Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.O1CCCC1.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:42]=[CH:43][CH:44]=1)[O:26][C:27]1[N:32]=[C:31]2[S:33][C:34]([NH:36][C:37]([CH:39]3[CH2:41][CH2:40]3)=[O:38])=[N:35][C:30]2=[CH:29][CH:28]=1>CN(C)C=O.CN(C)C(=O)C>[CH:39]1([C:37]([NH:36][C:34]2[S:33][C:31]3[C:30]([N:35]=2)=[CH:29][CH:28]=[C:27]([O:26][C:25]2[CH:24]=[C:23]([NH:22][C:8]([C:3]4[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=4)=[O:10])[CH:44]=[CH:43][CH:42]=2)[N:32]=3)=[O:38])[CH2:40][CH2:41]1
Reactant: Cc1cccnc1C(=O)O
Reactant: Nc1cccc(Oc2ccc3nc(NC(=O)C4CC4)sc3n2)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: CC(=O)N(C)C
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: Cc1cccnc1C(=O)Nc1cccc(Oc2ccc3nc(NC(=O)C4CC4)sc3n2)c1
Yield: 76.8 %

Procedure:
In the same manner as in Example 18-4 and using 3-methylpyridine-2-carboxylic acid (132 mg, 0.965 mmol), tetrahydrofuran (8 mL), oxalyl chloride (169 μL, 1.93 mmol), N-[5-(3-aminophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (210 mg, 0.643 mmol), N,N-dimethylformamide (1 drop) and N,N-dimethylacetamide (5 mL) as starting materials, the title compound (220 mg, 77%) was obtained as a white solid.
Reaction SMILES: [CH2:1]1[CH:9]2[N:4]([CH2:5][CH2:6][C:7]3[NH:12][C:11]4[N:13]=[CH:14][CH:15]=[CH:16][C:10]=4[C:8]=32)[CH2:3][CH2:2]1.[OH-].[K+].[F:19][C:20]([F:30])([F:29])[C:21]1[CH:26]=[CH:25][C:24]([CH:27]=[CH2:28])=[CH:23][N:22]=1>CN1C(=O)CCC1.O>[F:30][C:20]([F:19])([F:29])[C:21]1[N:22]=[CH:23][C:24]([CH2:27][CH2:28][N:12]2[C:7]3[CH2:6][CH2:5][N:4]4[CH:9]([C:8]=3[C:10]3[CH:16]=[CH:15][CH:14]=[N:13][C:11]2=3)[CH2:1][CH2:2][CH2:3]4)=[CH:25][CH:26]=1
Reactant: c1cnc2[nH]c3c(c2c1)C1CCCN1CC3
Reactant: C=Cc1ccc(C(F)(F)F)nc1
Agent: [K+]
Agent: [OH-]
Solvent: CN1CCCC1=O
Solvent: O
Product: FC(F)(F)c1ccc(CCn2c3c(c4cccnc42)C2CCCN2CC3)cn1
Reaction time: 24 h

Procedure:
A solution of 2,3,5,6,7,11c-hexahydro-1H-pyrido[3′,2′:4,5]pyrrolo[2,3-g]indolizine (120 mg, 0.565 mmol) and powdered KOH (221.5 mg, 3.955 mmol) in NMP (2 mL) was stirred at RT for 10 min. 2-(Trifluoromethyl)-5-vinylpyridine (195.5 mg, 1.13 mmol) was added into the reaction mixture and stiffing continued for 24 h at RT. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified by silica gel flash chromatography to yield 7-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-2,3,5,6,7,11c-hexahydro-1H-pyrido[3′,2′:4,5]pyrrolo[2,3-g]indolizine;
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH2:4].[CH2:10]1[C:23]2[C:14](=[N:15][C:16]3[C:17](=O)[CH2:18][CH2:19][CH2:20][C:21]=3[CH:22]=2)[C:13](=O)[CH2:12][CH2:11]1>>[CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[N:4]=[C:13]1[C:14]2[C:23](=[CH:22][C:21]3[CH2:20][CH2:19][CH2:18][C:17](=[N:4][C:3]4[C:5]([CH3:9])=[CH:6][CH:7]=[CH:8][C:2]=4[CH3:1])[C:16]=3[N:15]=2)[CH2:10][CH2:11][CH2:12]1
Reactant: Cc1cccc(C)c1N
Reactant: O=C1CCCc2cc3c(nc21)C(=O)CCC3
Product: Cc1cccc(C)c1N=C1CCCc2cc3c(nc21)C(=Nc1c(C)cccc1C)CCC3

Procedure:
was synthesized by methods similar to those in Examples 3 and 4: 2,6-dimethylaniline was condensed with 2,3,7,8-tetrahydro-1H,6H-acridine-4,5-dione to yield 4,5-bis[2,6-dimethylphenylimino]-1,2,3,4,5,6,7,8-octahydroacridine (3). The complexation of (3) with FeCl2.4H2O was carried out with azeotropic removal of methanol in benzene. The structure of final complex was proved by X-ray analysis.
Reaction SMILES: [CH3:1][N:2]=[C:3]=[O:4].[N+:5]([C:8]1[CH:9]=[C:10]([NH:15][OH:16])[CH:11]=[CH:12][C:13]=1[CH3:14])([O-:7])=[O:6].C([O:19][CH2:20]C)C>>[N+:5]([C:8]1[CH:9]=[C:10]([N:15]2[C:3](=[O:4])[N:2]([CH3:1])[C:20](=[O:19])[O:16]2)[CH:11]=[CH:12][C:13]=1[CH3:14])([O-:7])=[O:6]
Reactant: CCOCC
Reactant: CN=C=O
Reactant: Cc1ccc(NO)cc1[N+](=O)[O-]
Product: Cc1ccc(-n2oc(=O)n(C)c2=O)cc1[N+](=O)[O-]

Procedure:
A solution of methyl isocyanate (4.1 g; 4.6 ml.) in diethyl ether (20 ml.) was added with stirring to a solution of N-(3-nitro-4-methylphenyl)-hydroxylamine (12.0 g.) in ether (70 ml.) at room temperature over a period of about 10 minutes. The yellow precipitate 1-methyl-3-(3'-nitro-4'-methylphenyl)-3-hydroxyurea which formed was filtered and air dried.
Reaction SMILES: [S:1]1[C:5]([S-:6])=[CH:4][N:3]=[N:2]1.[Na+].Cl[CH2:9][C:10]#[N:11]>ClCCl.CN(C)C=O>[S:1]1[C:5]([S:6][CH2:9][C:10]#[N:11])=[CH:4][N:3]=[N:2]1
Reactant: N#CCCl
Reactant: [S-]c1cnns1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: N#CCSc1cnns1
Reaction time: 8 h

Procedure:
To a stirred solution of sodium 1,2,3-thiadiazol-5-thiolate (15 g) in dichloromethane (150 ml) and dimethylformamide (20 ml) was added chloroacetonitrile (4.76 ml) at room temperature. After stirring overnight, the precipitate was filtered off and the filtrate was poured into the mixture of water (30 ml) and dichloromethane (300 ml). The organic layer was separated, washed with brine and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (450 ml) eluting with ethyl acetate to give (1,2,3-thiadiazol-5-yl)thioacetonitrile (10 g).
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH:14]=[O:15].[OH-:16].[Na+]>[N+]([O-])([O-])=O.[Ag+]>[CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[CH:4]=[CH:3][C:2]=1[C:14]([OH:16])=[O:15]
Reactant: O=Cc1ccc2oc3ccccc3c2c1
Reactant: [OH-]
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Product: O=C(O)c1ccc2oc3ccccc3c2c1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To dibenzofuran-2-carboxaldehyde (17) (200 mg, 1.02 mmol) was added solid NaOH (49 mg, 1.22 mmol) then 10% NaOH solution (1.8 mL). Silver nitrate (173 mg, 1.02 mmol) was then added, the reaction mixture heated to 60° C. for 1.5 hours and then stirred overnight at ambient temperature. The reaction mixture was then filtered and washed with water. The filtrate was acidified to pH 2 using concentrated HCl and the precipitated product filtered and dried to give the title compound as an off-white solid. Yield: 83 mg, 38%; LC-MS tr 1.31 min; HPLC Purity: 100%; MS (ES+) m/z not detectable (M+H)
Reaction SMILES: [CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]([OH:14])=O)=[CH:11][C:6]=2[N:5]=[C:4]1[NH:15][C:16]1[S:17][C:18]2[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:19]=2[N:20]=1)[CH3:2].[CH2:29]([O:31][CH2:32][CH2:33][NH2:34])[CH3:30].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:29]([O:31][CH2:32][CH2:33][NH:34][C:12]([C:10]1[CH:9]=[CH:8][C:7]2[N:3]([CH2:1][CH3:2])[C:4]([NH:15][C:16]3[S:17][C:18]4[CH:24]=[C:23]([C:25]([F:26])([F:28])[F:27])[CH:22]=[CH:21][C:19]=4[N:20]=3)=[N:5][C:6]=2[CH:11]=1)=[O:14])[CH3:30]
Reactant: CCOCCN
Reactant: CCn1c(Nc2nc3ccc(C(F)(F)F)cc3s2)nc2cc(C(=O)O)ccc21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOCCNC(=O)c1ccc2c(c1)nc(Nc1nc3ccc(C(F)(F)F)cc3s1)n2CC
Yield: 37.4 %

Procedure:
1-Ethyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide (66.0 mg) was prepared by following General Procedure F starting from 1-ethyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (150.0 mg), 2-ethoxy-ethylamine (45.0 mg), HBTU (200.0 mg) and DIEA (0.2 mL) in DMF (1.0 mL). LCMS: m/z 479.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH3:14][O:15][C:16]1[N:21]=[CH:20][C:19]([C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][CH2:27][NH:28][CH:29]3[CH3:32])=[CH:24][CH:23]=2)=[CH:18][CH:17]=1>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:28]3[CH2:27][CH2:26][C:25]4[C:30](=[CH:31][C:22]([C:19]5[CH:20]=[N:21][C:16]([O:15][CH3:14])=[CH:17][CH:18]=5)=[CH:23][CH:24]=4)[CH:29]3[CH3:32])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: COc1ccc(-c2ccc3c(c2)C(C)NCC3)cn1
Reactant: O=C(O)c1cc2ncc(Cl)cn2n1
Product: COc1ccc(-c2ccc3c(c2)C(C)N(C(=O)c2cc4ncc(Cl)cn4n2)CC3)cn1

Procedure:
In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 7-(6-Methoxy-pyridin-3-yl)-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: [Cl-].[CH3:2][S:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]1[O:17][N:16]=[C:15]([C:18]2[N:19]=[C:20]([CH:23]3[CH2:28][CH2:27][NH2+:26][CH2:25][CH2:24]3)[S:21][CH:22]=2)[CH2:14]1)(=[O:5])=[O:4].[C:29]([O:32][CH2:33][C:34](Cl)=[O:35])(=[O:31])[CH3:30].C(N(CC)CC)C.O>ClCCl>[C:29]([O:32][CH2:33][C:34]([N:26]1[CH2:27][CH2:28][CH:23]([C:20]2[S:21][CH:22]=[C:18]([C:15]3[CH2:14][CH:13]([C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=4[O:6][S:3]([CH3:2])(=[O:4])=[O:5])[O:17][N:16]=3)[N:19]=2)[CH2:24][CH2:25]1)=[O:35])(=[O:31])[CH3:30]
Reactant: CC(=O)OCC(=O)Cl
Reactant: CS(=O)(=O)Oc1ccccc1C1CC(c2csc(C3CC[NH2+]CC3)n2)=NO1
Agent: [Cl-]
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(=O)OCC(=O)N1CCC(c2nc(C3=NOC(c4ccccc4OS(C)(=O)=O)C3)cs2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 29.7 %

Procedure:
To 4-[4-(5-{2-[(methylsulphonyl)oxy]phenyl}-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidinium chloride (500 mg) in dichloromethane (6 ml) under argon were added 2-chloro-2-oxoethyl acetate (154 mg) and triethylamine (342 mg). The reaction mixture was stirred at room temperature for 18 hours. Then water was added thereto, and it was filtered, dried and concentrated. Purification by column chromatography gave 2-{4-[4-(5-{2-[(methylsulphonyl)oxy]phenyl}-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidin-1-yl}-2-oxoethyl acetate (170 mg, 30%).
Reaction SMILES: [CH3:1][C:2]1[C:7]2[N:8]=[C:9]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])[O:10][C:6]=2[CH:5]=[C:4]([CH2:19][C:20](O)=[O:21])[CH:3]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH2:56][C:57]1[CH:62]=[CH:61][C:60]([C@H:63]([CH3:70])[CH2:64][C:65]([O:67][CH2:68][CH3:69])=[O:66])=[CH:59][CH:58]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1[C:7]2[N:8]=[C:9]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])[O:10][C:6]=2[CH:5]=[C:4]([CH2:19][C:20]([NH:56][C:57]2[CH:58]=[CH:59][C:60]([C@H:63]([CH3:70])[CH2:64][C:65]([O:67][CH2:68][CH3:69])=[O:66])=[CH:61][CH:62]=2)=[O:21])[CH:3]=1
Reactant: Cc1ccccc1Nc1nc2c(C)cc(CC(=O)O)cc2o1
Reactant: CCOC(=O)C[C@@H](C)c1ccc(N)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C[C@@H](C)c1ccc(NC(=O)Cc2cc(C)c3nc(Nc4ccccc4C)oc3c2)cc1
Yield: 91.5 %

Procedure:
A stirred solution of 2-(4-methyl-2-o-tolylaminobenzoxazol-6-yl)acetic acid [0.1 g, Reference Example 9(b)] in dimethylformamide (3 mL) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.128 g), diisopropylethylamine (0.22 g) and after 5 minutes with ethyl (R) 3-(4-aminophenyl)butanoate (0.107 g, Reference Example 1). After 4 hours the reaction mixture was diluted with ethyl acetate and then washed with water, then with hydrochloric acid (1M), then twice with water, then with brine, then dried and then evaporated to give the title compound (0.15 g) as a brown oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1.[C:25](#N)C.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH:23]1[C:24]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:20]=[CH:21][C:22]=1[CH2:25][N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CC#N
Reactant: c1ccc2ccccc2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CC1(C)OB(c2cnn(Cc3ccc4ccccc4c3)c2)OC1(C)C
Reaction time: 1 h

Procedure:
The 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.10 g, 0.00052 mol) was combined with naphthalene, 2-(bromomethyl)- (0.12 g, 0.00057 mol) in ACN (3.0 mL, 0.057 mol) under nitrogen at rt. Then cesium carbonate (0.50 g, 0.0015 mol) was added and the reaction was complete after stirring for 1 h. This was partitioned between ethyl acetate and brine. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to give 1-(2-naphthylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 0.17 gm, as an oil, LC/MS (M+H)+: 335, 1H NMR (CDCl3) δ 7.89 (s, 1H), 7.79-7.84 (m, 3H), 7.69 (bs, 2H), 7.49-7.4 (m, 2H), 7.46-7.33 (m, 1H), 5.47 (s, 2H), 1.31 (s, 12H).
Reaction SMILES: [F:1][CH:2]([F:5])[CH2:3][OH:4].F[C:7]1[CH:8]=[CH:9][C:10]([N+:17]([O-:19])=[O:18])=[C:11]([CH:16]=1)[C:12]([O:14][CH3:15])=[O:13].CCN(CC)CC.C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C>C1COCC1>[F:1][CH:2]([F:5])[CH2:3][O:4][C:7]1[CH:8]=[CH:9][C:10]([N+:17]([O-:19])=[O:18])=[C:11]([CH:16]=1)[C:12]([O:14][CH3:15])=[O:13]
Reactant: COC(=O)c1cc(F)ccc1[N+](=O)[O-]
Reactant: OCC(F)F
Agent: CC(C)CN1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(OCC(F)F)ccc1[N+](=O)[O-]
Reaction time: 0.5 h
Yield: 92.5 %

Procedure:
8.53 g of 2,2-difluoroethanol are added to a solution of 17.31 g of methyl 5-fluoro-2-nitrobenzoate, 9.64 g of NEt3 and 32.71 g of 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane in 250 ml of anhydrous THF. The mixture is stirred at AT for 30 min. The solvent is evaporated under reduced pressure. Water is added and extraction is carried out with AcOEt. The extract is washed with a 1N aqueous HCl solution, with water and then with a saturated NaCl solution. It is dried over MgSO4 and filtered, and the solvent is evaporated under reduced pressure to give 21 g of the expected product.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH:10]=[N:11][NH:12]3)[N:5]=[C:4]2[N:17]([CH3:20])[N:18]=[CH:19][C:3]=12.[CH3:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH:12]1[C:13]2[C:9](=[C:8]([C:6]3[N:5]=[C:4]4[N:17]([CH3:20])[N:18]=[CH:19][C:3]4=[C:2]([O:31][C:28]4[CH:27]=[CH:26][C:25]([S:22]([CH3:21])(=[O:24])=[O:23])=[CH:30][CH:29]=4)[CH:7]=3)[CH:16]=[CH:15][CH:14]=2)[CH:10]=[N:11]1
Reactant: CS(=O)(=O)c1ccc(O)cc1
Reactant: Cn1ncc2c(Cl)cc(-c3cccc4[nH]ncc34)nc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cn1ncc2c(Oc3ccc(S(C)(=O)=O)cc3)cc(-c3cccc4[nH]ncc34)nc21
Temperature: 155 °C

Procedure:
4-Chloro-6-(1H-indazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridine 7 (0.1 g, 0.352 m moles) was dissolved in 2 mL DMF. 4-Methylsulfonylphenol 8a (0.12 g, 0.704 mmol) and potassium carbonate (0.24 g, 1.76 mmol) were added. After bubbling nitrogen gas through the reaction mixture, it was heated by microwave at 155° C. for 1.5-2 hours. Solvent was removed, excess potassium carbonate was filtered and partitioned and extracted with ethyl acetate. The organic portions were washed with saturated sodium bicarbonate solution followed by brine, dried over anhydrous Na2SO4, solvent removed and purified to obtain 101. 1H NMR (400 MHz, DMSO) δ 13.26 (s, 1H), 8.77 (s, 1H), 8.06 (d, J=8.8, 2H), 7.92-7.51 (m, 6H), 7.51-7.27 (m, 2H), 4.13 (s, 3H), 3.28 (s, 3H) MS (ESI) m/z 420.1 (M+1)+
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C:3](=O)[O:2]1.ClCC1C(CC#[N:22])=CC=CC=1>>[OH:2][CH2:1][C:10]1[C:5]([CH2:4][C:3]#[N:22])=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: N#CCc1ccccc1CCl
Reactant: O=C1Cc2ccccc2CO1
Product: N#CCc1ccccc1CO
Yield: 2.2 %

Procedure:
After the completion of reaction, the concentration of 3-isochromanone was analyzed by GC analysis and then the yield of 3-isochromanone was calculated. As a result, the yield was found to be 75% based on α-chloro-α′-cyano-o-xylene. At this time, the conversion ratio of α-chloro-α′-cyano-o-xylene was 100% and the by-product α-hydroxy-α′-cyano-o-xylene was produced in a yield of 2.2%. Furthermore, as a result of the HPLC analysis, α-carboxy-α′-hydroxy-o-xylene and α-aminocarboxy-α′-hydroxy-o-xylene were found to be present as by-products in a concentration of 18% based on α-chloro-α′-cyano-o-xylene.
Reaction SMILES: [O:1]=[C:2]=[N:3]C1CC(C)(C)CC(C)(CN=C=O)C1.[C:17]([O:21]CCO)(=[O:20])[CH:18]=[CH2:19].C1(C=[CH:31][C:29]([OH:30])=CC=1)O>>[C:17]([OH:21])(=[O:20])[CH:18]=[CH2:19].[NH2:3][C:2]([O:30][CH2:29][CH3:31])=[O:1]
Reactant: Oc1ccc(O)cc1
Reactant: C=CC(=O)OCCO
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Product: C=CC(=O)O
Product: CCOC(N)=O

Procedure:
192.4 g of 1,6-hexanediol and 166.6 g of adipic acid were placed in a reaction vessel and reacted for 6 hours at 220° C. while dehydrating and condensing to obtain 318 g of polyester. 222 g (1 mole) of isophorone diisocyanate were added thereto and reacted for 2 hours at 80° C. Moreover, 116 g (1 mole) of 2-hydroxyethyl acrylate and 1.4 g of hydroquinone were further added thereto and reacted for 3 hours at 80° C. while blowing in air to obtain a urethane acrylate (C-1) having acryloyl groups on both ends of a molecule thereof.
Reaction SMILES: [N:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=1)=[N+]=[N-].[CH2:14]=[CH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>>[CH2:16]([CH:15]1[CH2:14][N:1]1[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=1)[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: [N-]=[N+]=Nc1ccc(C(F)(F)F)cc1
Reactant: C=CCCCCCC
Product: CCCCCCC1CN1c1ccc(C(F)(F)F)cc1

Procedure:
1-azido-4-(trifluoromethyl)-benzene (0.392 g, 2.09 mmol), 1-octene (3.575 g, 31.9 mmol), and [(Me,EtTCPh)Fe(NCCH3)2](PF6)2 (0.0029 g, 0.0021 mmol) were used in the General Catalytic Reaction described above yielding 0.212 g, 37.3%. 1H NMR (CDCl3, 499.74 MHz): δ 7.47 (d, J=8.0 Hz, 2H), 7.03 (d, J=8.0 Hz, 2H), 2.13 (m, 2H), 2.09 (d, J=6.0 Hz, 1H), 1.58 (m, 4H), 1.41 (m, 2H), 1.34 (m, 4H), 0.92 (t, J=6.5 Hz, 3H). 13C NMR (CDCl3, 125.66 MHz): δ 158.40, 126.27 (q, J=3.8 Hz), 124.60 (q, J=270.0 Hz), 124.19 (q, J=32.7 Hz), 120.83, 40.55, 34.23, 33.16, 31.97, 29.32, 27.71, 22.75, 14.18. 19F NMR (CDCl3, 470.2 MHz): δ −61.7. GC/MS (m/z): 271.1. DART HR MS (m/z): [M+H]+272.1609 (found). C15H21F3N, 272.1626 (calcd).
Reaction SMILES: [OH-:1].[Na+].Cl[C:4](Cl)(Cl)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:7]=1.S(=O)(=O)(O)O.[CH3:23][OH:24]>ClCCl.O>[F:13][C:12]([F:15])([F:14])[C:8]1[CH:7]=[C:6]([CH2:5][C:4]([O:24][CH3:23])=[O:1])[CH:11]=[CH:10][CH:9]=1
Reactant: FC(F)(F)c1cccc(CC(Cl)(Cl)Cl)c1
Reactant: [OH-]
Reactant: CO
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: COC(=O)Cc1cccc(C(F)(F)F)c1
Temperature: 25 °C

Procedure:
A 3.36 g. portion of flaked sodium hydroxide was slurried in 33 ml. of methanol and 1 ml. of water, and the mixture was warmed to dissolve most of the base. It was then cooled to ambient temperature and to it was added over 2-3 minutes 4 g. of 1,1,1-trichloro-2-(3-trifluoromethylphenyl)ethane. The mixture was then stirred under reflux at 70° for 4 hours, and was then cooled to 5°. To it was added about 3 ml. of concentrated sulfuric acid. A little more methanol was added to increase the fluidity of the mixture, and the mixture was stirred under reflux again for 45 minutes more. It was then cooled to ambient temperature, and diluted with about 60 ml. of water. A 35 ml. portion of dichloromethane was added, the layers were separated, and the aqueous layer was extracted with three 25 ml. portions of dichloromethane. All of the organics were combined and washed twice with 15 ml. portions of water, dried over sodium sulfate and concentrated to dryness under vacuum to obtain 2.75 g. of product, found to be 80% pure by vapor phase chromatography.
Reaction SMILES: [Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.[CH2:13](O)C=C.Cl[C:18](Cl)(Cl)[C:19]([O:21][C@H:22]1[O:35][C@H:34]([CH2:36][O:37][C:38](=[O:40])[CH3:39])[C@@H:29]([O:30][C:31](=[O:33])[CH3:32])[C@H:24]([O:25][C:26](=[O:28])[CH3:27])[C@H:23]1[NH:41][C:42](=[O:47])[C:43]([Cl:46])([Cl:45])[Cl:44])=N.CCOC(C)=O>C(Cl)Cl.C(N(CC)CC)C>[C:26]([O:25][C@H:24]1[C@H:29]([O:30][C:31](=[O:33])[CH3:32])[C@@H:34]([CH2:36][O:37][C:38](=[O:40])[CH3:39])[O:35][C@@H:22]([O:21][CH2:19][CH:18]=[CH2:13])[C@@H:23]1[NH:41][C:42](=[O:47])[C:43]([Cl:46])([Cl:45])[Cl:44])(=[O:28])[CH3:27]
Reactant: CC(=O)OC[C@H]1O[C@H](OC(=N)C(Cl)(Cl)Cl)[C@H](NC(=O)C(Cl)(Cl)Cl)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: C=CCO
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: C=CCO[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1NC(=O)C(Cl)(Cl)Cl
Temperature: -78 °C
Yield: 83.3 %

Procedure:
TMSOTf (830.0 μL, 4.6 mmol, 0.2 eq.) is added to a solution of allyl alcohol (3.1 mL, 46.0 mmol, 2 eq.) and of donor 1 (13.7 g, 23.0 mmol, 1 eq.) in DCM (160 mL), in the presence of molecular sieve 4 Å (8.9 g), stirred under argon at −78° C. After stirring for 30 min, monitoring by TLC (Tol/EtOAc, 8/2) indicates the disappearance of the donor (Rf=0.5) and the appearance of a new, more polar compound (Rf=0.35). The reaction is stopped by adding triethylamine (1 mL) and then the reaction mixture is filtered and concentrated in a rotary evaporator. The yellow oil obtained is purified by silica gel chromatography (Tol/EtOAc, 9/1→75/25) to obtain the allyl glycoside 18 as a white solid (9.4 g, 83%).
Reaction SMILES: [SH2:1].C(NCC)C.[CH3:7][C:8]1([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][O:9]1>CO>[OH:9][C:8]([CH3:7])([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][SH:1]
Reactant: S
Reactant: CCCCCC1(C)CO1
Solvent: CO
Solvent: CCNCC
Product: CCCCCC(C)(O)CS
Reaction time: 12 h

Procedure:
Pass hydrogen sulfide, with ice cooling, into 150 ml. methanol until the weight increase amounts to 3.2 g., add thereto a solution of 370 mg. diethylamine in 11 ml. methanol and subsequently 4.8 g. 2-methyl-2-pentyl-oxirane in 18 ml. methanol, again pass hydrogen sulfide into the solution for 15 minutes, leave standing for 12 hours at room temperature, distill off the solvent, dissolve the residue in 50 ml. petroleum ether (b.p. = 50°-70°), wash with water, dry over sodium sulfate and distill off the solvent to obtain as the residue, 2-hydroxy-2-methyl-heptanethiol as a colorless liquid;
Reaction SMILES: [C:1](Cl)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([NH2:17])=[N:13][NH:14]2)=[CH:10][CH:9]=1>N1C=CC=CC=1>[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([NH:17][C:1](=[O:5])[CH:2]=[CH:3][CH3:4])=[N:13][NH:14]2)=[CH:10][CH:9]=1
Reactant: Nc1n[nH]c2cc(Br)ccc12
Reactant: C/C=C/C(=O)Cl
Solvent: c1ccncc1
Product: CC=CC(=O)Nc1n[nH]c2cc(Br)ccc12
Temperature: 3 °C
Reaction time: 12 h

Procedure:
1.07 cm3 of crotonyl chloride are added to 2 g of 6-bromo-1H-indazole-3-amine, prepared previously, in 30 cm3 of pyridine, cooled to about 3° C. The medium is allowed to return to about 19° C. over 12 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50° C.) and the residue is taken up in 20 cm3 of ethyl acetate and 20 cm3 of distilled water. The aqueous phase is re-extracted with 20 cm3 of ethyl acetate. The aqueous phases are combined and then evaporated under the conditions described previously. The residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (50/50 by volume) and collecting 15 cm3 fractions. The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). After drying (90 Pa; 45° C.), 130 mg of N-(6-bromo-1H-indazol-3-yl)-2-butenamide (E form) are obtained in the form of a beige-coloured solid melting at 232° C.