Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[N:9]2[C:5](=[N:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)[S:4][N:3]=1.[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1>ClCCl>[N:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[NH:14][C:2]1[N:9]2[C:5](=[N:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)[S:4][N:3]=1
Reactant: Nc1ccccn1
Reactant: Brc1nsc2nc3ccccc3n12
Solvent: ClCCl
Product: c1ccc(Nc2nsc3nc4ccccc4n23)nc1
Reaction time: 48 h
Yield: 83.1 %

Procedure:
To a cooled solution of 3-bromo-1,2,4-thiadiazolo[4,5-a]benzimidazole (0.30 g, 1.17 mmol) in 15 mL of dichloromethane, 2-aminopyridine (0.276 g, 2.93 mmol) was added dropwise and the mixture was allowed to stir for 48 h. The reaction mixture wad diluted with 100 mL of dichloromethane and washed with water (2×30 mL) and then brine (1×25 mL). The organic layer was dried over magnesium sulfate and evaporated to give a yellow solid (0.26 g, 83%) 1H-NMR (CDCl3) δ 6.59 (apparent 5, 1H, pyr-H), 7.12 (apparent br. d, 1H, pyr-H), 7.28 (t, 1H, ArH), 7.38 (t, 1H, ArH), 7.51 (m, 2H, ArH & pyr-H), 7.70 (d, 1H, ArH), 8.28 (d, 1H, pyr-H); m.p. 155.5-157° C.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.Cl[CH2:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]2[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH3:30])=[C:23]([O:31][CH3:32])[CH:22]=2)[CH:16]=1>>[CH2:11]([O:10][C:8]([N:5]1[CH2:4][CH2:3][CH:2]([NH:1][CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([C:21]3[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH3:30])=[C:23]([O:31][CH3:32])[CH:22]=3)[CH:16]=2)[CH2:7][CH2:6]1)=[O:9])[CH3:12]
Reactant: COc1cc(-c2cc(CCl)ccn2)cc(OC)c1OC
Reactant: CCOC(=O)N1CCC(N)CC1
Product: CCOC(=O)N1CCC(NCc2ccnc(-c3cc(OC)c(OC)c(OC)c3)c2)CC1

Procedure:
4-Amino-1-(ethoxycarbonyl)piperidine (341 mg) and 4-chloromethyl-2-( 3,4,5-trimethoxyphenyl)pyridine (300 mg) were condensed in the same manner as described in Example 2 to give the title compound.
Reaction SMILES: [CH3:1][Si:2]([CH3:18])([CH3:17])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6]2.[CH3:19][C:20]1[CH:21]=[C:22]([CH2:26]O)[CH:23]=[CH:24][CH:25]=1.C(C=P(CCCC)(CCCC)CCCC)#N>>[CH3:1][Si:2]([CH3:17])([CH3:18])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=1)[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6]2
Reactant: CCOC(=O)c1cc2cc([Si](C)(C)C)ccc2[nH]1
Reactant: Cc1cccc(CO)c1
Agent: CCCCP(=CC#N)(CCCC)CCCC
Product: CCOC(=O)c1cc2cc([Si](C)(C)C)ccc2n1Cc1cccc(C)c1

Procedure:
This compound was prepared according to a process similar to that described in step 5.1 by reacting ethyl 5-trimethylsilyl-1H-indole-2-carboxylate prepared according to the process described in step 10.4 with (3-methylphenyl)methanol in the presence of (cyanomethylene)tributylphosphorane (CMBP). The crude reaction product is then purified by flash chromatography on a column of silica gel to give the expected product.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl-].[CH3:12][O:13][CH2:14][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.N#N.[CH2:36]([O:43][C:44]([CH:46]1[CH2:51][CH2:50][CH:49]([CH:52]=O)[CH2:48][CH2:47]1)=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>O1CCCC1>[CH2:36]([O:43][C:44]([CH:46]1[CH2:47][CH2:48][CH:49]([CH:52]=[CH:12][O:13][CH3:14])[CH2:50][CH2:51]1)=[O:45])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: O=CC1CCC(C(=O)OCc2ccccc2)CC1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: N#N
Agent: [Cl-]
Solvent: C1CCOC1
Product: COC=CC1CCC(C(=O)OCc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
NaHMDS (1.0 M in THF) (466 μL, 466 μmol) was added to a solution of methoxymethyltriphenylphosphonium chloride (160 mg, 466 μmol) in tetrahydrofuran (3.88 mL) at 0° C. in an N2 atmosphere, and the mixture was stirred at 0° C. for one hour. A solution of 4-formyl-cyclohexanecarboxylic acid benzyl ester (cis-trans=4:1 mixture) (95.6 mg, 388 μmol) in tetrahydrofuran (2.00 mL) was added dropwise to the reaction solution at 0° C., and the mixture was stirred for 30 minutes. Thereafter, the reaction mixture was stirred at room temperature for 20 hours and quenched with a saturated aqueous ammonium chloride solution (5 mL). H2O (20 mL) was then added, followed by extraction with dichloromethane (50 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 4-(2-methoxy-vinyl)-cyclohexanecarboxylic acid benzyl ester (trans-cis=4:1 and E-Z=2:1 mixture) as a yellow oily substance (49.7 mg, 47%).
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[O:31][C:30]([CH3:32])=[N:29][C:28]=1[C:33](O)=[O:34]>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[C:16]([NH:18][C:33]([C:28]3[N:29]=[C:30]([CH3:32])[O:31][C:27]=3[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[O:20][CH3:19])=[O:34])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2ccc(Cn3cc(N)cn3)o2)OCCO1
Reactant: COc1ccccc1-c1oc(C)nc1C(=O)O
Product: COc1ccccc1-c1oc(C)nc1C(=O)Nc1cnn(Cc2ccc(C(C)=O)o2)c1

Procedure:
Following general procedure B followed by either C or D, 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-4-ylamine and 5-(2-methoxy-phenyl)-2-methyl-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=0.92 min; [M+H]+=421.00.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].CC1C2C(=CC3C(C=2)=CC=CC=3)C=CC=1.C(OCCCO)(=O)C(C)=C.C(OCC)(=O)C(C)=C.C([O:43][CH:44]([CH3:48])[CH2:45]OC)(=O)C>>[CH3:45][CH:44]([OH:43])[CH2:48][O:5][C:1]([C:2]([CH3:4])=[CH2:3])=[O:6]
Reactant: C=C(C)C(=O)O
Reactant: COCC(C)OC(C)=O
Agent: C=C(C)C(=O)OCC
Agent: C=C(C)C(=O)OCCCO
Agent: Cc1cccc2cc3ccccc3cc12
Product: C=C(C)C(=O)OCC(C)O
Temperature: 40 °C

Procedure:
A polymer feed solution was prepared by combining 30.76 g methylanthracene methacrylate monomer, 16.6 g 3-hydroxypropyl methacrylate monomer, 16.0 g ethyl methacrylate, and 50 g propylene glycol monomethyl ether acetate (PGMEA) in a 250 ml three neck, round-bottom flask fitted with a mechanical stirrer, thermal controller, thermal probe, heating mantle and nitrogen purge inlet (sweep). The reaction mixture was heated until the temperature of the reaction mixture reached 80° C. 16.15 g PGMEA solution containing 10 wt % Vazo 67 azo initiator (white powder, Dupont) was next added to the flask. The flask was heated until the temperature of the reaction mixture reached 90° C. and maintained for 8 hours with stirring. Heating was stopped and the reactor was allowed to cool down to 40° C. The resulting polymer solution was precipitated with methyl alcohol (10× excess of reaction mixture), filtered and vacuum dried, to provide Poly(ANTMA-co-HPMA-co-EMA) polymer [Mw=8K; PDI=2.5; ANTMA:HPMA; EMA=30:30:40 mol %, by 13C-NMR].
Reaction SMILES: [C:1]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].C([O-])([O-])=O.[K+].[K+].Cl[C:18]1[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][C:21]([N+:28]([O-:30])=[O:29])=[CH:20][N:19]=1>C1COCC1>[C:1]([CH:3]([C:18]1[C:23]([C:24]([F:26])([F:27])[F:25])=[CH:22][C:21]([N+:28]([O-:30])=[O:29])=[CH:20][N:19]=1)[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2]
Reactant: O=[N+]([O-])c1cnc(Cl)c(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)CC#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)C(C#N)c1ncc([N+](=O)[O-])cc1C(F)(F)F
Reaction time: 10 h
Yield: 97.7 %

Procedure:
To a solution of tert-butyl 2-cyanoacetate (523 mg, 3.71 mmol) in THF (15 mL) was added K2CO3 (854 mg, 6.18 mmol). Then 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (700 mg, 3.09 mmol) was added into the mixture and the mixture was at 50° C. for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative TLC (DCM/MeOH=20:1, Rf=0.4) to yield a light yellow solid of tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate (1 g, 3.02 mmol, 98.0% yield): 1H NMR (400 MHz, CD3OD) δ 8.99 (d, J=2.43 Hz, 1H), 8.36 (d, J=2.43 Hz, 1H), 3.35 (s, 1H), 1.49 (d, J=1.54 Hz, 9H); ES-LCMS m/z 276 (M-55).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([O:11]C)=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[CH3:13][N:14]([CH3:26])[C:15]([C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1)=[O:16].C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:3]([C:9]([OH:11])=[O:10])=[N:4][C:5]([C:20]2[CH:21]=[CH:22][C:17]([C:15](=[O:16])[N:14]([CH3:13])[CH3:26])=[CH:18][CH:19]=2)=[CH:6][N:7]=1
Reactant: CN(C)C(=O)c1ccc(B(O)O)cc1
Reactant: COC(=O)c1nc(Br)cnc1N
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CN(C)C(=O)c1ccc(-c2cnc(N)c(C(=O)O)n2)cc1
Temperature: 25 °C
Yield: 32.6 %

Procedure:
Methyl 3-amino-6-bromo-pyrazine-2-carboxylate (6.01 g, 25.9 mmol, 1.0 Eq.), 4-(dimethylcarbamoyl)phenylboronic acid (5.00 g, 25.9 mmol, 1.0 Eq.), Na2CO3 (5.49 g, 51.8 mmol, 2.0 Eq.) and Pd(PPh3)4 (2.99 g, 2.59 mmol, 0.1 Eq.) in acetonitrile (30 mL) and water (30 mL) were heated at 90° C. for 16 hours. After cooling to ambient temperature the precipitate was removed by filtration. The aqueous filtrate was acidified to pH4 by addition of 1M HCl and then extracted with dichloromethane (3×20 mL), dried over MgSO4 and concentrated in vacuo to give the sub-title product as a yellow solid (2.42 g, 65% Yield). 1H NMR (400.0 MHz, DMSO) δ 2.95 (3H, br s), 3.00 (3H, br s), 7.49-7.51 (2H, m), 7.58 (2H, br s), 8.15 92H, d), 8.95 (1H, s), 13.25 (1H, br s) ppm; MS (ES+) 287.13.
Reaction SMILES: [C:1]([O:4][CH2:5][C@@H:6]1[CH2:11][C@@H:10]([OH:12])[CH2:9][CH:8]([OH:13])[O:7]1)(=[O:3])[CH3:2].C(=O)([O-])[O-].[Ba+2].BrBr.[Na+].[Cl-]>O>[C:1]([O:4][CH2:5][C@@H:6]1[CH2:11][C@@H:10]([OH:12])[CH2:9][C:8](=[O:13])[O:7]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@@H]1C[C@@H](O)CC(O)O1
Agent: BrBr
Agent: O=C([O-])[O-]
Agent: [Ba+2]
Solvent: O
Product: CC(=O)OC[C@@H]1C[C@@H](O)CC(=O)O1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The solution of ((2S,4R)-4,6-dihydroxytetrahydro-2H-pyran-2-yl)methyl acetate (IV) (1 eq) in water was cooled down to 0° C. Barium carbonate (1.4 eq) was added followed by a dropwise addition of Br2 (1.2 eq) and the reaction was stirred overnight at room temperature. The solution was saturated with NaCl and extracted four times with EtOAc. The combined organic phases were dried over MgSO4 and concentrated. The purification using flash chromatography (hexane/acetone=75/25 to 55/45) furnished ((2S,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)methyl acetate (V).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:24]=[C:11]2[CH:12]=[C:13]([C:16]3[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=3)[CH:19]=[O:20])[CH:14]=[CH:15][N:10]2[N:9]=1.[C:25]([Mg]Br)#[CH:26]>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:24]=[C:11]2[CH:12]=[C:13]([C:16]3[CH:17]=[C:18]([CH:19]([OH:20])[C:25]#[CH:26])[CH:21]=[CH:22][CH:23]=3)[CH:14]=[CH:15][N:10]2[N:9]=1
Reactant: O=Cc1cccc(-c2ccn3nc(-c4ccccc4F)cc3c2)c1
Reactant: C#C[Mg]Br
Solvent: C1CCOC1
Product: C#CC(O)c1cccc(-c2ccn3nc(-c4ccccc4F)cc3c2)c1
Yield: 81.8 %

Procedure:
The procedure described in stage 2.5 is followed, starting with 0.125 g (0.40 mmol) of 3-[2-(2-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl]benzaldehyde obtained in stage 7.2, in solution in 15 ml of tetrahydrofuran, followed by addition of 3.50 ml (1.75 mmol) of an ethynylmagnesium bromide solution (0.5M in tetrahydrofuran) and after chromatography on silica gel, elution being carried out with a mixture of cyclohexane and ethyl acetate (8/2), 0.112 g (82%) of the expected product is obtained in the fatm of a beige powder.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=1.[CH:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[CH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[CH:11][C:2]=1[CH:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[OH:19]
Reactant: Brc1ccc2ccccc2c1
Reactant: O=Cc1ccccc1
Product: OC(c1ccccc1)c1ccc2ccccc2c1

Procedure:
Using general procedure B, 2-bromonaphthalene was reacted with benzaldehyde to give naphthalen-2-yl-phenyl-methanol as a colorless solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([F:12])=[C:7]([OH:13])[CH:6]=[CH:5]2.[CH3:14][C:15]1[CH:16]=[C:17]([CH:22]=[CH:23][C:24]=1B1OC(C)(C)C(C)(C)O1)[C:18]([O:20]C)=[O:19]>>[F:12][C:8]1[C:7]([OH:13])=[CH:6][CH:5]=[C:4]2[C:9]=1[CH:10]=[CH:11][C:2]([C:24]1[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]=1[CH3:14])=[CH:3]2
Reactant: COC(=O)c1ccc(B2OC(C)(C)C(C)(C)O2)c(C)c1
Reactant: Oc1ccc2cc(Br)ccc2c1F
Product: Cc1cc(C(=O)O)ccc1-c1ccc2c(F)c(O)ccc2c1

Procedure:
Followed the coupling procedure described in Example 29 starting from 6-bromo-1-fluoronaphthalen-2-ol (Intermediate 13) and methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate. 1H-NMR (DMSO-d6, 300 MHz, TMS): δ 12.90 (b, 1H), 10.17 (b, 1H), 7.84-7.97 (m, 4H), 7.70 (d, 1H), 7.54 (d, 1H), 7.41 (d, 1H), 7.30 (t, 1H), 2.33 (s, 3H). MS (ESI): m/z=295.25 [MA]−.
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([CH:16]=[C:17]([O:19][CH:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[CH:18]=2)[C:12]([O:14]C)=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.O.[OH-].[Li+]>C1COCC1.O>[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([CH:16]=[C:17]([O:19][CH:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[CH:18]=2)[C:12]([OH:14])=[O:13])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)c1cc(OCc2ccccc2)cc(OC2CCOCC2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cc(OCc2ccccc2)cc(OC2CCOCC2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
Methyl 3-[(phenylmethyl)oxy]-5-(tetrahydro-2H-pyran-4-yloxy)benzoate (9.00 g, 26.3 mmol) was dissolved in THF (120 mL) and methanol (30 mL) added a solution of lithium hydroxide monohydrate (3.24 g, 78.9 mmol) in water (60 mL). The bi-phasic solution was stirred at RT for 3 hours until complete conversion was indicated by LCMS. The organics were removed in vacuo and water (40 mL) added. The pH of the mixture was adjusted to 7 by the addition of hydrochloric acid and the resulting precipitate filtered and washed with cold water to give the desired compound as a white solid (8.03 g). 1H NMR δ (d6-DMSO): 1.57 (m, 2H), 1.94 (m, 2H), 3.50 (m, 2H), 3.84 (m, 2H), 4.62 (m, 1H), 5.15 (s, 2H), 6.87 (t, 1H), 7.09 (m, 1H), 7.14 (m, 1H), 7.34 (t, 1H), 7.40 (t, 2H), 7.46 (d, 2H), 12.99 (s, 1H); m/z 327 (M+H)+
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]([C:36]1[CH:41]=[CH:40][N:39]=[CH:38][N:37]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13]([O:17][C@H:18]2[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]2[C:24]2[CH:25]=[N:26][N:27](C3CCCCO3)[CH:28]=2)=[CH:12][C:11]=1[F:35])(=[O:9])=[O:8].C([SiH](CC)CC)C.FC(F)(F)C(O)=O.ClCCl>CO>[F:35][C:11]1[CH:12]=[C:13]([O:17][C@H:18]2[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]2[C:24]2[CH:25]=[N:26][NH:27][CH:28]=2)[C:14]([F:16])=[CH:15][C:10]=1[S:7]([NH:6][C:36]1[CH:41]=[CH:40][N:39]=[CH:38][N:37]=1)(=[O:8])=[O:9]
Reactant: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2cc(F)c(O[C@H]3CCCC[C@@H]3c3cnn(C4CCCCO4)c3)cc2F)c(OC)c1
Agent: CC[SiH](CC)CC
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=S(=O)(Nc1ccncn1)c1cc(F)c(O[C@H]2CCCC[C@@H]2c2cn[nH]c2)cc1F
Yield: 125.3 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 22c by using the N-(2,4-dimethoxybenzyl)-2,5-difluoro-(N-pyrimidin-4-yl)-4-({(1S*,2R*)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]cyclohexyl}oxy)benzenesulfonamide (302 mg, 0.451 mmol) prepared in Example 33c, triethylsilane (0.40 mL), trifluoroacetic acid (4.0 mL), dichloromethane (4.0 mL) and methanol (4.0 mL), to yield the title compound (246 mg, 55%) as a colorless solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[NH:13][C:12]([C:14]([C:46]4[CH:51]=[CH:50][C:49]([OH:52])=[CH:48][CH:47]=4)=[C:15]4[N:45]=[C:18]([C:19]([C:38]5[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=5)=[C:20]5[NH:37][C:23](=[C:24]([C:30]6[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=6)[C:25]6[CH:26]=[CH:27][C:28]=2[N:29]=6)[CH:22]=[CH:21]5)[CH:17]=[CH:16]4)=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH3:72].O>CN(C=O)C>[OH:52][C:49]1[CH:48]=[CH:47][C:46]([C:14]2[C:12]3[NH:13][C:9]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([O:1][CH2:72][CH2:71][CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65][CH2:64][CH2:63][CH2:62][CH2:61][CH3:60])=[CH:3][CH:4]=4)=[C:28]4[N:29]=[C:25]([C:24]([C:30]5[CH:31]=[CH:32][C:33]([OH:36])=[CH:34][CH:35]=5)=[C:23]5[NH:37][C:20](=[C:19]([C:38]6[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=6)[C:18]6[CH:17]=[CH:16][C:15]=2[N:45]=6)[CH:21]=[CH:22]5)[CH:26]=[CH:27]4)=[CH:10][CH:11]=3)=[CH:51][CH:50]=1
Reactant: Oc1ccc(-c2c3nc(c(-c4ccc(O)cc4)c4ccc([nH]4)c(-c4ccc(O)cc4)c4nc(c(-c5ccc(O)cc5)c5ccc2[nH]5)C=C4)C=C3)cc1
Reactant: CCCCCCCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCCCCCCOc1ccc(-c2c3nc(c(-c4ccc(O)cc4)c4ccc([nH]4)c(-c4ccc(O)cc4)c4nc(c(-c5ccc(O)cc5)c5ccc2[nH]5)C=C4)C=C3)cc1
Temperature: 25 °C

Procedure:
5,10,15,20-tetrakis-(4-Hydroxy-phenyl)-porphyrin (400 mg, 0.59 mmol) is dissolved and K2CO3 (1.0 g, 7.1 mmol) is suspended in DMF (75 mL). To the vigorously stirred reaction mixture a solution of 1-bromotridecane (0.1 mL, 0.45 mmol) in DMF (10 mL) is added dropwise at 50° C. during 30 mins and the mixture is then heated for 1.5 h. The reaction mixture is cooled to room temperature and poured into water (150 mL). The porphyrins are extracted with ethyl acetate (100 mL) and the extract washed with brine (3×50 mL) and dried (Na2SO4). After evaporation of solvent, the residue is dissolved in toluene:ethanol (1:1, by vol., ca. 10 mL) and purified by chromatography using a column (200 g) of silica gel (Merck 60) with toluene as the eluent. After the elution of the first three compounds, the eluent is changed to toluene:ethyl acetate (2:1, by vol.). The fifth compound eluted is collected and dried under high vacuum to yield product as violet crystals.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([NH:12][C@H:13]1[C:17](=[O:18])[N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:15][C@H:14]1[C:25]([O:27]CC)=[O:26])=[O:11].[OH-].[Li+].O>CCO.C1COCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([NH:12][C@@H:13]1[C:17](=[O:18])[N:16]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:15][C@H:14]1[C:25]([OH:27])=[O:26])=[O:11]
Reactant: CCOC(=O)[C@@H]1CN(c2ccccc2)C(=O)[C@@H]1NC(=O)c1cc2ccccc2[nH]1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: O=C(N[C@@H]1C(=O)N(c2ccccc2)C[C@H]1C(=O)O)c1cc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 16 h
Yield: 42.7 %

Procedure:
To the ethyl ester of Example 4 (68 mg, 0.174 mmol) dissolved in 4:1 EtOH/THF was added an aqueous solution of lithium hydroxide (13 mg, 0.521 mmol). After stirring for 16 h at room temperature, 2.5 ml of water was added and the solution was extracted with chloroform. The aqueous layer was then acidified with 1N HCl to pH2 and extracted again with chloroform. The combined organic layers were dried over MgO4, filtered and concentrated in vacuo to give the crude acid which was chromatographed on silica gel eluting with 5/95/1 EtOH/CH2Cl2 /HOAc to give the title compound (27 mg, 42%) as a colorless powder. Anal calcd for C20H17N3O4 : C, 64.51; H, 4.87; N, 11.28. Found: C, 64.26; H, 4.62; N, 10.88. MS M+1 calcd for C20H17N3O4 364, found 364.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7](Cl)=[O:8].[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1COCC1>[C:11]1([NH:10][C:7](=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Br:1])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(Cl)CCCCCBr
Reactant: Nc1ccccc1
Solvent: C1CCOC1
Product: O=C(CCCCCBr)Nc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 6-bromohexanoyl chloride (1.00 mL, 6.53 mmol) in THF (35 mL) at 0° C. was added dropwise a solution of aniline (0.60 mL, 6.53 mmol) and TEA (1.09 mL, 7.84 mmol) in THF (5 mL). The reaction mixture was allowed to warm to ambient temperature and stirred for 2 h. The mixture was filtered, the solids rinsed with EtOAc, and the filtrate reduced under vacuum. The residue was partitioned between H2O (15 mL) and EtOAc (20 mL) and the layers separated. The aqueous portion was extracted with EtOAc (3×10 mL) and the organic layers combined, washed with HCl (1 N), brine, dried over MgSO4, and filtered. Concentration under reduced pressure left a brown oil which was passed through a plug of silica gel (30% EtOAc/hexanes) under aspiration. Concentration under reduced pressure left 67 as a solid (1.55 g, 5.74 mmol, 88%). TLC Rf 0.36 (25% EtOAc/hexanes); 1H-NMR (400 MHz, DMSO-d6) δ 9.85 (s, 1H), 7.57 (d, 2H), 7.27 (t, 2H), 7.01 (t, 1H), 3.53 (t, 2H), 2.30 (t, 2H), 1.81 (t, 2H), 1.63 (m, 2H), 1.42 (m, 2H); MS (ESI+) calcd for C12H16BrNO 268+270, found 269+271 [M+H]+.
Reaction SMILES: [O-:1][C:2]#[N:3].[K+].[C:5]([NH:10][NH2:11])([CH2:8][CH3:9])([CH3:7])[CH3:6].Cl>O>[C:5]([NH:10][NH:11][C:2]([NH2:3])=[O:1])([CH2:8][CH3:9])([CH3:7])[CH3:6]
Reactant: CCC(C)(C)NN
Reactant: N#C[O-]
Agent: Cl
Agent: [K+]
Solvent: O
Product: CCC(C)(C)NNC(N)=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
13.6 g of potassium cyanate are added to a mixture of 17 g of tert-pentylhydrazine and 30 ml of water cooled in an ice bath and 16.5 g of conc. hydrochloric acid are then added dropwise. The mixture is stirred at room temperature for 3 h and the solid is filtered off with suction, washed with water and dried in vacuo.
Reaction SMILES: [C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=[O:24])=[CH:18][C:17]=3[Br:26])[CH2:10]2)=[C:6]([CH2:29][CH2:30][CH3:31])[C:5]=1[OH:32])(=[O:3])[CH3:2].[C:33](C1C=CC(O[C@@H]2CCC[C@H](OS(C)(=O)=O)C2)=C(CCC)C=1O)(=O)C>>[C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]([O:25][CH3:33])=[O:24])=[CH:18][C:17]=3[Br:26])[CH2:10]2)=[C:6]([CH2:29][CH2:30][CH3:31])[C:5]=1[OH:32])(=[O:3])[CH3:2]
Reactant: CCCc1c(O[C@H]2CCC[C@H](Oc3ccc(CC(=O)O)cc3Br)C2)ccc(C(C)=O)c1O
Reactant: CCCc1c(O[C@@H]2CCC[C@H](OS(C)(=O)=O)C2)ccc(C(C)=O)c1O
Product: CCCc1c(O[C@@H]2CCC[C@H](Oc3ccc(CC(=O)OC)cc3Br)C2)ccc(C(C)=O)c1O

Procedure:
By following Step E of Example 8, but substituting the title compound of Step D of Example 8 for the title compound of Step C of Example 8, the title compound of this step was obtained as an oil.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.C=O.[OH-].[Na+].[C:14](OCC)(=[O:16])C>CN(C)C=O>[OH:16][CH2:14][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1
Reactant: CCOC(C)=O
Reactant: c1ccc2[nH]nnc2c1
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: OCn1nnc2ccccc21

Procedure:
A slurry of benzotriazole (11.9 g) and 30% formalin (8.3 ml) was heated to reflux in 100 ml of 25% aqueous dimethylformamide. A trace of starting material remained. The solution was treated with 1.0 ml of 10% aqueous sodium hydroxide and heated to reflux again. An aqueous ethyl acetate extractive work up afforded 1-(hydroxymethyl)benzotriazole (8.65 g).