Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.Cl.CN(CCO[C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21](Cl)[CH:22]=2)[N:17](C2C=CC(F)=CC=2)[C:16]=1[CH2:32]O)C.CS([Cl:38])(=O)=O.O>ClCCl>[Cl:38][CH2:32][C:16]1[NH:17][C:18]2[C:23]([CH:15]=1)=[CH:22][CH:21]=[CH:20][CH:19]=2
Reactant: CS(=O)(=O)Cl
Reactant: CN(C)CCOc1c(CO)n(-c2ccc(F)cc2)c2ccc(Cl)cc12
Agent: Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: ClCc1cc2ccccc2[nH]1
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
Triethylamine (1 g) was added to a solution of N,N-dimethyl-2-[5-chloro-1-(4-fluorophenyl)-2-hydroxymethyl-3-1H-indolyloxy]ethylamine 9 (3 g) in dichloromethane (100 mL) cooled to -10° C. A solution of methanesulfonylchloride (1.1 g) in dichloromethane (25 mL) was added dropwise at -10° to 0° C. After stirring for 1/2 h at 0° C. ice cooled water was added and the organic phase was subsequently worked up leaving the 2-chloromethylindole derivative as an oil. This oil was used immediately without further purification. To a solution of the oil in dry THF was added LiAlH4 (1 g). After refluxing for 1 h, the mixture was cooled on an ice bath and excess LiAlH4 was hydrolyzed by cautiously adding a mixture of 10% water in THF. Inorganic salts were filtered off and the solvent evaporated in vacuo . The resulting visceous oil was subjected to column chromatography on silica gel (eluted with 4% triethylamine in ethyl acetate) yielding the pure title compound as an oil. Yield: 0.6 g. The oxalic acid salt 10 crystallized from 2-propanol. mp 236°-237° C.; 1H NMR (DMSO-d6) δ 2.15 (s, 3H), 2.85 (s, 6H), 3.40 (t, 2H), 4.35 (t, 2H), 7.00 (d, 1H), 7.05 (dd, 1H), 7.40 (t, 2H), 7.45 (dd, 2H), 7.70 (d, 1H). MS (m/z) 347 (MH+), 274 (6), 223 (36), 222 (20), 72 (100); Anal (C19H20ClFN2O.C2H2O4) C, H, N.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1Cl.[NH2:12][CH2:13][CH2:14][CH2:15][OH:16]>C(O)CCC>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[NH:12][CH2:13][CH2:14][CH2:15][OH:16]
Reactant: NCCCO
Reactant: O=[N+]([O-])c1cccc(Cl)c1Cl
Solvent: CCCCO
Product: O=[N+]([O-])c1cccc(Cl)c1NCCCO

Procedure:
A mixture of 100 parts of 1,2-dichloro-3-nitrobenzene, 95 parts of 3-amino-1-propanol and 200 parts of butanol is stirred and refluxed overnight. The reaction mixture is cooled and evaporated. The residue is taken up in water and the product is extracted with methylbenzene. The extract is washed with water, dried, filtered and evaporated, yielding 115 parts of 3-[(2-chloro-6-nitrophenyl)amino]-1-propanol as a residue.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:14]([O:15][C:16]3[CH:17]=[C:18]([CH:21]=[C:22]([CH3:24])[CH:23]=3)[CH:19]=O)=[C:13]([CH:25]([CH3:27])[CH3:26])[C:12](=[O:28])[NH:11][C:10]2=[O:29])[CH:5]=[C:4]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[N:3]=1.[C:40]([CH2:42]P(=O)(OCC)OCC)#[N:41].CC(C)([O-])C.[K+]>C1COCC1.CC(=O)OCC>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:14]([O:15][C:16]3[CH:17]=[C:18]([CH:19]=[CH:42][C:40]#[N:41])[CH:21]=[C:22]([CH3:24])[CH:23]=3)=[C:13]([CH:25]([CH3:27])[CH3:26])[C:12](=[O:28])[NH:11][C:10]2=[O:29])[CH:5]=[C:4]([NH:30][CH2:31][C:32]2[CH:33]=[CH:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=2)[N:3]=1
Reactant: CCOP(=O)(CC#N)OCC
Reactant: COc1ccc(CNc2cc(Cn3c(Oc4cc(C)cc(C=O)c4)c(C(C)C)c(=O)[nH]c3=O)cc(Cl)n2)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1ccc(CNc2cc(Cn3c(Oc4cc(C)cc(C=CC#N)c4)c(C(C)C)c(=O)[nH]c3=O)cc(Cl)n2)cc1
Reaction time: 1 h
Yield: 69.5 %

Procedure:
To a stirred solution of 3-{3-[2-chloro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy}-5-methyl-benzaldehyde (335 mg, 0.611 mmol) and diethyl cyanomethyl-phosphonate (104 μl, 0.64 mmol) in THF (10 ml) at 0° C. (ice bath) under nitrogen atmosphere, was added potassium t-butoxide (151 mg, 1.34 mmol). After stirring for 1 hr., the mixture was stirred for overnight at room temperature. The mixture was then diluted with EA, washed with aqueous saturated ammonium chloride solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)) to afford 243 mg (70%) of a white foam. 1H NMR (200 MHz, CDCl3) δ 1.10 (6H, d, J=6.8 Hz), 2.32 (3H, s), 2.68 (1H, m), 3.78 (3H, s), 4.30 (2H, d, J=5.2 Hz), 4.68 (2H, s), 5.23 (1H, t, J=5.2 Hz), 5.82 (1H, d, J=16.6 Hz), 6.05 (1H, s), 6.21 (1H, s), 6.62 (2H, s), 6.84-6.90 (2H, m), 6.97 (1H, s), 7.18-7.27 (3H, m), 9.63 (1H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH3:9].[C:10](Cl)(=[O:13])[CH2:11][CH3:12].[Cl-].[Cl-].[Cl-].[Al+3]>>[Cl:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5]([OH:8])=[C:6]([C:10](=[O:13])[CH2:11][CH3:12])[CH:7]=1
Reactant: Cc1cc(O)ccc1Cl
Reactant: CCC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Product: CCC(=O)c1cc(Cl)c(C)cc1O
Temperature: 60 °C
Yield: 60 %

Procedure:
The 4-chloro-3-methyl-phenol (2 g, 10 mmol) and the propionyl chloride (1.8 mL, 20. mmol) were combined and the mixture was heated at 60° C. for 2 hours. The reaction was concentrated in vacuo to remove excess propionyl chloride to give an oil. To this was added aluminum trichloride (2.7 g, 20. mmol) and the mixture was heated at 180° C. for 30 minutes. The reaction mixture was then cooled to room temperature and slowly quenched with 1 N HCl while cooling in an ice bath. The reaction was partitioned between EtOAc and water. The organic layer was washed with 1 N HCl, water, brine, dried over magnesium sulfate and concentrated to give the crude product as a dark oil. The product was purified by chromatography on silica gel eluting with hexane:EtOAc gradient to give 1-(5-chloro-2-hydroxy-4-methylphenyl)propan-1-one as a solid (1.5 g, 60%). LCMS calculated for C10H12ClO2 (M+H)+: m/z=199.0. found: 198.9.
Reaction SMILES: [H][H].[Al+3].[Cl-].[Cl-].[Cl-].[Cl:7][C:8]1[CH:16]=[CH:15][C:11]([C:12](Cl)=[O:13])=[CH:10][CH:9]=1.[CH3:17][N:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[CH2:23][C:24]#[N:25]>>[Cl:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([C:22]2[N:18]([CH3:17])[C:19]([CH2:23][C:24]#[N:25])=[CH:20][CH:21]=2)=[O:13])=[CH:10][CH:9]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: [H][H]
Reactant: Cn1cccc1CC#N
Agent: [Al+3]
Agent: [Cl-]
Product: Cn1c(CC#N)ccc1C(=O)c1ccc(Cl)cc1
Yield: 21 %

Procedure:
The uncatalyzed aroylation process of this invention surprisingly affords better yields of the product, 4-R1 -1-loweralkyl-5-aroylpyrrole-2-acetic acid ester or nitrile. Moreover, when R1 is hydrogen, the usual alpha to beta ratio of product in acylation reactions, that is, the distribution of α-aroylated and β-aroylated isomers, is very greatly shifted in favor of the α-substituted product. For example, in the AlCl3 catalyzed Friedel Crafts reaction of p-chlorobenzoyl chloride with 1-methylpyrrole-2-acetonitrile, a 21% yield of the α-product, 5-(p-chlorobenzoyl)-1-methylpyrrole-2-acetonitrile, is obtained and the ratio of this α-isomer to the corresponding β-isomer, 4-(p-chlorobenzoyl)-1-methylpyrrole-2-acetonitrile, is about 2.5:1; and in the similarly catalyzed reaction of p-toluoyl chloride with 1-methylpyrrole-2-acetonitrile, a 25% yield of the α-product, 5-(p-toluoyl)-1-methylpyrrole-2-acetonitrile, is obtained with an alpha to beta isomer ratio of 3.7:1 [see Carson et al., J. Med. Chem., 14, 646 (1971)]. In contrast, the uncatalyzed reaction of p-chlorobenzoyl chloride with 1-methylpyrrole-2-acetonitrile in refluxing xylene for about 24 hours affords 46% of the corresponding α-product with an α/β ratio of about 440:1; and the uncatalyzed reaction of p-toluoyl chloride with 1-methylpyrrole-2-acetonitrile in refluxing o-dichlorobenzene for about 4 hours affords 55% of the corresponding α-product with an α/β ratio of about 180:1.
Reaction SMILES: CO[C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)=[N:14][O:15][CH:16]=2)=[N:6][CH:5]=1.[CH:25]1([NH2:28])[CH2:27][CH2:26]1>>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([C:13]2[C:12]([CH2:11][O:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([NH:28][CH:25]4[CH2:27][CH2:26]4)=[O:24])=[CH:5][N:6]=3)=[CH:16][O:15][N:14]=2)=[CH:22][CH:21]=1
Reactant: NC1CC1
Reactant: COC(=O)c1ccc(OCc2conc2-c2ccc(Cl)cc2)nc1
Product: O=C(NC1CC1)c1ccc(OCc2conc2-c2ccc(Cl)cc2)nc1
Yield: 46 %

Procedure:
As described for example 342 g, 6-[3-(4-chloro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (200 mg, 0.58 mmol) was converted, using cyclopropylamine instead of 2,2,2-trifluoroethylamine, to the title compound (100 mg, 46%) which was obtained as a white solid. MS: m/e=370.0 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([CH2:11][CH2:12][CH3:13])([CH2:7][C:8](O)=[O:9])[CH2:3][C:4](O)=[O:5].[NH4+:14].[OH-]>>[CH3:1][C:2]1([CH2:11][CH2:12][CH3:13])[CH2:7][C:8](=[O:9])[NH:14][C:4](=[O:5])[CH2:3]1
Reactant: [NH4+]
Reactant: CCCC(C)(CC(=O)O)CC(=O)O
Agent: [OH-]
Product: CCCC1(C)CC(=O)NC(=O)C1
Reaction time: 4 h
Yield: 80 %

Procedure:
A 10 g (0.06 mole) quantity of the anhydride prepared in Example 1 was added in small portions to 120 mL conc. NH4OH. After the addition was completed, the mixture was heated to a gentle reflux and stirred for 4 hr. Upon cooling the reaction mixture, a yellow oil precipitated which solidified to a glass. Crystallization of the glass from isopropyl alcohol gave 8 g (80%) of crude product, m.p. 110°-120° C. (literature m.p. 115°-116°, Cf: N. S. Benica and C. O. Wilson, J. Am. Pharm. Assoc., 39, page 451-454 (1950)).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[C:7]([C:9]1[C:14]([C:15](OC)=[O:16])=[CH:13][CH:12]=[CH:11][N:10]=1)=O)([O-:3])=[O:2].O.[NH2:23][NH2:24].C(OCC)(=O)C>C(O)C>[N+:1]([C:4]1[CH:5]=[C:6]([C:7]2[C:9]3[N:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:15](=[O:16])[NH:24][N:23]=2)[CH:19]=[CH:20][CH:21]=1)([O-:3])=[O:2]
Reactant: COC(=O)c1cccnc1C(=O)c1cccc([N+](=O)[O-])c1
Reactant: NN
Solvent: CCO
Solvent: O
Solvent: CCOC(C)=O
Product: O=c1[nH]nc(-c2cccc([N+](=O)[O-])c2)c2ncccc12
Yield: 108.1 %

Procedure:
To a solution of 2-(3-nitrobenzoyl)-3-methoxycarbonylpyridine (0.58 g, 2 mmoles) dissolved in ethanol (50 ml), was added hydrazine monohydrate (0.25 ml, 5.1 mmoles). The mixture was refluxed for 4 hours, cooled and ethyl acetate (50 ml) was added. The solid material was collected and dried, yielding 0.58 g of 8-(3-nitrophenyl)-pyrido[2,3-d]pyridazin-5-one, mp 302° C.
Reaction SMILES: O1CCCC1.C(NC(C)C)(C)C.[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][N:15]=1.[I:21]I>C([Li])CCC.O>[Cl:13][C:14]1[C:19]([Cl:20])=[C:18]([I:21])[CH:17]=[CH:16][N:15]=1
Reactant: II
Reactant: Clc1cccnc1Cl
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: Clc1nccc(I)c1Cl
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 70588.8 %

Procedure:
With cooling with ice, 2.66 M n-butyllithium (100 mL, 0.266 mmol) was added to a tetrahydrofuran (400 mL) solution of diisopropylamine (11.9 mL, 84.2 mmol), cooled to −70° C., and stirred for 0.5 hours. A tetrahydrofuran (170 mL) solution of 2,3-dichloropyridine (35 g, 0.24 mmol) was dropwise added to the solution, over 25 minutes, and then stirred at −70° C. for 1 hour. A tetrahydrofuran (170 mL) solution of iodine (75 g, 0.30 mmol) was added to the reaction mixture, and warmed up to room temperature with stirring. Water was added to the reaction mixture, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. Ethyl acetate and hexane were added to the residue, the precipitated matter was taken out through filtration and dried to obtain the entitled compound (46.4 g, 72%) as a pale yellow solid.
Reaction SMILES: [OH-].[C:2]([C:5]1[CH:36]=[CH:35][C:8]([O:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:31]=[CH:30][C:17]3[C:18](=[O:29])[CH2:19][C:20]([CH2:23][CH2:24][C:25]([O:27]C)=[O:26])([CH3:22])[O:21][C:16]=3[C:15]=2[CH2:32][CH2:33][CH3:34])=[C:7]([CH2:37][CH2:38][CH3:39])[C:6]=1[OH:40])(=[O:4])[CH3:3]>O.O1CCCC1.CO>[C:2]([C:5]1[CH:36]=[CH:35][C:8]([O:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:31]=[CH:30][C:17]3[C:18](=[O:29])[CH2:19][C:20]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])([CH3:22])[O:21][C:16]=3[C:15]=2[CH2:32][CH2:33][CH3:34])=[C:7]([CH2:37][CH2:38][CH3:39])[C:6]=1[OH:40])(=[O:4])[CH3:3]
Reactant: CCCc1c(OCCCOc2ccc3c(c2CCC)OC(C)(CCC(=O)OC)CC3=O)ccc(C(C)=O)c1O
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CCCc1c(OCCCOc2ccc3c(c2CCC)OC(C)(CCC(=O)O)CC3=O)ccc(C(C)=O)c1O
Temperature: 25 °C
Reaction time: 3 h
Yield: 89.1 %

Procedure:
A solution of 0.5 g (19.5 mmole) of liythium hydroxide in 10 ml of water was added to a solution of 2.2 g (3.9 mmole) of the title compound of Example 6 in 25 ml of tetrahydrofuran and 20 ml of methanol. After the reaction mixture was stirred for 3 hours at room temperature, the solvent was evaporated and water was added to the residue. After extracting with a small amount of diethyl ether, the aqueous layer was acidified with dilute hydrochloric acid and allowed to stand in the cold overnight. The solid was filtered, washed with water and recrystallized from ethyl acetate/hexane to yield 1.83 g of the title compound, mp. 80°-83°. Structure assignment was confirmed by nmr and infrared spectra and by elemental analysis.
Reaction SMILES: [N:1]([CH:4]1[CH2:23][N:8]2[C:9]3[C:14]([C:15]([CH2:16][C:17]([O:19]CCC)=[O:18])=[C:7]2[CH2:6][CH2:5]1)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[N+:2]=[N-:3].[C:24]([C:26]1[CH:31]=[CH:30][C:29]([C:32]([OH:35])([CH3:34])[CH3:33])=[CH:28][CH:27]=1)#[CH:25]>>[OH:35][C:32]([C:29]1[CH:28]=[CH:27][C:26]([C:24]2[N:3]=[N:2][N:1]([CH:4]3[CH2:23][N:8]4[C:9]5[C:14]([C:15]([CH2:16][C:17]([OH:19])=[O:18])=[C:7]4[CH2:6][CH2:5]3)=[CH:13][CH:12]=[CH:11][CH:10]=5)[CH:25]=2)=[CH:31][CH:30]=1)([CH3:34])[CH3:33]
Reactant: CCCOC(=O)Cc1c2n(c3ccccc13)CC(N=[N+]=[N-])CC2
Reactant: C#Cc1ccc(C(C)(C)O)cc1
Product: CC(C)(O)c1ccc(-c2cn(C3CCc4c(CC(=O)O)c5ccccc5n4C3)nn2)cc1

Procedure:
The title compound was prepared using procedures described in EXAMPLE 1 from propyl (7-azido-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate and 2-(4-ethynylphenyl)propan-2-ol. MS (+ESI) m/z: 431.2.
Reaction SMILES: [O:1]([CH2:19][C:20]1([CH2:28][N:29]2[CH:33]=[C:32]([CH2:34][OH:35])[N:31]=[C:30]2[N+:36]([O-:38])=[O:37])[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22][CH2:21]1)[Si:2]([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.[CH3:48][O:49][CH2:50]Cl.C(=O)(O)[O-].[Na+]>ClCCl>[O:1]([CH2:19][C:20]1([CH2:28][N:29]2[CH:33]=[C:32]([CH2:34][O:35][CH2:48][O:49][CH3:50])[N:31]=[C:30]2[N+:36]([O-:38])=[O:37])[CH2:25][O:24][C:23]([CH3:26])([CH3:27])[O:22][CH2:21]1)[Si:2]([C:15]([CH3:16])([CH3:18])[CH3:17])([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: COCCl
Reactant: CC1(C)OCC(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)(Cn2cc(CO)nc2[N+](=O)[O-])CO1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COCOCc1cn(CC2(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)COC(C)(C)OC2)c([N+](=O)[O-])n1
Temperature: 0 °C
Reaction time: 26 h
Yield: 78.9 %

Procedure:
101 mg (0.19 mmol equivalents) of 5-(t-butyldiphenylsiloxymethyl)-2,2-dimethyl-5-[(4-hydroxymethyl-2-nitro-1H-imidazol-1-yl)methyl]-1,3-dioxane was dissolved in 2.0 mL of dichloromethane and cooled to about 0° C. in an ice bath. 125 μL (0.72 mmol equivalents) of N,N-diisopropylethylamine and 41 μL (0.51 mmol equivalents) of methoxymethyl chloride were added thereto, and the mixture was stirred for 26 hours while increasing the temperature to room temperature (25° C.). After completion of the reaction, a saturated aqueous solution of sodium bicarbonate was added dropwise, and the mixture was extracted three times with ethyl acetate. The combined ethyl acetate layers were washed with water and brine, then dried with anhydrous magnesium sulfate, and subsequently concentrated under vacuum. The obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=2/1) to give 86 mg (0.15 mmol equivalents) of 5-(t-butyldiphenylsiloxymethyl)-2,2-dimethyl-5-[(4-methoxymethoxymethyl-2-nitro-1H-imidazol-1-yl)methyl]-1,3-dioxane.
Reaction SMILES: [F:1][C:2]([F:39])([S:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=O)[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10].[F:40][C:41]([F:54])([F:53])[S:42]([O:45]S(C(F)(F)F)(=O)=O)(=[O:44])=[O:43].C(OCC)C>ClC(Cl)(F)C(Cl)(F)F>[F:40][C:41]([F:54])([F:53])[S:42]([O-:45])(=[O:44])=[O:43].[F:1][C:2]([F:39])([S+:25]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]1=2)[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10]
Reactant: O=S(c1ccccc1-c1ccccc1)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: FC(F)(Cl)C(F)(Cl)Cl
Solvent: CCOCC
Product: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)[s+]1c2ccccc2c2ccccc21
Product: O=S(=O)([O-])C(F)(F)F
Temperature: 25 °C
Reaction time: 72 h
Yield: 90.4 %

Procedure:
To a solution of 1.24 g (2 mmol) of 2-(perfluorooctylsulfinyl)biphenyl in 10 ml of 1,1,2-trichloro -1,2,2-trifluoroethane was added 0.336 ml (2 mmol) of trifluoromethanesulfonic anhydride, and the mixture was stirred at room temperature for 3 days. Then, 0.112 ml (0.67 mmol) of trifluoromethanesulfonic anhydride was added to the reaction mixture and the mixture was stirred for additional 2 days. After diethyl ether was added to the reaction mixture, a white precipitate was collected by filtration to give 1.36 g (91%) of S-(perfluorooctyl)dibenzothiophenium trifluoromethanesulfonate. The properties of the product are shown in Table 1.
Reaction SMILES: [C:1](=[O:3])=[O:2].[CH3:4][C:5](C)=O.[F:8][C:9]([F:13])=[C:10](F)F.[H-].[Na+].C(O)C=C.C([Li])CCC>C1COCC1.O>[F:8][C:9]([F:13])([CH2:10][CH:4]=[CH2:5])[C:1]([OH:3])=[O:2]
Reactant: O=C=O
Reactant: FC(F)=C(F)F
Reactant: CC(C)=O
Agent: [H-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C=CCO
Solvent: O
Solvent: C1CCOC1
Product: C=CCC(F)(F)C(=O)O
Temperature: -50 °C
Reaction time: 3 h

Procedure:
A 250 ml, three-necked flask equipped with a magnetic stir bar, a low-temperature thermometer, a condenser filled with dry ice/acetone, and a balloon is charged with dry THF (100 mL). The flask is cooled to approximately −50° C. and tetrafluoroethylene is passed through a tube of silica and then through a needle into the THF until saturation is reached (as judged by inflation of the balloon). The flask is allowed to warm to −5 to −10° C. which causes the balloon to inflate slightly (most of the gas will be trapped by the condenser). To a separate 50 ml. flask is added NaH (100 mg, 4.2 mmol, 80% suspension in oil), and the oil is removed by repeated washing with dry THF under argon. A solution of previously distilled allyl alcohol (3.0 g 52 mmol) in dry THF (2 ml) is slowly added by syringe with stirring and the mixture is allowed to stir for an additional 10 min. This solution is then transferred dropwise by syringe to the three-necked flask with stirring at −5 to −10° C. After approximately 3 hr, the reaction is checked by GC (60° C.) of a small aliquot and, if needed, additional tetrafluoroethylene is bubbled into the solution for about 5 min. The product elutes just after the allyl alcohol. Further additions of tetrafluoroethylene are usually required. The addition reaction usually requires 6 hr. The reaction is then placed under argon, cooled to −60° C. and n-butyllithium (one equivalent in hexane) is added dropwise over 2 hr. from an addition funnel while the temperature is kept constant at −60° C. The mixture is cooled to −78° C., water (2 ml) is added, the cooling bath is removed and the solution is stirred overnight. The solution is basified with aqueous NaOH and the solvent removed in vacuo. The residue is acidified with 1N HCl and extracted three times with ether. The organic layers are combined and extracted with saturated NaHCO3. The aqueous extract is acidified to pH 1 with HCl and extracted three times with ether. The presence of the difluoro acid is confirmed by NMR of a small aliquot.
Reaction SMILES: [Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[C:18]([CH3:28])=[N:19][N:20]4[CH:25]=[CH:24][C:23](C=O)=[CH:22][C:21]=34)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)=[CH:4][CH:3]=1.[C:31](O)(=O)C.C(Cl)Cl.[CH3:38][O:39][C:40]1[CH:47]=[C:46]([O:48][CH3:49])[CH:45]=[CH:44][C:41]=1[CH2:42][NH2:43].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[C:18]([CH3:28])=[N:19][N:20]4[CH:25]=[CH:24][C:23]([CH2:31][NH:43][CH2:42][C:41]5[CH:44]=[CH:45][C:46]([O:48][CH3:49])=[CH:47][C:40]=5[O:39][CH3:38])=[CH:22][C:21]=34)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)=[CH:4][CH:3]=1
Reactant: COc1ccc(CN)c(OC)c1
Reactant: CC(=O)O
Reactant: Cc1nn2ccc(C=O)cc2c1-c1nc(Cc2ccc(Cl)cc2)c(-c2nnc[nH]2)s1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COc1ccc(CNCc2ccn3nc(C)c(-c4nc(Cc5ccc(Cl)cc5)c(-c5nnc[nH]5)s4)c3c2)c(OC)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 62.3 %

Procedure:
To a suspension of 3-[4-(4-chlorobenzyl)-5-(4H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-2-methylpyrazolo[1,5-a]pyridine-5-carbaldehyde (0.300 g, 0.690 mmol) in acetic acid (0.20 mL, 3.5 mmol) and dry methylene chloride (10 mL, 200 mmol) was added 2,4-dimethoxybenzylamine (0.207 mL, 1.38 mmol), followed by additional of sodium triacetoxyborohydride (0.363 g, 1.71 mmol). The mixture was stirred at rt. for 16 hours. The mixture was basified with NaHCO3 solution to ˜pH 8 then extracted with DCM. The DCM solution was washed with water. The crude product was purified by column chromatography (SiO2, elution with 0-100% MeOH in DCM) to afford a solid product (0.252 g, yield 62%). LCMS: (FA) ES+ 586, 588; ES− 584, 586. 1H NMR (400 MHz, CDCl3 and d4-methanol) δ: 8.23-8.25 (d, J=7.03 Hz, 1H), 8.18 (s, 1H), 8.01 (s, 1H), 7.28-7.30 (d, J=8.53 Hz, 2H), 7.09-7.11 (d, J=8.53 Hz, 2H), 7.01-7.03 (d, J=8.28 Hz, 1H), 6.78-6.80 (d, J=7.03 Hz, 1H), 6.33-6.37 (m, 2H), 4.53 (s, 2H), 3.65 (s, 2H), 3.64 (s, 6H), 3.61 (s, 2H), 2.61 (s, 3H).