Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]1([C:18]([OH:20])=[O:19])[CH2:16][CH2:15][C:14](=[O:17])[O:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[N+:23]([C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1)([O-:25])=[O:24].C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][C:12]1([C:18]([O:20][CH2:30][C:29]2[CH:32]=[CH:33][C:26]([N+:23]([O-:25])=[O:24])=[CH:27][CH:28]=2)=[O:19])[CH2:16][CH2:15][C:14](=[O:17])[O:13]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCC(NC(=O)OCc2ccccc2)(C(=O)O)O1
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C1CCC(NC(=O)OCc2ccccc2)(C(=O)OCc2ccc([N+](=O)[O-])cc2)O1
Yield: 55.3 %

Procedure:
To a solution of 838 mg of 2-benzyloxycarbonylamino-5-oxo-2-tetrahydrofurancarboxylic acid in 5 ml of dimethylformamide was added 120 mg of sodium hydride (60% oil) while stirring under ice-cooling. To the mixture was then added 648 mg of 4-nitrobenzyl bromide, followed by stirring at room temperature for 2.5 hours. To the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate, which was subjected to extraction with ethyl acetate. The organic layer was washed with a saturated aqueous saline solution and then dried (MgSO4), followed by distilling off the solvent. The residue was subjected to a silica gel column chromatography, eluting with hexane-ethyl acetate (1:1). Fractions containing the end product were combined and concentrated under reduced pressure to give 687 mg of 4-nitrobenzyl 2-benzyloxycarbonylamino-5-oxo-2-tetrahydrofurancarboxylate as colorless crystals, m.p. 127°-127.5° C.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].C(N(CC)CC)C.[Cl-].ClC1N(C)CC[NH+]1C.[CH3:28][O:29][C:30]1[C:31](=[O:54])[C:32]([CH3:53])=[C:33]([CH2:39][C:40]2[CH:41]=[CH:42][C:43]([O:49][C:50](=[O:52])[CH3:51])=[C:44]([CH:48]=2)[C:45](O)=[O:46])[C:34](=[O:38])[C:35]=1[O:36][CH3:37]>C(Cl)Cl>[CH3:28][O:29][C:30]1[C:31](=[O:54])[C:32]([CH3:53])=[C:33]([CH2:39][C:40]2[CH:41]=[CH:42][C:43]([O:49][C:50](=[O:52])[CH3:51])=[C:44]([CH:48]=2)[C:45]([NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=2)=[O:46])[C:34](=[O:38])[C:35]=1[O:36][CH3:37]
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)O)c2)=C(C)C1=O
Reactant: Nc1cccc(C(F)(F)F)c1
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)Nc3cccc(C(F)(F)F)c3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 45.4 %

Procedure:
3-Trifluoromethylaniline (0.483 g, 3.000 mmol), triethylamine (0.304 g, 3.000 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (0.507 g, 3.000 mmol) were added to a methylene chloride solution (100 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.374 g, 1.000 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=10:1) and then recrystallized from ether to obtain the titled compound (0.235 g, 0.454 mmol, 45%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:21]([NH:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([F:32])[CH:26]=3)=[O:22])=[C:7]([CH:18]([CH3:20])[CH3:19])[N:8]2[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:4][CH:3]=1.Br[CH2:34][CH2:35][CH2:36][CH2:37]Br.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[F:32][C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][C:28]=1[F:31])[CH2:24][NH:23][C:21]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([N:1]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:3][CH:4]=2)[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[C:7]=1[CH:18]([CH3:20])[CH3:19])=[O:22]
Reactant: CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(N)cc2n1Cc1ccccn1
Reactant: BrCCCCBr
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Product: CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(N3CCCC3)cc2n1Cc1ccccn1
Temperature: 110 °C

Procedure:
To a solution of 6-amino-N-(3,4-difluorobenzyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide (Compound 182, 64 mg, 0.15 mmol) in toluene (2 ml) was added 1,4-dibromobutane (19 μl, 0.16 mmol) and i-Pr2NEt (77 μl, 0.44 mmol). The reaction was heated at 110° C. for 16 h, and was purified directly by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound.
Reaction SMILES: [CH2:1]([N:8]([CH2:21][C:22]1[CH:42]=[CH:41][C:25]([O:26][C:27]2[CH:28]=[C:29]([CH:38]=[CH:39][CH:40]=2)[O:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([OH:37])=O)=[CH:24][CH:23]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[C:10]=1[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C([O:46][C:47](=[O:51])[CH2:48][CH2:49][NH2:50])C>>[CH2:1]([N:8]([CH2:21][C:22]1[CH:42]=[CH:41][C:25]([O:26][C:27]2[CH:28]=[C:29]([CH:38]=[CH:39][CH:40]=2)[O:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([NH:50][CH2:49][CH2:48][C:47]([OH:51])=[O:46])=[O:37])=[CH:24][CH:23]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[C:10]=1[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(NS(C)(=O)=O)cccc1N(Cc1ccccc1)Cc1ccc(Oc2cccc(OCCCCC(=O)O)c2)cc1
Reactant: CCOC(=O)CCN
Agent: Cl
Product: Cc1c(NS(C)(=O)=O)cccc1N(Cc1ccccc1)Cc1ccc(Oc2cccc(OCCCCC(=O)NCCC(=O)O)c2)cc1

Procedure:
The product from Example 117B and β-alanine ethyl ester hydrochloride were processed as described in Example 104B to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.97 (s, 1 H), 7.86 (t, 1 H), 7.23 (m, 8 H), 6.88-7.08 (m, 5 H), 6.67 (m, 1 H), 6.48 (m, 2 H), 4.06 (s, 2 H), 4.03 (s, 2 H), 3.91 (t, 2 H), 3.35 (br.s, 1 H), 3.22 (dd, 2 H), 2.91 (s, 3 H), 2.40 (s, 3 H), 2.35 (t, 2 H), 2.09 (t, 2 H), 1.50-1.74 (m, 4 H); MS (APCI) m/z 658 (M−H−).
Reaction SMILES: [C:1]([C:3]1[S:7][C:6]([O:8][C:9]2[CH:10]=[C:11]([CH3:25])[C:12]3[CH:16]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[O:15][B:14]([OH:23])[C:13]=3[CH:24]=2)=[N:5][CH:4]=1)#[N:2].Cl.[NH2:27][OH:28].C(N(CC)CC)C>CO>[OH:23][B:14]1[C:13]2[CH:24]=[C:9]([O:8][C:6]3[S:7][C:3]([C:1](=[NH:2])[NH:27][OH:28])=[CH:4][N:5]=3)[CH:10]=[C:11]([CH3:25])[C:12]=2[CH:16]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[O:15]1
Reactant: NO
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3ncc(C#N)s3)cc(C)c21
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CO
Product: CCOC(=O)CC1OB(O)c2cc(Oc3ncc(C(=N)NO)s3)cc(C)c21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of ethyl 2-(6-(5-cyanothiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate (2.5 g, 7 mmol, 1 eq.) and hydroxylamine hydrochloride (1.21 g, 17.4 mmol, 2.5 eq.) in methanol was added triethylamine (3.41 ml, 24.5 mmol, 3.5 eq.). After stirring at room temperature overnight, the reaction mixture was evaporated under reduced pressure. The residue was dissolved in EtOAc and then washed with water. The organic layers were collected, dried with Na2SO4 and evaporated to give the crude product as a yellow solid. The crude was used in subsequent steps without further purification.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:30])[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([C:20]34[CH2:29][CH:24]5[CH2:25][CH:26]([CH2:28][CH:22]([CH2:23]5)[CH2:21]3)[CH2:27]4)[CH:13]=2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+].O>CO>[OH:3][CH:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:30])[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([C:20]34[CH2:29][CH:24]5[CH2:25][CH:26]([CH2:28][CH:22]([CH2:23]5)[CH2:21]3)[CH2:27]4)[CH:13]=2)=[CH:6][CH:5]=1)[CH3:2]
Reactant: COc1ccc(C(=O)Nc2ccc(C(C)=O)cc2)cc1C12CC3CC(CC(C3)C1)C2
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ccc(C(=O)Nc2ccc(C(C)O)cc2)cc1C12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 48 h
Yield: 66 %

Procedure:
The amide obtained in Example 23, above, (0.9 g, 2 mmoles) is dissolved in methanol (25ml) and treated with 0.12 g (3 mmoles) of sodium borohydride. The mixture is stirred at ambient temperature for 2 days, poured into water and extracted with ether. The extracts are dried on magnesium sulfate, then the solvent is evaporated. The resulting residue is recrystallized in ethyl acetate to give N[4-[1-hydroxyethyl)phenyl]-3-(1-adamantyl)-4-methoxy benzamide (0.5 g, 66% yield) having a melting point of 207°-209° C.
Reaction SMILES: [C@@H:1]1([O:12][C:13]2[C:18]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)=[C:17]([CH3:28])[CH:16]=[C:15]([CH3:29])[N:14]=2)[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@H:2]1[OH:3].Cl[C:31](OC)=[O:32].C(O)(=O)C[C:37](CC(O)=O)(C(O)=O)[OH:38]>CC1C=C(C)C=C(C)N=1.ClCCl>[CH3:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][C:18]2[C:13]([O:12][C@@H:1]3[O:9][C@H:8]([C:10](=[C:31]=[O:32])[O:11][O:38][CH3:37])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@H:2]3[OH:3])=[N:14][C:15]([CH3:29])=[CH:16][C:17]=2[CH3:28])=[CH:21][CH:22]=1
Reactant: COc1ccc(Cc2c(C)cc(C)nc2O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Reactant: COC(=O)Cl
Solvent: Cc1cc(C)nc(C)c1
Solvent: ClCCl
Product: COOC(=C=O)[C@H]1O[C@@H](Oc2nc(C)cc(C)c2Cc2ccc(OC)cc2)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 7 h

Procedure:
To a solution of 2-(β-D-glucopyranosyloxy)-3-(4-methoxy-benzyl)-4,6-dimethylpyridine (0.32 g) in 2,4,6-trimethyl-pyridine (3.8 mL) was added a solution of methyl chloroformate (0.18 mL) in dichloromethane (0.4 mL) at −40° C. The temperature was raised to room temperature, and the mixture was stirred for 7 hours. To the reaction mixture was added 10% aqueous citric acid solution (12 mL), and the mixture was extracted with ethyl acetate. After the organic layer was washed with 10% aqueous citric acid solution and dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate) to give 3-(4-methoxybenzyl)-2-(6-O-methoxy-carbonyl-β-D-glucopyranosyloxy)-4,6-dimethylpyridine (0.27 g).
Reaction SMILES: CO.[C:3](=[O:6])([O-:5])[O-:4].[Na+].[Na+].[OH:9][CH2:10][CH:11]([CH2:13][OH:14])[OH:12]>>[C:3](=[O:4])([OH:6])[OH:5].[OH:9][CH2:10][CH:11]([CH2:13][OH:14])[OH:12]
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: OCC(O)CO
Product: O=C(O)O

Procedure:
In one embodiment, the DMC/methanol mixture is reacted with glycerine in the presence of a base catalyst such as sodium carbonate in a reactor connected to a distillation column. The reactor and column do not have to be physically connected, but it is more efficient to do so. The reaction is allowed to proceed to equilibrium. Some of the DMC reacts with the glycerine to form glycerine carbonate. However, some of the DMC and glycerine remain unreacted. The lighter components, including DMC and methanol, are removed by distillation, flash distillation, stripping, or any known suitable method. The bottom product mixture includes the desired glycerine carbonate, unreacted glycerine, and some methanol and DMC. For example, the glycerine carbonate may be present in the bottom product mixture in an amount between 10% and 65% by weight or between 20% and 35% by weight. After stripping, the bottom product mixture includes 10% or less by weight of DMC or methanol; preferably, 5% or less by weight of DMC or methanol; and more preferably, 2% or less by weight of DMC or methanol.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.[H-].[Na+].[N+]([C:15]1[CH:16]=[C:17]([CH3:22])[N+:18]([O-:21])=[CH:19][CH:20]=1)([O-])=O>CN1CCCC1=O.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:15]2[CH:20]=[CH:19][N+:18]([O-:21])=[C:17]([CH3:22])[CH:16]=2)=[C:4]([F:9])[CH:3]=1
Reactant: Cc1cc([N+](=O)[O-])cc[n+]1[O-]
Reactant: Oc1ccc(Br)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: Cc1cc(Oc2ccc(Br)cc2F)cc[n+]1[O-]
Temperature: 180 °C
Reaction time: 0.33 h

Procedure:
To a solution of 4-bromo-2-fluorophenol (3.44 ml, 31.41 mmol) in N-methylpyrrolidone (20 ml) at r.t., was added sodium hydride (1.34 g, 56 mmol, 60% in mineral oil) portionwise. After stirring for 20 min, 4-nitro-2-picoline N-oxide (5.6 g, 36.12 mmol) was added. The reaction mixture was heated at 180° C. for 60 min. under microwave irradiation. After cooling to r.t. the mixture was diluted with EtOAc (250 ml), washed with water (250 ml) and then extracted with additional EtOAc (2×150 ml). The combined organic extracts were dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 2% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D25 (4.36 g, 47%).
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].[N+:12]([O-])([O-:14])=[O:13].[Na+].S(=O)(=O)(O)O.N([O-])=O.[Na+]>C(Cl)Cl>[N+:12]([C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:10])([F:11])[F:1])[C:4]=1[OH:9])([O-:14])=[O:13]
Reactant: Oc1ccccc1C(F)(F)F
Reactant: O=[N+]([O-])[O-]
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClCCl
Product: O=[N+]([O-])c1cccc(C(F)(F)F)c1O
Reaction time: 24 h
Yield: 48 %

Procedure:
2-trifluoromethylphenol (3.00 g, 18.5 mmol) was dissolved in methylene chloride(40 mL) followed by the addition of sodium nitrate (1.73 g, 20.4 mmol). The addition of sulfuric acid (23 mL/3M) was then made, followed by addition of a catalytic amount of sodium nitrite. The mixture was allowed to stir. After 24 hours, the reaction mixture was diluted with methylene chloride and extracted with water. The organic layer was dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (4% MeOH/CH2Cl2) gave the desired product(1.84 g, 47%). 1H NMR (CD3COCD3): δ 8.35 (d, 1H), 7.95 (d, 1H), 7.13 (t, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[C:18]([N+:19]([O-:21])=[O:20])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH:5]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:7]=1.C(N(CC)CC)C.[CH:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][C:30]=1[C:39](Cl)=[O:40].C(=O)(O)[O-].[Na+]>O1CCOCC1.C(OCC)(=O)C>[CH3:11][O:10][C:8]([C:6]1[CH:5]=[C:4]([NH:12][C:13]2[C:18]([N+:19]([O-:21])=[O:20])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH:3]=[C:2]([NH:1][C:39]([C:30]2[CH:31]=[CH:32][C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH:29]=2)=[O:40])[CH:7]=1)=[O:9]
Reactant: COC(=O)c1cc(N)cc(Nc2ncccc2[N+](=O)[O-])c1
Reactant: O=C(Cl)c1ccc2ccccc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(NC(=O)c2ccc3ccccc3c2)cc(Nc2ncccc2[N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 86.5 %

Procedure:
To a mixture of 2-(3-amino-5-methoxycarbonylphenylamino)-3-nitropyridine (550 mg) and triethylamine (0.3 ml) in 1,4-dioxane (10 ml) was added 2-naphthoyl chloride (0.40 g). The mixture was stirred at room temperature for 15 minutes, then poured into a mixture of ethyl acetate and aqueous sodium bicarbonate. The organic phase containing orange solid was washed with water twice and the solid was collected to give 2-[3-methoxycarbonyl-5-(2-naphthoylamino)phenylamino]-3-nitropyridine (730 mg).
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][C:7]1([CH3:17])[C@H:12]2[CH2:13][C@@H:8]1[CH2:9][CH2:10][C@@H:11]2CC#N.[CH2:18]([OH:20])[CH3:19].[OH:21]S(O)(=O)=O>C(O)C.O>[CH3:6][C:7]1([CH3:17])[C@H:12]2[CH2:13][C@@H:8]1[CH2:9][CH2:10][C@@H:11]2[CH2:19][C:18]([OH:21])=[O:20]
Reactant: O=S(=O)(O)O
Reactant: CCO
Reactant: CC1(C)[C@H]2CC[C@H](CC#N)[C@@H]1C2
Solvent: O
Product: CC1(C)[C@H]2CC[C@H](CC(=O)O)[C@@H]1C2
Temperature: 40 °C

Procedure:
Concentrated sulfuric acid (33 mL) was added drop wise to ethanol (120 mL) at 0° C. A solution of Example 21B (7.20 g, 44.1 mmol) in ethanol (20 mL) was added to the ethanol-H2SO4 mixture. The mixture was heated at reflux for 24 hours. TLC showed a 1/1 mixture of ethyl ester and acid. The mixture was diluted with water. Ethanol was evaporated under reduced pressure and the mixture was extracted with ether. The organic extracts were dried with magnesium sulfate, filtered, and concentrated. The residue was dissolved in tetrahydrofuran (50 mL). To the mixture was added a solution of 25% NaOH (10 mL). The reaction was heated at 40° C. for 12 hours. The mixture was cooled at room temperature, tetrahydrofuran was evaporated, the mixture was diluted with brine and washed with ether (2×25 mL). The aqueous phase was acidified to pH 2 with 5 N HCl and extracted with ether (3×75 mL). The organic extracts were dried over magnesium sulfate, filtered, and concentrated to give the title compound.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([NH2:7])=[N:4][CH:3]=1.[C:8]1([CH:14]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15](Cl)=[O:16])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH3:1][C:2]1[O:6][C:5]([NH:7][C:15](=[O:16])[CH:14]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:4][CH:3]=1
Reactant: Cc1cnc(N)o1
Reactant: O=C(Cl)C(c1ccccc1)c1ccccc1
Product: Cc1cnc(NC(=O)C(c2ccccc2)c2ccccc2)o1

Procedure:
The title compound, off-white solid, m.p. 166-168° C. and MS: m/e=292.2 (M+) was prepared in accordance with the general method of example 44a from 5-methyl-oxazol-2-ylamine and 2,2-diphenyl acetic acid chloride.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:16])[CH:3]=1.[Si]([C:21]([F:24])([F:23])[F:22])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:13]=2[CH:14]([OH:15])[C:21]([F:24])([F:23])[F:22])=[C:4]([F:16])[CH:3]=1
Reactant: O=Cc1cnccc1-c1ccc(Cl)cc1F
Reactant: C[Si](C)(C)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: ClCCl
Product: OC(c1cnccc1-c1ccc(Cl)cc1F)C(F)(F)F
Reaction time: 1.5 h
Yield: 75 %

Procedure:
A stirred solution of 4-(4-chloro-2-fluorophenyl)nicotinaldehyde (1.8 g, 7.64 mmol) (prepared as described in Example 5, Part B) and TMS-CF3 (0.521 mL, 3.52 mmol) in dichloromethane (20 mL) was stirred at 0° C. for 20 min. TBAF (1.0 M in THF) (0.4 mL, 1.528 mmol) was added dropwise slowly and the solution stirred for 90 min. Water was added and the solution extracted with dichloromethane (2×25 mL). The combined organic layers were washed with brine, dried over sodium sulphate, concentrated and purified by Prep. TLC using 25% ethyl acetate in hexane to give 1-(4-(4-chloro-2-fluorophenyl)pyridin-3-yl)-2,2,2-trifluoroethanol (1 g, 2.64 mmol, 35% yield) as a yellow oil. LCMS (ESI) m/e 306.0 [(M+H)+, calcd for C13H9ClF4NO 306.02]; LC/MS retention time (Method C): tR=2.05 min.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([C:13]3[CH:14]=[CH:15][CH:16]=[C:17]([S:19]([NH:22][Si](C(C)(C)C)(C)C)(=[O:21])=[O:20])[CH:18]=3)=[O:12])=[CH:8][CH:9]=2)[N:4]([Si](C(C)(C)C)(C)C)[CH:3]=1.C(Cl)Cl.CO.[OH-].[NH4+:43]>>[CH3:8][C:7]1[CH:6]=[C:5]([C:2]2[C:10]3[C:5](=[CH:6][C:7]([C:11]([C:13]4[CH:18]=[C:17]([S:19]([NH2:22])(=[O:21])=[O:20])[CH:16]=[CH:15][CH:14]=4)=[O:12])=[CH:8][CH:9]=3)[NH:4][CH:3]=2)[CH:10]=[CH:9][N:43]=1
Reactant: CC(C)(C)[Si](C)(C)NS(=O)(=O)c1cccc(C(=O)c2ccc3c(Br)cn([Si](C)(C)C(C)(C)C)c3c2)c1
Reactant: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: Cc1cc(-c2c[nH]c3cc(C(=O)c4cccc(S(N)(=O)=O)c4)ccc23)ccn1

Procedure:
3-[3-(2-Methyl-pyridin-4-yl)-1H-indole-6-carbonyl]-benzenesulfonamide is prepared from 0.25 g of 5-[3-bromo-1-(tert-butyl-dimethyl-silyl)-1H-indole-6-carbonyl]-N-(tert-butyl-dimethyl-silyl)-benzenesulfonamide according to the procedure described in Example 6 (microwave irradiation at 150° C. for 5 min). MS (m/z): 390 (M−1); Rf 0.19 (90:10:1 methylene chloride/methanol/ammonium hydroxide)
Reaction SMILES: CC1C(C)=C(C)[SiH](C)[SiH-](C)(C)C=1.[Na+].C(OP([CH2:22][C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])(OCC)=O)C.C(=O)=O.C(#N)C.[CH2:39]([CH:41]1[CH:67]=[C:66]([CH3:68])[CH2:65][CH:64]([CH3:69])[CH2:63][CH:62]([O:70][CH3:71])[CH:61]2[O:72][C:57]([OH:76])([CH:58]([CH3:75])[CH2:59][CH:60]2[O:73][CH3:74])[C:56](=[O:77])[C:55](=[O:78])[N:54]2[CH:49]([CH2:50][CH2:51][CH2:52][CH2:53]2)[C:48](=[O:79])[O:47][CH:46]([C:80]([CH3:91])=[CH:81][CH:82]2[CH2:87][CH2:86][C:85](=O)[CH:84]([O:89][CH3:90])[CH2:83]2)[CH:45]([CH3:92])[CH:44]([O:93][Si:94]([C:97]([CH3:100])([CH3:99])[CH3:98])([CH3:96])[CH3:95])[CH2:43][C:42]1=[O:101])[CH3:40]>C1COCC1>[CH2:39]([CH:41]1[CH:67]=[C:66]([CH3:68])[CH2:65][CH:64]([CH3:69])[CH2:63][CH:62]([O:70][CH3:71])[CH:61]2[O:72][C:57]([OH:76])([CH:58]([CH3:75])[CH2:59][CH:60]2[O:73][CH3:74])[C:56](=[O:77])[C:55](=[O:78])[N:54]2[CH:49]([CH2:50][CH2:51][CH2:52][CH2:53]2)[C:48](=[O:79])[O:47][CH:46]([C:80]([CH3:91])=[CH:81][CH:82]2[CH2:87][CH2:86][C:85](=[CH:22][C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[O:24])[CH:84]([O:89][CH3:90])[CH2:83]2)[CH:45]([CH3:92])[CH:44]([O:93][Si:94]([C:97]([CH3:98])([CH3:99])[CH3:100])([CH3:96])[CH3:95])[CH2:43][C:42]1=[O:101])[CH3:40]
Reactant: CCOP(=O)(CC(=O)OCc1ccccc1)OCC
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(=O)C(OC)C3)C(C)C(O[Si](C)(C)C(C)(C)C)CC1=O)C(C)CC2OC
Agent: CC1=C[SiH-](C)(C)[SiH](C)C(C)=C1C
Agent: O=C=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC#N
Product: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(=CC(=O)OCc4ccccc4)C(OC)C3)C(C)C(O[Si](C)(C)C(C)(C)C)CC1=O)C(C)CC2OC
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 63.3 %

Procedure:
A solution of 20 mL of a 1.0 M solution of sodium hexamethyldisilamide in THF was cooled to 0° C. in an ice bath under nitrogen. Then a solution of 5.85 g (20 mmole) of benzyl diethylphosphonoacetate in 10 mL of dry THF was added and the solution was stirred at 0° C. under nitrogen. After 15 min., the solution was cooled to -40° C. (dry ice-acetonitrile bath) under nitrogen, and 4.5 g (5 mmole) of 17-ethyl-1-hydroxy-12-[2'-(4"-oxo-3"-methoxycyclohexyl)-1'-methylvinyl]-14-t-butyl-dimethylsilyloxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (Example 9) in 10 mL of dry tetrahydrofuran was added dropwise over 5 minutes and the solution was stirred at -40° C. under nitrogen. After 3 hr, the reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry THF. Et2O was added and the mixture was partitioned between Et2O and water and the aqueous layer was washed with Et2O. The organic extracts were sequentially washed with saturated KHCO3 solution and brine, then the combined extract was dried over MgSO4, filtered and the filtrate was concentrated in vacuo. The oily residue was purified by flash chromatography (silica gel, 6 cm×20 cm) using ethyl acetate-hexane to afford 3.28 g (63%) of the title compound as a colorless foam; NMR (CDCl3) indicated about a 9:1 mixture of E::Z olefin isomers; MS (FAB) 1042 (M+Li).