Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:14]([OH:17])[CH2:15][CH3:16])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OCC)C.[Cr](O)(O)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>O>[O:1]([C:8]1[CH:9]=[C:10]([C:14](=[O:17])[CH2:15][CH3:16])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCC(O)c1cccc(Oc2ccccc2)c1
Agent: O=[Cr](=O)(O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Product: CCC(=O)c1cccc(Oc2ccccc2)c1
Reaction time: 2 h

Procedure:
A solution of 35 g of 1-(3-phenoxyphenyl)propan-1-ol and 50 ml of ethyl ether is treated with 1.1 equivalants of chromic acid, which is added dropwise over a 30 minute period. The reaction mixture is allowed to warm to 20°-25° C. and stirred for about 2 hours. Then the reaction mixture is added to a mixture of 25 ml of ethyl ether and 50 ml of water, and sodium carbonate is slowly added to neutralize the acid. The phases are separated and the aqueous phase is reextracted twice with ethyl ether. The ethereal extracts are combined and evaporated under reduced pressure to yield 1-(3-phenoxyphenyl)-propan-1-one as an oil.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[O:19]([CH2:27][CH:28]([CH3:55])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[C:41]([S:42]([NH:45][C:46]3[C:51]([O:52][CH3:53])=[N:50][C:49]([CH3:54])=[CH:48][N:47]=3)(=[O:44])=[O:43])=[CH:40][CH:39]=[CH:38][N:37]=2)=[CH:32][CH:31]=1)[Si](C(C)(C)C)(C)C>C1COCC1.O>[OH:19][CH2:27][CH:28]([CH3:55])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[C:41]([S:42]([NH:45][C:46]3[C:51]([O:52][CH3:53])=[N:50][C:49]([CH3:54])=[CH:48][N:47]=3)(=[O:44])=[O:43])=[CH:40][CH:39]=[CH:38][N:37]=2)=[CH:32][CH:31]=1
Reactant: COc1nc(C)cnc1NS(=O)(=O)c1cccnc1-c1ccc(CC(C)CO[Si](C)(C)C(C)(C)C)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: COc1nc(C)cnc1NS(=O)(=O)c1cccnc1-c1ccc(CC(C)CO)cc1
Reaction time: 0.75 h
Yield: 80.5 %

Procedure:
Tetrabutylammonium fluoride (0.4 ml of a 1.0 M solution in THF) was added to a solution of 2-[4-(2-((tert-butyldimethylsiloxy)methyl)propyl)phenyl]-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (118 mg) in THF (5 ml) at ambient temperature. More tetrabutylammonium fluoride solution was added after 0.25 hour (0.4 ml), after 0.75 hour (1.0 ml) and finally after 1.5 hours (0.2 ml). The reaction mixture was stirred for a further 0.5 hour, diluted with water (10 ml) and the reaction mixture was extracted with dichloromethane (4×10 ml). The combined organic extracts were dried over MgSO4 and evaporated to give an amber oil. This was purified by gradient elution with 0-50% methanol/dichloromethane through a silica gel Mega Bond Elut column to give 2-[4-(3-hydroxy-2-methylpropyl)phenyl]-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (75 mg) as a white crystalline solid, m.p. 118-119° C.; 1H NMR (DMSO-d6): 0.95 (d, 3H), 1.35 (m, 1H), 2.0 (m, 1H), 2.3 (s, 3H), 2.5 (m, 1H), 2.9 (m, 1H), 3.5 (m, 2H), 3.8 (s, 3H), 6.65 (s, 1H), 7.2 (m, 4H), 7.35 (s, 1H), 7.5 (m, 1H), 8.7 (d, 1H), 8.8 (dd, 1H); mass spectrum (+ve ESP): 429 (M+H)+.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:7])=[O:6].[CH:14]([NH2:17])([CH3:16])[CH3:15]>>[ClH:1].[CH3:15][CH:14]([NH:17][CH2:2][CH2:3][CH2:4][S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:7])=[O:6])[CH3:16]
Reactant: CC(C)N
Reactant: O=S(=O)(CCCCl)c1ccccc1
Product: CC(C)NCCCS(=O)(=O)c1ccccc1
Product: Cl

Procedure:
A solution of 66.55 g (0.3052 mole) of 3-chloropropylphenyl sulfone (prepared by reacting m-chloroperoxybenzoic acid and 3-chloropropyl phenylsulfide in methylene chloride) in 200 ml of isopropylamine was heated at 100° C. overnight in a bomb. The isopropylamine was removed by rotary evaporation and the residue partitioned between chloroform and water. The chloroform layer was extracted with 1N sulfuric acid. The acidic layer was made alkaline and extracted with chloroform. The combined chloroform extract was evaporated to give an oil, the free base of the title compound. The oil was converted to the hydrochloride salt by reacting with ethereal hydrogen chloride. Recrystallization of the precipitated salt from methanol-diethyl ether gave 48.04 g (65.3%) of white crystalline powder, m.p. 185°-186° C.
Reaction SMILES: [CH2:1]([N:3]([CH2:42][CH3:43])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:36]3C=CC=C[CH:37]=3)[O:15][C:14]3[C:16]4[C:21]([C:22](OS(C(F)(F)F)(=O)=O)=[C:23]([C:24]([O:26][CH3:27])=[O:25])[C:13]=3[CH:12]=[CH:11]2)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:6][CH:5]=1)[CH3:2].[CH2:44]([C:49]1[CH:54]=[CH:53][C:52]([C:55]2[CH:60]=[CH:59][C:58](B(O)O)=[CH:57][CH:56]=2)=[CH:51][CH:50]=1)[CH2:45][CH2:46][CH2:47][CH3:48].C([O-])([O-])=O.[K+].[K+].[C:70]1(C)[CH:75]=CC=[CH:72][CH:71]=1>C(O)C>[CH2:1]([N:3]([CH2:42][CH3:43])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:36]3[CH:37]=[CH:72][CH:71]=[CH:70][CH:75]=3)[O:15][C:14]3[C:16]4[C:21]([C:22]([C:58]5[CH:59]=[CH:60][C:55]([C:52]6[CH:53]=[CH:54][C:49]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])=[CH:50][CH:51]=6)=[CH:56][CH:57]=5)=[C:23]([C:24]([O:26][CH3:27])=[O:25])[C:13]=3[CH:12]=[CH:11]2)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:6][CH:5]=1)[CH3:2]
Reactant: CCCCCc1ccc(-c2ccc(B(O)O)cc2)cc1
Reactant: CCN(CC)c1ccc(C2(c3ccccc3)C=Cc3c(C(=O)OC)c(OS(=O)(=O)C(F)(F)F)c4ccccc4c3O2)cc1
Reactant: Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCCCCc1ccc(-c2ccc(-c3c(C(=O)OC)c4c(c5ccccc35)OC(c3ccccc3)(c3ccc(N(CC)CC)cc3)C=C4)cc2)cc1
Yield: 30 %

Procedure:
A solution containing methyl 2-(4-diethylamino-phenyl)-2-phenyl-6-trifluoromethanesulfonyloxy-2H-naphtho[1,2-b]pyran-5-carboxylate (0.90 g, 1.47 mmol), 4′-pentyl-4-biphenylboronic acid (0.39 g. 1.47 mmol), K2CO3 (0.30 g), PhMe (30 mL), ethanol (30 mL) and degassed for 1 h. Pd(PPh3)4 (0.085 g, 5% mol) was added and the reaction mixture was heated at reflux for 16 hrs. The reaction mixture was poured into water (100 mL), extracted with DCM (4×50 mL), dried (MgSO4) and the solvent removed under reduced pressure. The residue was chromatographed on silica using DCM (20% hexanes) and recrystallised from acetone-MeOH to give a pale blue powder (2.3 g, 30%) mp: 177-178° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[CH2:11][C@H:10]([N:22]([CH2:39][CH:40]([CH3:42])[CH3:41])[C:23]([C:25]2[N:29]([CH2:30][CH2:31][C:32]([OH:34])=O)[C:28]3[CH:35]=[CH:36][CH:37]=[CH:38][C:27]=3[N:26]=2)=[O:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH4+].[N:44]1(O)C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[NH2:44][C:32](=[O:34])[CH2:31][CH2:30][N:29]1[C:28]2[CH:35]=[CH:36][CH:37]=[CH:38][C:27]=2[N:26]=[C:25]1[C:23]([N:22]([CH2:39][CH:40]([CH3:41])[CH3:42])[C@H:10]1[CH2:11][C@@H:12]([C:14]([N:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)=[O:15])[CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1)=[O:24]
Reactant: CC(C)CN(C(=O)c1nc2ccccc2n1CCC(=O)O)[C@H]1C[C@@H](C(=O)N2CCOCC2)CN(C(=O)OC(C)(C)C)C1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CC(C)CN(C(=O)c1nc2ccccc2n1CCC(N)=O)[C@H]1C[C@@H](C(=O)N2CCOCC2)CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 15 h
Yield: 92.7 %

Procedure:
3-(2-{[(3S, 5R)-1-(tert-Butoxycarbonyl)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl](2-methylpropyl)carbamoyl}-1H-benzimidazol-1-yl)propanoic acid (215 mg) and 1H-1,2,3-benzotriazol-1-ol ammonium salt (84 mg) were dissolved in DMF (5 ml), WSC.HCl (142 mg) was added and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with 10% aqueous citric acid solution and extracted with ethyl acetate. The extract was washed with aqueous sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (199 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C:9]2=[O:13])[CH:5]=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]([OH:22])=[O:21])=[CH:16][CH:15]=1.IC.[C:25](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C:9]2=[O:13])[CH:5]=[CH:4][C:3]=1[C:14]1[CH:15]=[CH:16][C:17]([C:20]([O:22][CH3:25])=[O:21])=[CH:18][CH:19]=1
Reactant: Cc1cc(N2CCCC2=O)ccc1-c1ccc(C(=O)O)cc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(-c2ccc(N3CCCC3=O)cc2C)cc1

Procedure:
The title compound was prepared from 2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carboxylic acid (D13) by stirring a DMF solution together with iodomethane and potassium carbonate for 3 hours, followed by dilution with water and extraction into ethyl acetate.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1.C(N(CC)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[O:40]=[C:41]1[CH2:46][S:45][C:44]2[CH:47]=[CH:48][C:49]([C:51](O)=[O:52])=[N:50][C:43]=2[NH:42]1>CN(C=O)C>[CH3:1][N:2]([CH2:3][CH:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1)[C:51]([C:49]1[CH:48]=[CH:47][C:44]2[S:45][CH2:46][C:41](=[O:40])[NH:42][C:43]=2[N:50]=1)=[O:52]
Reactant: O=C1CSc2ccc(C(=O)O)nc2N1
Reactant: CNCC1CCN(C(=O)OC(C)(C)C)C1
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(CC1CCN(C(=O)OC(C)(C)C)C1)C(=O)c1ccc2c(n1)NC(=O)CS2
Temperature: 25 °C
Reaction time: 24 h
Yield: 82.7 %

Procedure:
To a solution of 1,1-dimethylethyl 3-[(methylamino)methyl]-1-pyrrolidinecarboxylate (153 mg, 0714 mmol) in DMF (2 mL) were added triethylamine (0.1 mL, 0.714 mmol) followed by DPPA (0.154 mL, 0.714 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxylic acid (150 mg, 0.714 mmol). After stirring at room temperature for 24 h, the solution was partitioned between ethyl acetate and K CO solution (5% in H O). The aqueous layer was extracted several times with ethyl acetate. The organic fractions were combined, dried over MgSO, concentrated and purified with column chromatography (silica, 0-5% MeOH in DCM) to provide the title compound as an off-white solid (240 mg, 83%): LC/MS (ES) m/e 407 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C(O[N:24]1N=N[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.NC1C=CC=CC=1.C(N(C(C)C)CC)(C)C>C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4]([NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:6]
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: COc1cc(C(=O)O)c(Cl)cc1[N+](=O)[O-]
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: Nc1ccccc1
Solvent: CC#N
Product: COc1cc(C(=O)Nc2ccccc2)c(Cl)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 69 %

Procedure:
To a solution of 2-chloro-5-methoxy-4-nitro-benzoic acid (200 mg, 0.86 mmol) in acetonitrile (10 mL) was added HBTU (327 mg, 0.86 mmol) followed by aniline (0.08 mL, 0.86 mmol) and diisopropylethylamine (0.56 mL, 3.20 mmol) and the resulting mixture was stirred at room temperature overnight. The reaction mixture was then heated at 60° C. for 24 hours and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (50 mL) and water (50 mL); the organic layer was separated and washed with water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (hexane/EtOAc, 75/25) to give 182 mg of 2-chloro-5-methoxy-4-nitro-N-phenyl-benzamide as a light yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:34](=[CH:35][CH:36]=3)[CH2:33][C@:23]3([C:31]5[C:26](=[N:27][CH:28]=[CH:29][CH:30]=5)[NH:25][C:24]3=[O:32])[CH2:22]4)=[O:17])[C:13](=[O:37])[C:12]([CH3:39])([CH3:38])[CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[OH:40]OS([O-])=O.[K+].O>CO>[F:8][C:6]1[CH:5]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:34](=[CH:35][CH:36]=3)[CH2:33][C@:23]3([C:31]5[C:26](=[N+:27]([O-:40])[CH:28]=[CH:29][CH:30]=5)[NH:25][C:24]3=[O:32])[CH2:22]4)=[O:17])[C:13](=[O:37])[C:12]([CH3:39])([CH3:38])[CH2:11][CH2:10]2)[CH:3]=[C:2]([F:1])[CH:7]=1
Reactant: CC1(C)CC[C@@H](c2cc(F)cc(F)c2)N(CC(=O)Nc2ccc3c(c2)C[C@@]2(C3)C(=O)Nc3ncccc32)C1=O
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: CO
Solvent: O
Product: CC1(C)CC[C@@H](c2cc(F)cc(F)c2)N(CC(=O)Nc2ccc3c(c2)C[C@@]2(C3)C(=O)Nc3c2ccc[n+]3[O-])C1=O

Procedure:
A mixture of 2-[(6S)-6-(3,5-difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-[(2R)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-5-yl]acetamide (20.0 mg, 0.038 mmol, described in Example 49) and Oxone® (70.0 mg, 0.113 mmol) in MeOH (0.5 mL) and water (0.5 mL) was stirred at ambient temperature for 3 h. The reaction mixture was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. Lyophilization provided the title compound. MS: m/z=547 (M+1). HRMS: m/z=547.2155; calculated m/z=547.2152 for C30H29F2N4O4.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:13]([CH3:15])=[CH2:14])[CH:9]=2)[CH:4]=1.[Se](=O)=[O:17]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13](=[CH2:15])[CH2:14][OH:17])[CH:7]=[CH:6]2
Reactant: O=[Se]=O
Reactant: C=C(C)c1ccc2cc(OC)ccc2c1
Solvent: ClCCl
Product: C=C(CO)c1ccc2cc(OC)ccc2c1

Procedure:
A solution of 0.20 g 2-methoxy-6-isopropenylnaphthalene and 0.12 g selenium dioxide (SeO2) in 10 ml methylene chloride was heated at reflux for 22 hours. The cooled solution was then washed with 10 ml 20% (by weight) sodium hydroxide (NaOH) after adding 40 ml ethylene dichloride (EDC). The organic layer was dried over MgSO4, filtered, and concentrated to give an oil which was purified on a 2×17 cm silica (SiO2) column using a 5 to 1 by volume solution of heptane and ethyl acetate. The product containing fractions were combined and concentrated to give 2-(6-methoxy-2-naphthyl)prop-2-en-1-ol.
Reaction SMILES: [C:1]([N:4]1[C:16]2[CH:15]=[CH:14][C:13](I)=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[C:8](I)[CH:9]=2)(=[O:3])[CH3:2].[C:19]1([SiH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN1CCCC1=O>[C:1]([N:4]1[C:16]2[CH:15]=[CH:14][C:13]([Si:25]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[C:8]([Si:25]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH:9]=2)(=[O:3])[CH3:2]
Reactant: c1ccc([SiH](c2ccccc2)c2ccccc2)cc1
Reactant: CC(=O)n1c2ccc(I)cc2c2cc(I)ccc21
Solvent: CN1CCCC1=O
Product: CC(=O)n1c2ccc([Si](c3ccccc3)(c3ccccc3)c3ccccc3)cc2c2cc([Si](c3ccccc3)(c3ccccc3)c3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 19 h
Yield: 12.5 %

Procedure:
9-Acetyl-3,6-diiodocarbazole (10.0 g) and triphenylsilane (12.4 g) were dry N-methylpyrrolidone (200 mL), followed by bubbling with argon gas for 30 min. Tripotassium phosphate (27.6 g) and bis(tri-t-butylphosphine)palladium (0.111 g) were added thereto, and the mixture was stirred at room temperature for 19 hours. The obtained reaction mixture was filtrated, and the filtrate was extracted with methylene chloride. The separated organic layer was washed with brine and dried, and the methylene chloride was evaporated. The residue was treated through silica gel column chromatography (eluent: toluene), to thereby obtain 1.97 g of 9-acetyl-3,6-bis(triphenylsilyl)carbazole as colorless powder.
Reaction SMILES: [CH3:1][C:2]([CH2:4][OH:5])=[O:3].[CH3:6][C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[CH2:8]>>[C:9]1([CH:7]([CH3:8])[CH3:6])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH3:1][C:2]([CH:4]=[O:5])=[O:3]
Reactant: C=C(C)c1ccccc1
Reactant: CC(=O)CO
Product: CC(=O)C=O
Product: CC(C)c1ccccc1

Procedure:
so that the catalyst causes a reaction between the impurity acetol and alpha-methyl styrene to form cumene and pyruvic aldehyde, then
Reaction SMILES: Cl[C:2]([C:4]1[CH:34]=[CH:33][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17](=[O:32])[CH2:18][NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1)=[O:3].[CH3:35][O:36][CH2:37][CH2:38][NH2:39].ClCCl.O>CO>[CH3:35][O:36][CH2:37][CH2:38][NH:39][C:2]([C:4]1[CH:34]=[CH:33][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17](=[O:32])[CH2:18][NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1)=[O:3]
Reactant: O=C(CNC(=O)c1cccc(C(F)(F)F)c1)NCC1CCN(Cc2ccc(C(=O)Cl)cc2)CC1
Reactant: COCCN
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: COCCNC(=O)c1ccc(CN2CCC(CNC(=O)CNC(=O)c3cccc(C(F)(F)F)c3)CC2)cc1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
A mixture of 1-[4-(chloroformyl)benzyl]-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (0.042 mmol), 2-methoxyethylamine (3.8 mg, 0.050 mmol), piperidinomethylpolystyrene (46 mg) and dichloromethane (1.5 mL) was stirred at room temperature for 17 h. Water (0.020 mL) was added and the mixture was stirred for 30 min. Methanol (1 mL) was added and the mixture was loaded onto Varian™ SCX column, and washed with CH3OH (10 mL). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated to afford 1-[4-{N-(2-methoxyethyl)carbamoyl}benzyl]-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (Compound No. 1612) (26.7 mg, 100%): The purity was determined by RPLC/MS (92%); ESI/MS m/e 535.2 (M−+H, C27H33F3N4O4).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH2:15][C:16]2[O:20][CH:19]=[C:18]([C:21](O)=[O:22])[CH:17]=2)[CH3:14])(=[O:12])=[O:11])=[C:5]([CH3:24])[CH:4]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH3:56][NH:57][CH2:58][C:59]1[CH:70]=[CH:69][C:62]([CH2:63][N:64]2[CH2:67][CH:66]([OH:68])[CH2:65]2)=[CH:61][CH:60]=1>C(Cl)Cl>[OH:68][CH:66]1[CH2:65][N:64]([CH2:63][C:62]2[CH:69]=[CH:70][C:59]([CH2:58][N:57]([CH3:56])[C:21]([C:18]3[CH:17]=[C:16]([CH2:15][N:13]([S:10]([C:6]4[C:7]([CH3:9])=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[CH3:24])(=[O:11])=[O:12])[CH3:14])[O:20][CH:19]=3)=[O:22])=[CH:60][CH:61]=2)[CH2:67]1
Reactant: CNCc1ccc(CN2CC(O)C2)cc1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)O)co2)c(C)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)N(C)Cc3ccc(CN4CC(O)C4)cc3)co2)c(C)c1

Procedure:
The title compound was prepared according to general procedure BH using 5-{[(4-methoxy-2,6-dimethyl-benzenesulfonyl)-methyl-amino]-methyl}-furan-3-carboxylic acid (35 mg, 0.10 mmol), EDCI (27 mg, 0.14 mmol), HOBt (20 mg, 0.15 mmol), DIPEA (0.04 mL, 0.20 mmol), 1-(4-methylaminomethyl-benzyl)-azetidin-3-ol hydrochloride (29 mg, 0.11 mmol) and DCM (10 mL).
Reaction SMILES: [C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:23][CH2:24][C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31]C)=[O:30])=[CH:27][CH:26]=2)=[N:10][C:11]([C:17]2[CH:18]=[N:19][CH:20]=[N:21][CH:22]=2)=[N:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[OH-]>CO.C1COCC1.O>[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:29]([OH:31])=[O:30])=[CH:33][CH:34]=2)=[N:10][C:11]([C:17]2[CH:18]=[N:19][CH:20]=[N:21][CH:22]=2)=[N:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1ccc(CNc2nc(-c3cncnc3)nc3cccc(-c4ccccc4)c23)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: O=C(O)c1ccc(CNc2nc(-c3cncnc3)nc3cccc(-c4ccccc4)c23)cc1
Temperature: 45 °C
Reaction time: 12 h
Yield: 64.8 %

Procedure:
To a solution of methyl 4-((5-phenyl-2-(pyrimidin-5-yl)quinazolin-4-ylamino)methyl)benzoate (400 mg, 0.89 mmol) in MeOH-THF—H2O (6 mL-6 mL-0.5 mL) was added LiOH (112 mg, 2.67 mmol). Upon completion of addition, the reaction mixture was heated to 45° C. where it stirred for 12 h. After this time, the reaction mixture was concentrated under reduced pressure to remove the MeOH and THF and then carefully acidified with 1.5N HCl. The resulting precipitate was collected by filtration to afford 4-((5-phenyl-2-(pyrimidin-5-yl)quinazolin-4-ylamino)methyl)benzoic acid (250 mg) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.87 (bs, 1H), 9.68 (s, 2H), 9.39 (s, 1H), 8.09 (m, 1H), 7.98 (t, J=8.0 Hz, 1H), 7.86 (d, J=8.0 Hz, 2H), 7.53-7.48 (m, 6H), 7.26 (d, J=8.0 Hz, 2H), 6.65 (bs, 1H), 4.78 (d, J=5.2 Hz, 2H). LCMS Method O: retention time 1.73 min, [M+1]=434.2. HPLC Method B: purity 98.1%, retention time 8.24 min.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][CH:3]=1.CN(C=O)C.C([N:23]=[C:24]=[S:25])(=O)C1C=CC=CC=1>C(Cl)Cl>[OH:9][CH2:8][C:6]1[N:7]=[C:2]([NH:1][C:24]([NH2:23])=[S:25])[CH:3]=[CH:4][CH:5]=1
Reactant: Nc1cccc(CO)n1
Reactant: O=C(N=C=S)c1ccccc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: NC(=S)Nc1cccc(CO)n1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
(6-Amino-pyridin-2-yl)-methanol (6-2, 1.00 g, 8.06 mmol) was dissolved in 20 mL anhydrous CH2Cl2 and 5 mL anhydrous DMF under N2. Benzoylisothiocyanate (1.19 mL, 8.86 mmol) was added and the reaction was stirred at room temperature fro 16 h. The reaction was concentrated in vacuo and to the resulting residue was added 24 mL 1M NaOH (aq) and 24 mL THF. The resulting mixture was heated to reflux for 3 h. The THF was removed in vacuo and a white precipitate formed. The mixture was filtered and washed with water to provide the titled compound as a white solid. 1H NMR(DMSO-d6): δ 10.58 (bs, 1H), 10.48 (bs, 1H), 8.84 (bs, 1H), 7.74 (t, 1H, J=8.1 Hz), 7.06 (d, 1H, J=7.5 Hz), 7.01 (d, 1H, J=8.1 Hz), 5.47 (t, 1H, J=5.9 Hz), 4.47 (d, 2H, J=5.7 Hz).
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([OH:12])[C:9]([O:13][CH3:14])=[CH:8][C:7]=1[CH3:15])=[O:5].FC(F)(F)S(O)(=O)=O.[CH3:29][C:30]([CH3:32])=[CH2:31].[OH-].[Na+]>C(Cl)Cl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([O:12][C:30]([CH3:32])([CH3:31])[CH3:29])[C:9]([O:13][CH3:14])=[CH:8][C:7]=1[CH3:15])=[O:5]
Reactant: C=C(C)C
Reactant: COc1cc(C)c(C(=O)c2c(Cl)cccc2Cl)cc1O
Agent: O=S(=O)(O)C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(C)c(C(=O)c2c(Cl)cccc2Cl)cc1OC(C)(C)C

Procedure:
A solution of 2,6-dichloro-5'-hydroxy-4'-methoxy-2'-methyl-benzophenone (3.0 g; 9.6 mmol) in 50 ml of methylenechloride is cooled down to -70° C., trifluoromethanesulfonic acid (0.3 ml) is added, then a stream of 2-methylpropene (5.5 g; 100 mmol) is introduced within 4 hours. Triethylamine (1.2 ml) is added, the temperature goes up to 20° C. The solution is shaken twice with diluted sodium hydroxide and the solvent is evaporated. The residue is purified chromatographically (flash column with 30 g of silicagel, elution with toluene/acetone 20:1 (v/v)). The residue is treated with petrolether to give 0.7 g of white crystalls (20% y); mp. 102° C.