cco2)ccc1C(=O)O
Temperature: 45 °C

Procedure:
To a stirred solution of methyl 4-[4-sulfonylpyranoyloxy]-2-methoxybenzoate (470 mg, 1.5 mmol)in THF:H2O (18 mL: 2 mL) was added LiOH.H2O (128 mg, 3 mmol). The reaction was heated to 45° C. over 12 h and then cooled to ambient temperature. The solvent was removed under reduced pressure. The crude solid passed through a plug of silca gel packed in 80:20 hexanes:EtOAc and eluted with same. The solvent was removed under reduced pressure to afford 4-[4-sulfonylpyranoyloxy]-2-methoxybenzoic acid as a white solid.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C:9]1[S:10][CH:11]=[C:12]([C:14]([N:16]2[CH2:21][C:20]3([CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[O:19][CH2:18][CH2:17]2)=[O:15])[N:13]=1.[Si:27]([O:34][CH2:35][CH2:36][C:37]1[S:41][C:40]([CH:42]=O)=[CH:39][CH:38]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1C(=O)CCC1>[Si:27]([O:34][CH2:35][CH2:36][C:37]1[S:41][C:40]([CH2:42][N:24]2[CH2:25][CH2:26][C:20]3([O:19][CH2:18][CH2:17][N:16]([C:14]([C:12]4[N:13]=[C:9]([CH3:8])[S:10][CH:11]=4)=[O:15])[CH2:21]3)[CH2:22][CH2:23]2)=[CH:39][CH:38]=1)([C:30]([CH3:31])([CH3:33])[CH3:32])([CH3:29])[CH3:28]
Reactant: Cc1nc(C(=O)N2CCOC3(CCNCC3)C2)cs1
Reactant: CC(C)(C)[Si](C)(C)OCCc1ccc(C=O)s1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: CC(=O)O
Solvent: CN1CCCC1=O
Product: Cc1nc(C(=O)N2CCOC3(CCN(Cc4ccc(CCO[Si](C)(C)C(C)(C)C)s4)CC3)C2)cs1

Procedure:
A solution of (2-methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.25 g) and 5-(2-(tert-butyldimethylsilyloxy)ethyl)thiophene-2-carbaldehyde (example 14, step a) (0.171 g) in NMP (5 mL) with acetic acid (0.036 mL) was treated with sodium triacetoxyborohydride (0.201 g) and the resultant mixture stirred at 20° C. for 18 hours. The mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution, the organic layer was washed with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 0.3 g.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][CH:24]=4)[NH:21][C:20]([CH2:25][C:26]([O:28]CC)=[O:27])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.O[Li].O.O.ClCCl>C1COCC1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][CH:24]=4)[NH:21][C:20]([CH2:25][C:26]([OH:28])=[O:27])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CCOC(=O)Cc1cc2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2[nH]1
Agent: [Li]O
Solvent: O
Solvent: C1CCOC1
Solvent: ClCCl
Product: O=C(O)Cc1cc2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2[nH]1

Procedure:
To a solution of ethyl 2-(5-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-1H-indol-2-yl)acetate (0.010 g, 0.025 mmol) in THF (0.3 mL) were added LiOH.H2O (0.002 g, 0.05 mmol) and water (0.15 mL) were added. The mixture was stirred at room temperature for 2 h. dichloromethane (3 mL) was added to the reaction mixture and the organic layer was washed with 1 N HCl (2×1.5 mL) and water (2×1.5 mL). The organic layer was dried over Na2SO4 and filtered. The filtrate was evaporated under reduced pressure to give 2-(5-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-1H-indol-2-yl)-acetic acid. 1H NMR (400 MHz; DMSO-d6) δ 12.53 (s, 1H), 10.90 (s, 1H), 8.42 (s, 1H), 7.57 (s, 1H), 7.17 (d, J=8.6 Hz, 1H), 7.05-6.90 (m, 4H), 6.17 (s, 1H), 6.02 (s, 2H), 3.69 (s, 2H), 1.41-1.39 (m, 2H), 1.04-1.02 (m, 2H).