Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.Br.[NH2:36][CH:37]1[CH2:46][CH2:45][CH2:44][C:43]2[C:42]([OH:47])=[CH:41][CH:40]=[CH:39][C:38]1=2.C(N(CC)CC)C>O1CCCC1>[C:1]([NH:36][CH:37]1[CH2:46][CH2:45][CH2:44][C:43]2[C:42]([OH:47])=[CH:41][CH:40]=[CH:39][C:38]1=2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC1CCCc2c(O)cccc21
Reactant: O=C(O)c1ccccc1
Agent: Br
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(NC1CCCc2c(O)cccc21)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
50 mmol of benzoic acid and 50 mmol of 1-hydroxybenzotriazole (HOBT) are taken in 200 ml of absolute tetrahydrofuran at 0° C. 55 mmol of dicyclohexylcarbodiimide (DCC) are added under N2 and the mixture is stirred at 0° C. for 1 hour and then at room temperature for 1 hour. 50 mmol of 5-amino-1-hydroxy-5,6,7,8-tetrahydro-naphthalene hydrobromide and 50 mmol of triethylamine are added to this solution and the mixture is stirred at room temperature for 6 hours.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]([C:26]2[CH:35]=[CH:34][C:29]3[O:30][CH2:31][CH2:32][O:33][C:28]=3[CH:27]=2)=[O:25])[CH2:19][C@@H:18]1[C:36](O)=[O:37])=[O:16])([CH3:13])([CH3:12])[CH3:11].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[NH2:9][C:4]1[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][C:5]=1[NH:8][C:36]([C@H:18]1[CH2:19][C@H:20]([NH:23][C:24]([C:26]2[CH:35]=[CH:34][C:29]3[O:30][CH2:31][CH2:32][O:33][C:28]=3[CH:27]=2)=[O:25])[CH2:21][CH2:22][N:17]1[C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])=[O:37]
Reactant: Cc1ccc(N)c(N)c1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](NC(=O)c2ccc3c(c2)OCCO3)C[C@@H]1C(=O)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: Cc1ccc(NC(=O)[C@H]2C[C@H](NC(=O)c3ccc4c(c3)OCCO4)CCN2C(=O)OC(C)(C)C)c(N)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.2 %

Procedure:
4-Methylbenzene-1,2-diamine (1.65 g, 13.5 mmol) was added to a mixture of (2R,4R)-1-(tert-butoxycarbonyl)-4-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)piperidine-2-carboxylic acid (5.0 g, 12 mmol), BOP (5.71 g, 12.9 mmol) and DIEA (4.3 mL, 24.6 mmol) in DMF (30 mL), and the resulting solution was stirred at room temperature for 8 hours. Water (100 mL) was added to the reaction mixture and then extracted with ethyl acetate (2×100 mL). The organic layers were dried over MgSO4 and concentrated to give a red solid. Purification was done by Companion (ReadySep, 120 g, silica gel packed) with methanol/methylenechloride from 1-5% to give the title compound as a brown solid 4.85 g (80%). LC-MS: 511.2 (t=2.4 min).
Reaction SMILES: C([O:4][C:5](=[O:17])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH:14]([CH3:16])[CH3:15])[CH:8]=1)(C)C.[OH-].[Na+]>C(O)C.O>[CH:14]([O:13][C:9]1[CH:8]=[C:7]([CH2:6][C:5]([OH:17])=[O:4])[CH:12]=[CH:11][CH:10]=1)([CH3:16])[CH3:15]
Reactant: CC(C)OC(=O)Cc1cccc(OC(C)C)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)Oc1cccc(CC(=O)O)c1
Reaction time: 18 h

Procedure:
Combine 3-isopropoxy-phenyl-acetic acid isopropyl ester 10.2 g, 43.2 mmol) and sodium hydroxide (2.08 g, 51.8 mmol) in 1/1 ethanol/water (80 mL). Heat to reflux. After 18 hours, remove the ethanol by evaporation in vacuo and acidify to pH=1 using an aqueous solution with 1M hydrochloric acid solution. Extract the aqueous solution 3 times with ethyl acetate. Extract the combined organic layers with water and saturated sodium chloride solution. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to obtain 3-isopropoxy-phenyl-acetic acid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][O:8][C:9]2[C:13]3[C:14]([O:18][CH:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[CH:15][CH:16]=[CH:17][C:12]=3[O:11][N:10]=2)[CH2:3][CH2:2]1.[CH:25]([C:27]1([C:33]([O:35][CH3:36])=[O:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)=O.C(C1(C(OC)=O)CCC1)=O>>[O:22]1[CH2:23][CH2:24][CH:19]([O:18][C:14]2[C:13]3[C:9]([O:8][CH2:7][CH:4]4[CH2:3][CH2:2][N:1]([CH2:25][C:27]5([C:33]([O:35][CH3:36])=[O:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)[CH2:6][CH2:5]4)=[N:10][O:11][C:12]=3[CH:17]=[CH:16][CH:15]=2)[CH2:20][CH2:21]1
Reactant: c1cc(OC2CCOCC2)c2c(OCC3CCNCC3)noc2c1
Reactant: COC(=O)C1(C=O)CCOCC1
Agent: COC(=O)C1(C=O)CCC1
Product: COC(=O)C1(CN2CCC(COc3noc4cccc(OC5CCOCC5)c34)CC2)CCOCC1

Procedure:
The title compound was prepared according to the procedure described in Step 3 of EXAMPLE 2 using 3-(piperidin-4-ylmethoxy)-4-(tetrahydro-2H-pyran-4-yloxy)-1,2-benzisoxazole (EXAMPLE 27, Step 1) and methyl 4-formyltetrahydro-2H-pyran-4-carboxylate (EXAMPLE 18, Step 1) instead of 3-(piperidin-4-ylmethoxy)-4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazole and methyl 1-formylcyclobutanecarboxylate.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.I[C:38]1[CH:39]=[C:40]([CH3:44])[CH:41]=[CH:42][CH:43]=1>>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([CH3:44])[CH:39]=2)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1ccc(I)cc1[N+](=O)[O-]
Reactant: Cc1cccc(I)c1
Agent: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Product: Cc1cccc(-c2ccc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])c2)c1

Procedure:
Prepared from (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example A1), bis(pinacolato)diboron and 3-iodotoluene according to the general procedure C. Obtained as a yellow solid (524 mg).
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][N:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][NH:3]1
Reactant: CC1=NCCc2ccccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: CC1NCCc2ccccc21

Procedure:
In close analogy to the procedure described above, 1-methyl-3,4-dihydro-isoquinoline is reacted with sodium triacetoxyborohydride to provide the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8](Cl)=[N:9]2)=[CH:4][CH:3]=1.[CH3:13][N:14]1[CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=[N:15]1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.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>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8]([C:17]3[CH:16]=[N:15][N:14]([CH3:13])[CH:18]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: Clc1cnc2ccc(Br)cc2n1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
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: COCCOC
Solvent: O
Product: Cn1cc(-c2cnc3ccc(Br)cc3n2)cn1
Yield: 82.1 %

Procedure:
Under N2, 7-bromo-2-chloro-quinoxaline (20 g; 82.1 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (17.1 g; 82.1 mmol), 2M sodium carbonate aqueous solution (41.1 mL; 82.1 mmol) in ethylene glycol dimethyl ether (200 mL) were degassed by bubbling nitrogen through for 15 minutes. Tetrakis(triphenylphosphine)palladium (0) (0.95 g; 0.82 mmol) was added and heated at reflux for 15 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was dried over MgSO4, filtered and evaporated to dryness to give 29.9 g. The crude compound was purified by chromatography over silica gel (Irregular SiOH, 20-45 μm, 1000 g MATREX; mobile phase 0.1% NH4OH, 98% DCM, 2% CH3OH). The pure fractions were collected and concentrated till dryness to give 19.5 g (82%) of 7-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-quinoxaline. MP=172° C.
Reaction SMILES: [Si:1]([O:8][CH:9]([CH2:30][C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=1)/[CH:10]=[CH:11]/[C@H:12]1[CH:16]=[CH:15][C:14](=[O:17])[C@@H:13]1[CH2:18][CH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>C1(C)C=CC=CC=1>[Si:1]([O:8][CH:9]([CH2:30][C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=1)/[CH:10]=[CH:11]/[C@H:12]1[CH2:16][CH2:15][C:14](=[O:17])[C@@H:13]1[CH2:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:28][CH:29]=1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc(CC[C@H]2C(=O)C=C[C@@H]2/C=C/C(Cc2ccc3ccccc3c2)O[Si](C)(C)C(C)(C)C)cc1
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(Cc2ccc3ccccc3c2)O[Si](C)(C)C(C)(C)C)cc1
Temperature: -40 °C
Reaction time: 1 h
Yield: 81.7 %

Procedure:
A solution of methyl 4-(2-((1R,2S)-2-((E)-3-((tert-butyldimethylsilyl)oxy)-4-(naphthalen-2-yl)but-1-en-1-yl)-5-oxocyclopent-3-en-1-yl)ethyl)benzoate (111 mg, 0.20 mmol) in toluene (1.6 mL) was added dropwise by cannula to a −40° C. mixture of [Ph3PCuH]6 (205 mg, 0.11 mmol) in toluene (9.8 mL), rinsing with 0.4 mL toluene. The reaction was stirred at −40° C. for 1 h and then at room temperature overnight. Saturated NH4Cl solution (20 mL) was added and the resulting mixture was extracted with ethyl acetate (3×20 mL). The combined organic solution was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography (ethyl acetate/hexanes) gave the title compound (91 mg, 82%).
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[C@@H:16]3[CH2:20][C@H:19]([NH:21][C:22](=[O:25])[CH2:23][CH3:24])[C@@H:18]([OH:26])[C@H:17]3[OH:27])=[C:9]([NH:28][CH2:29][CH:30]([C:38]3[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=3)[C:31]3[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=3)[N:8]=2)[CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[C:51]1([O:57][C:58](Cl)=[O:59])[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>CN1C(=O)CCC1>[C:51]1([O:57][C:58](=[O:59])[NH:1][C@@H:2]2[CH2:6][CH2:5][N:4]([C:7]3[N:15]=[C:14]4[C:10]([N:11]=[CH:12][N:13]4[C@@H:16]4[CH2:20][C@H:19]([NH:21][C:22](=[O:25])[CH2:23][CH3:24])[C@@H:18]([OH:26])[C@H:17]4[OH:27])=[C:9]([NH:28][CH2:29][CH:30]([C:31]4[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=4)[C:38]4[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=4)[N:8]=3)[CH2:3]2)[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1
Reactant: CCC(=O)N[C@H]1C[C@@H](n2cnc3c(NCC(c4ccc(O)cc4)c4ccc(O)cc4)nc(N4CC[C@@H](N)C4)nc32)[C@H](O)[C@@H]1O
Reactant: O=C(Cl)Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: CCC(=O)N[C@H]1C[C@@H](n2cnc3c(NCC(c4ccc(O)cc4)c4ccc(O)cc4)nc(N4CC[C@@H](NC(=O)Oc5ccccc5)C4)nc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A mixture comprising N-((1S,2R,3S,4R)-4-{2-((R)-3-amino-pyrrolidin-1-yl)-6-[2,2-bis-(4-hydroxy-phenyl)-ethylamino]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-propionamide (Example 22 step 4) (50 mg, 83 μmol) and potassium carbonate (46 mg, 332 μmol) in NMP (1 ml) is treated with phenylchloroformate and stirred at room temperature for 90 minutes. This mixture was used in the next step without purification.
Reaction SMILES: C1CCC(N=C=NC2CCCCC2)CC1.[C:16]([OH:22])(=[O:21])[CH2:17][CH2:18][CH2:19][CH3:20].[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH:44]([CH3:47])[CH2:45]O)=[C:39]([F:48])[C:38]=2[F:49])=[CH:33][CH:32]=1)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].C(OCC)(=O)C(C)O.[Li+].[BH4-]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH:44]([CH3:45])[CH2:47][O:21][C:16](=[O:22])[CH2:17][CH2:18][CH2:19][CH3:20])=[C:39]([F:48])[C:38]=2[F:49])=[CH:33][CH:32]=1)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCC(=O)O
Reactant: CCCCCCCOc1ccc(-c2ccc(OC(C)CO)c(F)c2F)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: [BH4-]
Solvent: CCOC(=O)C(C)O
Solvent: ClCCl
Product: CCCCCCCOc1ccc(-c2ccc(OC(C)COC(=O)CCCC)c(F)c2F)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
At 0° C., 0.1 mol of DCC, dissolved in methylene chloride, is added with exclusion of moisture to a mixture of 0.1 mol of pentanoic acid, 0.1 mol of optically active 2-(4'-heptyloxy-2,3-difluorobiphenyl-4-oxy)propan-1-ol (prepared by reduction of the corresponding ethyl lactate using LiBH4) and a catalytic amount of DMAP in 250 ml of methylene chloride. The mixture is subsequently stirred at room temperature for 12 hours, the precipitate is filtered off with suction, and the filtrate is worked up in a customary manner, to give optically active 4'-heptyloxy-2,3-difluoro-4-(1-valeroyloxy-2-propyloxy)biphenyl.
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C(B(CC)[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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>[N:15]1[CH:16]=[CH:17][CH:18]=[C:13]([C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)[CH:14]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: CCB(CC)c1cccnc1
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: CCOC(C)=O
Solvent: Cc1ccccc1
Product: O=Cc1ccc(-c2cccnc2)cc1
Yield: 72.3 %

Procedure:
A mixture of 4-bromobenzaldehyde (2 g, 10.8 mmol), diethyl(3-pyridyl)borane (1.75 g, 11.9 mmol), tetrakis(triphenylphosphine)palladium (375 mg, 0.32 mmol), and 2N sodium carbonate aqueous solution(10.8 ml, 21.6 mmol) in toluene (40 ml) was heated under reflux under a nitrogen atmosphere overnight. The reaction mixture was allowed to return to room temperature and diluted with ethyl acetate. The mixture was washed with water and brine, and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/1) to afford 4-(pyridin-3-yl)benzaldehyde (1.43 g, yield 72%) as a pale yellow crystalline powder.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([N+:10]([O-:12])=[O:11])[C:3]=1[O:13][CH3:14].II.[NH3:17]>O1CCCC1>[OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:17])=[C:4]([N+:10]([O-:12])=[O:11])[C:3]=1[O:13][CH3:14]
Reactant: COc1c(O)ccc(C=O)c1[N+](=O)[O-]
Reactant: N
Agent: II
Solvent: C1CCOC1
Product: COc1c(O)ccc(C#N)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.5 %

Procedure:
To a mixture of 4-hydroxy-3-methoxy-2-nitrobenzaldehyde 14.5 g (73.5 mmol) in 28% ammonia solution 150 mL and tetrahydrofuran 15 mL was added iodine 22.4 g (88.2 mmol) and stirred at room temperature for overnight. The reaction mixture was concentrated in vacuo. The residue was acidified with 2H HCl solution and extracted into diethyl ether. The organic layer was washed with brine, dried over MgSO4, filtrated and the solvent was evaporated. The residue was washed with diisopropyl ether to give the title compound 12.1 g as brown solid. Yield 84.5%
Reaction SMILES: [C:1]([O:5][O:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:21])[C:15]2C=CC=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C(C1C=CC(C(O)=O)=CC=1)(=O)CCC>>[C:1]([O:5][O:6][C:7](=[O:22])[C:8]1[CH:9]=[CH:10][C:11]([C:14](=[O:21])[CH2:15][CH2:16][CH3:17])=[CH:12][CH:13]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CC(C)(C)OOC(=O)c1ccc(C(=O)c2ccccc2)cc1
Agent: CCCC(=O)c1ccc(C(=O)O)cc1
Product: CCCC(=O)c1ccc(C(=O)OOC(C)(C)C)cc1

Procedure:
Tert-butyl-ρ-butyrylperbenzoate is prepared by the above-discussed procedure for the preparation of t-butyl-4-benzoylperbenzoate, except that the acid employed is ρ-butyryl benzoic acid and is purified by chromatography over neutral aluminum oxide with dichloromethane-ether (5:1) as eluent. The perester obtained is a yellow oil which solidifies after several months in the refrigerator.
Reaction SMILES: [H+].[H+].[Cl:3][Pt-2:4]([Cl:9])([Cl:8])([Cl:7])([Cl:6])[Cl:5].[NH3:10]>O>[NH4+:10].[NH4+:10].[Cl:3][Pt-2:4]([Cl:9])([Cl:8])([Cl:7])([Cl:6])[Cl:5]
Reactant: N
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: O
Product: [NH4+]

Procedure:
Prior to the preparation of the impregnating solution, chloroplatinic acid, H2PtCl6, was converted to the form of an ammoniacal platinum complex solution as follows: A 500 cc three-necked flask equipped with an agitater and a water cooler was charged with 100 cc of a chloroplatinic acid solution containing 10 g of Pt, and 55 cc of 9.7 N ammonia solution was added slowly to the flask to form an orange-colored precipitate of ammonium chloroplatinate. The flask was gently heated to 70° C. over the course of 30 minutes with continuous stirring, and then kept at this temperature for an additional 60 minutes to dissolve the precipitate completely. The cooled solution showed a light yellow color and had a pH of about 9.5. Finally, the concentration of platinum in the solution was adjusted to 40 g per liter of the solution.
Reaction SMILES: [H-].[Na+].[CH:3]([O:6][C:7]1[CH:16]=[CH:15][C:10]([NH:11][C:12](=[O:14])[CH3:13])=[CH:9][CH:8]=1)([CH3:5])[CH3:4].C([N-]C(C)C)(C)C.[Li+].C(NC(C)C)(C)C.C([Li])CCC.[CH2:37]([N:44]1[CH2:49][CH2:48][C:47](=[O:50])[CH2:46][CH2:45]1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O1CCCC1>[CH:3]([O:6][C:7]1[CH:16]=[CH:15][C:10]([NH:11][C:12](=[O:14])[CH2:13][C:47]2([OH:50])[CH2:48][CH2:49][N:44]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:45][CH2:46]2)=[CH:9][CH:8]=1)([CH3:5])[CH3:4]
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: CC(=O)Nc1ccc(OC(C)C)cc1
Agent: CC(C)[N-]C(C)C
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CC(C)Oc1ccc(NC(=O)CC2(O)CCN(Cc3ccccc3)CC2)cc1
Temperature: -50 °C
Reaction time: 1 h
Yield: 65.1 %

Procedure:
Sodium hydride (60% dispersion in oil; 1.99 g) was added to an anhydrous tetrahydrofuran solution (80 mL) of 4′-isopropoxyacetanilide (8.0 g) under nitrogen atmosphere while cooling with ice-water, followed by stirring at the intact temperature for 1 hour. The reaction solution was cooled to −50° C. and added with an anhydrous tetrahydrofuran solution (80 mL) of lithium diisopropylamide prepared from diisopropylamine (11.6 mL) and n-butyl lithium (1.6M hexane solution; 51.8 mL), followed by stirring at −50 to −30° C. for 1 hour. An anhydrous tetrahydrofuran solution (40 mL) of 1-benzylpiperidin-4-one (7.83 g) was added to the reaction solution above at −30° C., and the mixture was stirred −30° C. for 30 minutes, and under cooling with ice-water for 2 hours. The reaction solution was poured into ice-water, and the aqueous solution was extracted with ethyl acetate. The organic layer was sequentially washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solution was distilled off under reduced pressure. The residue obtained was purified by silica gel column chromatography (elution solvent; methylene chloride:methanol=90:10 to 75:25) to obtain the titled compound (10.3 g).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([C:17]1[N:18]=[CH:19][N:20](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:21]=1)([OH:16])[CH:13]([CH3:15])[CH3:14])[CH:6]=[CH:5]2.[CH:41](I)([CH3:43])[CH3:42]>>[CH:41]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([C:17]1[N:18]=[CH:19][NH:20][CH:21]=1)([OH:16])[CH:13]([CH3:14])[CH3:15])[CH:6]=[CH:5]2)([CH3:43])[CH3:42]
Reactant: CC(C)I
Reactant: CC(C)C(O)(c1ccc2cc(O)ccc2c1)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Product: CC(C)Oc1ccc2cc(C(O)(c3c[nH]cn3)C(C)C)ccc2c1

Procedure:
In a similar manner to that described in Example 31-(i), the reaction of 1-(6-hydroxynaphthalen-2-yl)-2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanol (0.965 g) with isopropyl iodide (0.20 ml) was carried out to give the titled compound (0.548 g) as a colorless solid.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11]3[C:12]4[CH:29]=[CH:28][N:27](S(C5C=CC(C)=CC=5)(=O)=O)[C:13]=4[N:14]=[C:15]([NH:17][C:18]4[CH:26]=[CH:25][C:21]([C:22]([NH2:24])=[O:23])=[CH:20][CH:19]=4)[N:16]=3)[CH:8]=2)[CH:3]=[N:2]1.[OH-].[K+]>O1CCOCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11]3[C:12]4[CH:29]=[CH:28][NH:27][C:13]=4[N:14]=[C:15]([NH:17][C:18]4[CH:19]=[CH:20][C:21]([C:22]([NH2:24])=[O:23])=[CH:25][CH:26]=4)[N:16]=3)[CH:8]=2)[CH:3]=[N:2]1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(Nc4ccc5cn[nH]c5c4)nc(Nc4ccc(C(N)=O)cc4)nc32)cc1
Agent: [K+]
Agent: [OH-]
Solvent: C1COCCO1
Product: NC(=O)c1ccc(Nc2nc(Nc3ccc4cn[nH]c4c3)c3cc[nH]c3n2)cc1
Temperature: 70 °C
Yield: 22.4 %

Procedure:
To a solution of 4-(4-(1H-indazol-6-ylamino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)benzamide (50 mg, 0.093 mmol) in dioxane (3 mL), aq. 1N KOH (1.50 mL, 1.50 mmol) was added. The mixture was heated at 70° C. for 4 h. before it was concentrated in vacuo. The residue was then acidified with acetic acid (HOAc) (2.0 mL) and purified by HPLC to give the title compound (8 mg). MS 385.2 (M+H) (Compound 12-1).
Reaction SMILES: [BH4-].[Na+].[C:3]([O:7][C:8](=[O:26])[NH:9][CH:10]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[CH:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1)([CH3:6])([CH3:5])[CH3:4]>CO.C1COCC1>[C:3]([O:7][C:8](=[O:26])[NH:9][CH:10]([CH:11]1[CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]1)[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)([CH3:6])([CH3:4])[CH3:5]
Reactant: COc1ccc(C(NC(=O)OC(C)(C)C)C2CCC(=O)CC2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(C(NC(=O)OC(C)(C)C)C2CCC(O)CC2)cc1
Reaction time: 7 h

Procedure:
Sodium borohydride (12 mg, 0.34 mmol) and 2 drops methanol were added to a solution of [(4-methoxy-phenyl)-(4-oxo-cyclohexyl)-methyl]-carbamic acid tert-butyl ester (33, 110 mg) in THF (5 mL). After stirring for 7 hours the reaction was worked up by washing the solution with saturated sodium bicarbonate solution and brine. After drying the organic phase over sodium sulphate, followed by filtration, evaporation gave 101 mg of the desired cis/trans isomer mixture (34) as a colourless solid, which was used directly in the next stage. Rt=1.36, 1.39 min (Method 5). Detected mass: 219.2 (M—C4H8—CO2—H2O+).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]#[N:17].[CH3:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([CH3:27])=[C:24]([CH:26]=1)[NH2:25].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCCO)C>[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:25][C:24]3[CH:26]=[C:20]([O:19][CH3:18])[CH:21]=[CH:22][C:23]=3[CH3:27])=[C:3]([C:16]#[N:17])[CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]
Reactant: N#Cc1cnc2cc(Cl)c([N+](=O)[O-])cc2c1Cl
Reactant: COc1ccc(C)c(N)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCCO
Solvent: c1ccncc1
Product: COc1ccc(C)c(Nc2c(C#N)cnc3cc(Cl)c([N+](=O)[O-])cc23)c1
Temperature: 115 °C
Yield: 62.1 %

Procedure:
A mixture of 0.9 g (3.36 mmol) of 4,7-dichloro-6-nitro-3-quinolinecarbonitrile, 0.55 g (4.0 mmol) of 5-methoxy-2-methylaniline, 0.46 g (4.0 mmol) of pyridine hydrochloride in 10.0 mL of 2-ethoxyethanol is heated at 115° C. for 1 hour, cooled and poured into a saturated solution of sodium bicarbonate. The oil is extracted with methylene chloride, dried over anhydrous sodium sulfate and the solvent is evaporated to yield a foam. This is purified by silica gel chromatography, eluting with methylene chloride/methanol (99.5:0.5) to yield 0.77 g of 7-chloro-4-(5-methoxy-2-methylanilino)-6-nitro-3-quinolinecarbonitrile as a yellow solid, mp 180–182° C.