Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:6]([N:8]([CH2:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([C:17]#[C:18][CH2:19][O:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH2:13][CH2:12]1)C)=O)(C)(C)C.[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28]>C(Cl)Cl>[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28].[CH3:6][NH:8][CH2:10][C@H:11]1[CH2:12][CH2:13][C@H:14]([C:17]#[C:18][CH2:19][O:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH2:15][CH2:16]1
Reactant: CN(C[C@H]1CC[C@H](C#CCOS(C)(=O)=O)CC1)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CNC[C@H]1CC[C@H](C#CCOS(C)(=O)=O)CC1
Reaction time: 0.25 h

Procedure:
A solution of 12.5 g (corresponds to 28.9 mmol) of crude trans-methanesulfonic acid 3-{4-[(tert-butoxycarbonyl-methyl-amino)-methyl]-cyclohexyl}-prop-2-ynyl ester in 160 ml methylenechloride was treated at 0° C. with 78 ml of trifluoroacetic acid (for 30 minutes). After 15 minutes at this temperature, the reaction was evaporated, redissolved in toluene and evaporated (4×) to give 23.12 g of crude trans-methanesulfonic acid 3-(4-methylaminomethyl-cyclohexyl)-prop-2-ynyl ester trifluoro-acetate as dark brown viscous oil, MS: 260 (MH+).
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH:21]([C:24]1[N:25]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:26](=[O:37])[C:27]2[C:32]([C:33]([F:36])([F:35])[F:34])=[N:31][O:30][C:28]=2[N:29]=1)[CH2:22][CH3:23])[C:12](=[O:20])[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH:21]([C:24]1[N:25]([CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:26](=[O:37])[C:27]2[C:32]([C:33]([F:36])([F:35])[F:34])=[N:31][O:30][C:28]=2[N:29]=1)[CH2:22][CH3:23])[C:12](=[O:20])[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1
Reactant: CCC(c1nc2onc(C(F)(F)F)c2c(=O)n1Cc1ccccc1)N(CCCNC(=O)OC(C)(C)C)C(=O)c1ccc(C)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCC(c1nc2onc(C(F)(F)F)c2c(=O)n1Cc1ccccc1)N(CCCN)C(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 95.9 %

Procedure:
To a solution of 12 (52 mg, 0.083 mmol) in CH2Cl2 (4.0 mL) stirred at room temperature was added TFA (1.0 mL). The reaction mixture was stirred at room temperature for 30 min. Solvent was removed in vacuo, the residue was purified by preparative HPLC to give 13 as a white solid (42 mg, 96%). MS (ESI): 528 (M+H)+.
Reaction SMILES: Br[C:2]1[C:3]2[C:4]3[CH:17]=[CH:16][S:15][C:5]=3[C:6](=[O:14])[NH:7][C:8]=2[CH:9]=[CH:10][C:11]=1[O:12][CH3:13].CC1(C)C(C)(C)OB([C:26]2[CH:31]=[CH:30][C:29]([C@@H:32]([CH3:42])[CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:28][CH:27]=2)O1>>[CH3:13][O:12][C:11]1[CH:10]=[CH:9][C:8]2[NH:7][C:6](=[O:14])[C:5]3[S:15][CH:16]=[CH:17][C:4]=3[C:3]=2[C:2]=1[C:26]1[CH:27]=[CH:28][C:29]([C@@H:32]([CH3:42])[CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[CH:30][CH:31]=1
Reactant: C[C@@H](CNC(=O)OC(C)(C)C)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Reactant: COc1ccc2[nH]c(=O)c3sccc3c2c1Br
Product: COc1ccc2[nH]c(=O)c3sccc3c2c1-c1ccc([C@@H](C)CNC(=O)OC(C)(C)C)cc1
Yield: 68.5 %

Procedure:
Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.5 g, 4.4 mmol) was reacted with (R)-tert-butyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propylcarbamate (2.0 g, 6.4 mmol) to afford the desired product (1.4 g, 48%) as a brown solid: ESI MS m/z 465 [C26H28N2O4S+H]+.
Reaction SMILES: [C:1]([CH2:9][C:10]([O:12][CH3:13])=[O:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[Na].[CH2:15](Br)[CH:16]=[CH2:17]>CO>[CH3:13][O:12][C:10](=[O:11])[CH:9]([C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1)[CH2:17][CH:16]=[CH2:15]
Reactant: COC(=O)CC(=O)c1cccnc1
Reactant: C=CCBr
Agent: [Na]
Solvent: CO
Product: C=CCC(C(=O)OC)C(=O)c1cccnc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Methyl 2-(nicotinoyl)acetate (17.9 g, prepared by the method of E. Wenkert el al. J. Org. Chem., 1983, 48, 5006) was added under argon to a solution of sodium metal (2.3 g) in methanol (200 ml) and the resulting mixture was stirred at 25° C. for 30 mins. Allyl bromide (12.0 g) was then added and stirring was continued overnight. A further amount (about 2 g) of allyl bromide was added, the mixture was stirred for 48 hours, and then concentrated. The residual oil was partitioned between water and ether and the aqueous layer was extracted three times with ether. The combined extracts were washed with saturated brine, dried (MgSO4) and concentrated. The residue was purified by flash column chromatography, eluting with a mixture of petroleum ether (b.p. 60°-80°) and ethyl acetate (1:1, v/v) to give methyl-2-nicotinoyl-4-pentenoate (A) as a pale yellow oil (13.8 g); NMR 2.6-2.9 (2H,m), 3.7 (3H,s), 4.4 (1H,m), 4.9-5.2 (2H,m), 5.5-6.0 (1H,m), 7.2-7.5 (1H,m), 8.1-8.3 (1H,m), 8.7-8.8 (1H,m) and 9.1-9.2 (1H,m).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[OH:11].[CH2:12](O)[CH:13]1[O:17][CH2:16][CH2:15][CH2:14]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH2:12][CH:13]1[CH2:14][CH2:15][CH2:16][O:17]1
Reactant: OCC1CCCO1
Reactant: O=[N+]([O-])c1ccc(Cl)c(O)c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(Cl)c(OCC2CCCO2)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 2-chloro-5-nitrophenol (3.39 g, 19.52 mmol), tetrahydrofurfuryl alcohol (1.99 g, 19.52 mmol), and Ph3P (5.12 g, 19.52 mmol) in 34 ml THF, cooled to −15° C., was added dropwise, over 90 min, a solution of DIAD (4.15 g, 20.5 mmol). The reaction was warmed to RT and stirred for 18 h. The reaction was concentrated to dryness. The crude residue was treated with a small mix of Et2O and hexanes and sonicated so as to triturate out bulk of impurities, which were filtered off. The filtrate was concentrated to dryness. The resulting residue was purified by silica gel column chromatography using EtOAc in hexanes to elute the title compound.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.[NH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]([N:39]1[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]1)=[O:38]>>[CH3:29][O:28][C:14]1[CH:15]=[C:16]([CH:26]=[CH:27][C:13]=1[NH:12][C:4]1[N:3]=[C:2]([NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[C:37]([N:39]2[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]2)=[O:38])[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=1)[CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21]
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Cl)n2)c(OC)c1)OCC
Reactant: CN1CCN(C(=O)c2ccccc2N)CC1
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccccc3C(=O)N3CCN(C)CC3)n2)c(OC)c1)OCC

Procedure:
The title product was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate and the commercially available (2-aminophenyl)-(4-methylpiperazin-1-yl)-methanone. MS (ES+): m/z 637.40 (100) [MH+]; HPLC: tR=0.69 min (UPLC, purity).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[N:14]=[CH:15][NH:16][CH:17]=3)=[C:11]([CH2:18][O:19][CH3:20])[O:10][N:9]=2)=[CH:4][CH:3]=1.F[C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[N:14]=[CH:15][N:16]([C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=4)[CH:17]=3)=[C:11]([CH2:18][O:19][CH3:20])[O:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: COCc1onc(-c2ccc(F)cc2)c1-c1c[nH]cn1
Reactant: Fc1ccc(C(F)(F)F)cc1
Product: COCc1onc(-c2ccc(F)cc2)c1-c1cn(-c2ccc(C(F)(F)F)cc2)cn1
Yield: 57 %

Procedure:
As described for Example 142f, 3-(4-fluoro-phenyl)-4-(1H-imidazol-4-yl)-5-methoxymethyl-isoxazole (546 mg, 2.0 mmol) was converted, using 1-fluoro-4-trifluoromethylbenzene instead of 1-(4-fluorophenyl)-ethanone, to the title compound (520 mg, 57%) which was obtained as light yellow solid. MS: m/e=418.4[M+H]+.
Reaction SMILES: [C:1]([N:3]=[C:4]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)OC)#[N:2].[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([CH2:18][CH2:19][NH2:20])=[CH:16][CH:15]=1>CO>[C:1]([NH:3][C:4]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)=[N:20][CH2:19][CH2:18][C:17]1[CH:21]=[CH:22][C:14]([Cl:13])=[CH:15][CH:16]=1)#[N:2]
Reactant: NCCc1ccc(Cl)cc1
Reactant: COC(=NC#N)c1ccccn1
Solvent: CO
Product: N#CNC(=NCCc1ccc(Cl)cc1)c1ccccn1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 48.4 %

Procedure:
Methyl N-cyano-2-pyridinecarboximidate (0.50 g, 3.1 mmol) was dissolved in methanol (10 ml), 4-chlorophenethylamine (0.53 g, 3.4 mmol) was added, and the resulting mixture was stirred at room temperature for 30 minutes. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue thus obtained was crystallized from dichloromethane-diethyl ether to give the title compound (0.43 g, 1.5 mmol, yield: 49%) as colorless needles.
Reaction SMILES: C([N:4]1[CH2:8][C@H:7]([O:9][CH2:10][CH3:11])[C@H:6]([NH:12][C:13]2[C:18]([CH2:19][CH3:20])=[N:17][C:16]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[Cl:28])=[C:15]([CH2:29][CH3:30])[N:14]=2)[CH2:5]1)(=O)C.Cl[C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33]>>[Cl:28][C:22]1[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:21]=1[C:16]1[N:17]=[C:18]([CH2:19][CH3:20])[C:13]([NH:12][C@H:6]2[C@@H:7]([O:9][CH2:10][CH3:11])[CH2:8][N:4]([C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33])[CH2:5]2)=[N:14][C:15]=1[CH2:29][CH3:30]
Reactant: CC(C)OC(=O)Cl
Reactant: CCO[C@H]1CN(C(C)=O)C[C@H]1Nc1nc(CC)c(-c2ccc(Cl)cc2Cl)nc1CC
Product: CCO[C@H]1CN(C(=O)OC(C)C)C[C@H]1Nc1nc(CC)c(-c2ccc(Cl)cc2Cl)nc1CC

Procedure:
Following the procedure for the preparation of N-[(cis)-1-acetyl-4-ethoxypyrrolidin-3-yl]-5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-amine but substituting isopropyl chloroformate and making non-critical variations provided the title compound as an oil: 1H NMR (400 MHz, CDCl3) δ) 7.49, 7.34-7.26, 5.22, 4.95, 4.75, 4.08, 3.96, 3.73, 3.60, 3.50, 3.38, 3.25, 2.71, 2.47, 1.32-1.25, 1.16; HRMS (FAB) calcd for C24H32Cl2N4O3+H 495.1929, found 495.1909. Anal. Calcd for C24H32Cl2N4O3: C, 58.18; H, 6.51; N, 11.31. Found: C, 58.43; H, 6.64; N, 11.25.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[CH2:11][OH:12])=[CH:5][C:4]=1[O:13][CH2:14][C:15]1[N:16]=[C:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:18][C:19]=1[CH3:20]>[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][CH:11]=[O:12])=[CH:5][C:4]=1[O:13][CH2:14][C:15]1[N:16]=[C:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:18][C:19]=1[CH3:20]
Reactant: COc1ccc(/C=C/CO)cc1OCc1nc(-c2ccccc2)oc1C
Agent: [Mn+4]
Agent: [O-2]
Product: COc1ccc(C=CC=O)cc1OCc1nc(-c2ccccc2)oc1C

Procedure:
In substantially the same manner as in Reference Example 35, (E)-3-[4-methoxy-3-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]-2-propen-1-ol was subjected to oxidation with activated manganese dioxide to yield 4-methoxy-3-(5-methyl-2-phenyl-4-oxazolylmethoxy)cinnam aldehyde, which was recrystallized from ethyl acetate-ether to give pale yellow needles, m.p.136-137° C.
Reaction SMILES: [OH:1]O.[CH2:3]([S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([NH2:20])(=[O:19])=[O:18])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C(O)(=O)C>[CH2:3]([S:10]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17]([NH2:20])(=[O:19])=[O:18])=[O:1])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: OO
Reactant: NS(=O)(=O)c1ccccc1SCc1ccccc1
Solvent: CC(=O)O
Product: NS(=O)(=O)c1ccccc1S(=O)Cc1ccccc1
Reaction time: 5 h
Yield: 94.6 %

Procedure:
102 ml of 30% hydrogen peroxide solution are added dropwise at a temperature of +10° C. to a solution of 219 g of 2-benzylthiophenylsulfonamide obtained in accordance with Example P1 in 500 ml of concentrated acetic acid. The reaction mixture is then stirred for 5 hours at a temperature of +25° C., the product slowly crystallising out. After separating off the crystals, washing with water and drying, 219 g (94.6%) of 2-benzylsulfinylphenylsulfonamide are obtained in the form of colour less crystals having a melting point of from +206° to ÷209° C.
Reaction SMILES: [N:1]1([CH2:6][C:7]23[CH2:16][CH:11]4[CH2:12][CH:13]([CH2:15][C:9]([O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][OH:26])([CH2:10]4)[CH2:8]2)[CH2:14]3)[CH:5]=[CH:4][CH:3]=[N:2]1.[Li][CH2:28]CCC.IC>O1CCCC1>[CH3:28][C:5]1[N:1]([CH2:6][C:7]23[CH2:14][CH:13]4[CH2:12][CH:11]([CH2:10][C:9]([O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][OH:26])([CH2:15]4)[CH2:8]2)[CH2:16]3)[N:2]=[CH:3][CH:4]=1
Reactant: OCCOCCOCCOC12CC3CC(CC(Cn4cccn4)(C3)C1)C2
Reactant: [Li]CCCC
Solvent: C1CCOC1
Solvent: CI
Product: Cc1ccnn1CC12CC3CC(C1)CC(OCCOCCOCCO)(C3)C2
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a cold (−78° C.) solution of EXAMPLE 83A (1.0 g) in tetrahydrofuran (10 mL) was added n-BuLi (5 mL, 2.5 M in hexane). The reaction mixture was stirred for 90 minutes, and iodomethane (1 mL) was added. The reaction mixture was stirred at −78° C. for 90 minutes and quenched by the addition of 1 drop of trifluoroacetic acid. The reaction mixture was warmed to room temperature and concentrated to dryness. The residue was used in the subsequent step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]3[CH:10]=[C:11]([CH2:14][C:15]([OH:17])=[O:16])[CH:12]=[CH:13][C:7]=3[C:6]=2[CH:18]=1.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:26][N:27]([CH2:29][CH2:30]Cl)[CH3:28]>CN(C)C=O>[ClH:1].[CH3:26][N:27]([CH3:28])[CH2:29][CH2:30][O:16][C:15](=[O:17])[CH2:14][C:11]1[CH:12]=[CH:13][C:7]2[C:6]3[CH:18]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[S:9][C:8]=2[CH:10]=1
Reactant: CN(C)CCCl
Reactant: O=C(O)Cc1ccc2c(c1)sc1ccc(Cl)cc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CN(C)CCOC(=O)Cc1ccc2c(c1)sc1ccc(Cl)cc12

Procedure:
A mixture of 2.76 g. of 8-chlorodibenzothiophene-3-acetic acid, 3.04 g. of potassium carbonate, 1.73 g. of dimethylaminoethyl chloride hydrochloride, and 250 ml. of dimethylformamide was stirred and heated at 120° for 4 hours. The solvent was removed in vacuo on the steam bath, and 75 ml. of water added to the residue. The oil was extracted with ethyl acetate and the crude product precipitated as the hydrochloride by the addition of hydrogen chloride. On crystallization from acetone, 1.5 g. of 8-chlorodibenzothiophene-3-acetic acid 2-dimethylaminoethyl ester hydrochloride, m.p. 179°-181°, was obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][S:8][CH2:9][CH2:10][NH:11]C(=O)OC(C)(C)C.Cl>C(O)C.C1(C)C=CC=CC=1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][S:8][CH2:9][CH2:10][NH2:11]
Reactant: CC(C)(C)OC(=O)NCCSSc1ccccn1
Agent: Cl
Solvent: CCO
Solvent: Cc1ccccc1
Product: NCCSSc1ccccn1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 19.6 %

Procedure:
tert-Butyl 2-(pyridin-2-yldisulfanyl)ethylcarbamate (1.06 g, 3.70 mmol) in 16 ml of EtAc was added 4.0 ml of HCl (conc.) at RT. The mixture was stirred at RT for 0.5 h, diluted with ethanol/toluene (6 ml, 1:1), evaporated and co-evaporated with ethanol/toluene (3×10 ml), crystallized with ethanol/EtAc/Hexane, filtered, and dried over a vaccum to afford 135 mg (88%) of the title compound. 1H NMR (CD3OD) 7.58 (m, 1H), 7.47 (m, 1H), 7.06 (m, 1H), 6.83 (m, 1H), 3.34 (m, 2H), 3.02 (m, 2H); 13C NMR 158.69, 149.07, 137.81, 122.48, 120.98, 39.52, 36.94; MS m/z+ 187.10 (M+H).
Reaction SMILES: C(O)(=O)C.[Si:5]([O:12][CH2:13][CH:14]=O)([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:30]([O:37][C:38]1[CH:62]=[CH:61][C:60]([CH:63]2[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]2)=[CH:59][C:39]=1[C:40]([NH:42][C:43]1[CH:52]=[C:51]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH:50]=[CH:49][C:44]=1[C:45]([O:47][CH3:48])=[O:46])=[O:41])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1>[CH2:30]([O:37][C:38]1[CH:62]=[CH:61][C:60]([CH:63]2[CH2:64][CH2:65][N:66]([CH2:14][CH2:13][O:12][Si:5]([C:8]([CH3:9])([CH3:10])[CH3:11])([CH3:6])[CH3:7])[CH2:67][CH2:68]2)=[CH:59][C:39]=1[C:40]([NH:42][C:43]1[CH:52]=[C:51]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH:50]=[CH:49][C:44]=1[C:45]([O:47][CH3:48])=[O:46])=[O:41])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: CC(C)(C)[Si](C)(C)OCC=O
Reactant: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCNCC2)ccc1OCc1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 13 h

Procedure:
Acetic acid (0.023 mL), 2-(tert-butyldimethylsilyloxy)acetaldehyde (0.046 mL), and sodium triacetoxyborohydride (0.11 g) were sequentially added to a tetrahydrofuran (1.0 mL) solution of methyl 2-(2-(benzyloxy)-5-(piperidin-4-yl)benzamido)-4-phenylbenzoate (0.11 g), followed by stirring at room temperature for 13 hours. The solvent was evaporated under reduced pressure, and ethyl acetate was added to the residue. After removal of the insoluble substance by filtration, a saturated aqueous solution of sodium bicarbonate was added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-92% chloroform/methanol] to obtain 0.13 g of methyl 2-(2-(benzyloxy)-5-(1-(2-(tert-butyldimethylsilyloxy)ethyl)piperidin-4-yl)benzamido)-4-phenylbenzoate as a white solid.
Reaction SMILES: [CH:1]1[C:6]2[C:7]3[C:16]([CH2:17][CH2:18][C:5]=2[CH:4]=[C:3]([CH:19]=[O:20])[CH:2]=1)=[CH:15][C:14]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=1[CH:8]=3.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1(C)C=CC=CC=1>[CH:1]1[C:6]2=[C:7]3[C:16](=[CH:17][CH:18]=[C:5]2[CH:4]=[C:3]([CH:19]=[O:20])[CH:2]=1)[CH:15]=[C:14]1[C:9]([CH:10]=[CH:11][CH:12]=[CH:13]1)=[CH:8]3
Reactant: O=Cc1ccc2c(c1)CCc1cc3c(cc1-2)CCCC3
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: Cc1ccccc1
Product: O=Cc1ccc2c(ccc3cc4ccccc4cc32)c1
Yield: 28.9 %

Procedure:
To a RB flask equipped with magnetic stirring bar, reflux condenser and N2 inlet line with bubbler added 5,6,8,9,10,11-hexahydrobenz[a]anthracene-3-carbaldehyde (7A, 10.41 g, 39.7 mmol), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (Aldrich, 27.02 g, 0.119 mol) and dry PhCH3 (500 mL). The mixture was refluxed for 2 h until no more starting material remained by TLC, cooled and filtered to give a deep red solution. The solution was applied to a 40×10 cm column of SiO2 and eluted with additional PhCH3 as the solvent. The appropriate fractions were combined and the solvent removed to give 6.01 g of crude material. This was crystallized twice from PhCH3 /hexane (1:4) and dried to give 2.94 g (28.9% yield) of benz[a]anthracene-3-carbaldehyde, mp 144°-145°, (C, H).
Reaction SMILES: [Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].[CH3:12][NH:13][O:14][CH3:15].CCN(CC)CC.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(Cl)Cl>[Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([N:13]([O:14][CH3:15])[CH3:12])=[O:5]
Reactant: Cc1cccc(C(=O)O)c1Cl
Reactant: CNOC
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CON(C)C(=O)c1cccc(C)c1Cl
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.7 %

Procedure:
To a cooled mixture of 2-chloro-3-methyl-benzoic acid (1 g, 5.88 mmol), N,O-dimethylhydroxylamine (860 mg, 8.82 mmol) and Et3N (3.27 mL, 23.52 mmol) in CH2Cl2 (10 mL) was added 1-propane phosphonic acid cyclic anhydride (4.49 mL, 7.05 mmol; 50 wt % solution in EtOAc) dropwise and stirred at room temperature for 3 h. The reaction mixture was filtered, washed with CH2Cl2 (2×10 mL), evaporated to dryness and subjected to column chromatography (SiO2, 40% EtOAc-hexanes) to obtain 2-chloro-N-methoxy-3,N-dimethyl-benzamide (1.19 g) in 95% yield. ESMS m/z (relative intensity): 214 (M+H)+ (100).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]([O:11][CH3:12])=[O:10])[CH:5]=[C:4]([O:13][S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[N:3]=1.ClC1C=CC=C(C(OO)=[O:32])C=1>C(Cl)Cl.CO>[NH2:1][C:2]1[N+:7]([O-:32])=[C:6]([NH:8][C:9]([O:11][CH3:12])=[O:10])[CH:5]=[C:4]([O:13][S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[N:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COC(=O)Nc1cc(OS(=O)(=O)c2ccc(C)cc2)nc(N)n1
Solvent: ClCCl
Solvent: CO
Product: COC(=O)Nc1cc(OS(=O)(=O)c2ccc(C)cc2)nc(N)[n+]1[O-]

Procedure:
350 g of methyl 2-amino-6-[(p-tolylsulfonyl)oxy]-4-pyrimidinecarbamate are suspended in 6.3 l of methylene chloride and 1 l of methanol. At room temperature there are added thereto 370 g of m-chloroperbenzoic acid and the mixture is stirred for a further 16 hours. The yellowish solution is subsequently extracted with 3 l of 2N soda solution. The aqueous phase is extracted with 1 l of methylene chloride. The combined organic phases are washed with 2 l of water and evaporated in vacuo. The crystalline residue is suspended in 1.5 l of ether while stirring. The pale yellowish crystals are filtered off under suction and washed with 0.5 l of ether. After drying at 40° in vacuo, there is obtained methyl 2-amino-6-[(p-tolylsulfonyl)oxy]-4-pyrimidinecarbamate-3-oxide.
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][N:12]([CH:14]3[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)[CH:13]=2)[O:3]1.[ClH:28].CC(=O)OCC>CC(=O)OCC>[ClH:28].[CH3:1][C:2]1([CH3:27])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:10]=[N:11][N:12]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH:13]=2)[O:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(n2cc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Agent: Cl
Solvent: CCOC(C)=O
Product: CC1(C)OB(c2cnn(C3CCNCC3)c2)OC1(C)C

Procedure:
A solution of tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (8.2 g, 21.73 mmol) and 30 mL of HCl-EA (5.0 N) in 15 mL of EA was stirred at room temperature for 2 hours. The volatiles were removed in vacuo to give 7.3 g of title compound.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[CH:11](O)([CH3:13])[CH3:12]>>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH:11]([CH3:13])[CH3:12])=[O:7])=[CH:4][CH:3]=1
Reactant: CC(C)O
Reactant: O=C(O)c1ccc(Br)cc1
Product: CC(C)OC(=O)c1ccc(Br)cc1
Yield: 97 %

Procedure:
Using General Esterification Procedure A; 4-bromobenzoic acid (1.50 g, 7.46 mmols) was combined with isopropyl alcohol to give 1.76 g (97%) of the title compound as a colorless oil.
Reaction SMILES: [C:1]([C:5]1[CH:38]=[CH:37][C:8]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]3[N:19]=[C:20]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][CH:29]=4)[C:21]4[N:22]([CH:24]=[CH:25][N:26]=4)[CH:23]=3)[C:13]=2[CH3:36])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[ClH:39].[CH2:40]([OH:42])[CH3:41]>>[ClH:39].[CH2:40]([O:42][C:34](=[NH:35])[C:31]1[CH:30]=[CH:29][C:28]([NH:27][C:20]2[C:21]3[N:22]([CH:24]=[CH:25][N:26]=3)[CH:23]=[C:18]([C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([NH:11][C:9](=[O:10])[C:8]4[CH:37]=[CH:38][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6][CH:7]=4)[C:13]=3[CH3:36])[N:19]=2)=[CH:33][CH:32]=1)[CH3:41]
Reactant: CCO
Reactant: Cc1c(NC(=O)c2ccc(C(C)(C)C)cc2)cccc1-c1cn2ccnc2c(Nc2ccc(C#N)cc2)n1
Agent: Cl
Product: CCOC(=N)c1ccc(Nc2nc(-c3cccc(NC(=O)c4ccc(C(C)(C)C)cc4)c3C)cn3ccnc23)cc1
Temperature: 0 °C

Procedure:
4-tert-Butyl-N-{3-[8-(4-cyano-phenylamino)-imidazo[1,2-a]pyrazin-6-yl]-2-methyl-phenyl}-benzamide is slurried in 200 mL ethanol (200 proof) and the reaction cooled to 0° C. in an ice bath. The reaction is then saturated with hydrogen chloride gas and allowed to gradually warm to rt over 16 hrs with stirring. The solvent is removed in vacuo and the resulting tan solid 4-{6-[3-(4-tert-butyl-benzoylamino)-2-methyl-phenyl]-imidazo[1,2-a]pyrazin-8-ylamino}-benzimidic acid ethyl ester hydrochloride (500 mg) is used without further purification.