Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[NH:21][S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:24])=[O:23].[C:31]1([CH3:41])[C:32]([S:37](Cl)(=[O:39])=[O:38])=[CH:33][CH:34]=[CH:35][CH:36]=1>>[CH3:41][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[S:37]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[CH:4][C:3]=1[NH:21][S:22]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)(=[O:23])=[O:24])(=[O:39])=[O:38]
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(N)c(NS(=O)(=O)c3ccccc3)c2)CC1
Product: Cc1ccccc1S(=O)(=O)Nc1ccc(N2CCNCC2)cc1NS(=O)(=O)c1ccccc1

Procedure:
2-Methyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide was synthesized from N-{2-amino-5-(4-t-butyloxycarbonyl-piperazinyl)-phenyl}benzenesulfonamide and o-toluenesulfonylchloride is (46 mg, 0.239 mmol) according to general method 3 to give before Boc-deprotection 160 mg of a purple solid. MS (posES-FIA) m/z=Found 487.1; Calcd 487.14; 1H-NMR δ 7.74-7.16 (m, 8H), 6.78-6.52 (m, 4H), 3.27-3.16 (m, 8H), 2.58 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH:17]=[CH:16][S:15][C:10]=2[NH:11][C:12](=[O:14])[N:13]=1.[H-].[Na+].[CH3:20]I.O>CN(C)C=O>[CH3:20][O:14][C:12]1[N:13]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[C:9]2[CH:17]=[CH:16][S:15][C:10]=2[N:11]=1
Reactant: CI
Reactant: O=c1nc(-c2ccccc2F)c2ccsc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1nc(-c2ccccc2F)c2ccsc2n1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
To a solution of 9.49 g of 4-(o-fluorophenyl)-1,2-dihydrothieno[2,3-d]pyrimidin-2-one in 200 ml of dimethylformamide is added 1.76 g of 63% sodium hydride. The mixture is stirred at 60°C for 1 hour. The mixture is cooled to room temperature and 10.93 g of methyl iodide in 33 ml of dimethylformamide is added dropwise thereto. The mixture is stirred for 2 hours at room temperature. The reaction mixture is poured into water and extracted with chloroform. The chloroform extracts are washed with water, dried over sodium sulfate, and the solvent is removed under reduced pressure. The residue is chromatographed on silica gel, using chloroform as an eluent. From the first fraction, 2-methoxy-4-(o-fluorophenyl)-thieno[2,3-d]pyrimidine is obtained as crystals having a melting point of 175° - 176.5°C (after recrystallization from ethanol). From the second fraction, 1-methyl-4-(o-fluorophenyl)-1,2-dihydrothieno[2,3-d]pyrimidin-2-one is obtained as crystals having a melting point of 222° - 223°C (after recrystallization from ethanol). From the third fraction, 3-methyl-4-(o-fluorophenyl)-3H-thieno[2,3-d]pyrimidin-2-one is obtained as crystals having a melting point of 191° - 192.5°C (after recrystallization from ethanol).
Reaction SMILES: C1(C(=NC([CH2:21][CH2:22][C:23]2[CH:24]=[C:25]3[C:48](=[CH:49][CH:50]=2)[C:29]2=[N:30][O:31][C:32]([C:33]4[C:37]([C:38]([F:41])([F:40])[F:39])=[C:36]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[O:35][N:34]=4)=[C:28]2[CH2:27][CH2:26]3)C(OCC)=O)C2C=CC=CC=2)C=CC=CC=1.[C:51]([O:55][C:56]([NH:58][CH:59]([C:65]([O:67][CH2:68][CH3:69])=[O:66])[C:60]([O:62][CH2:63][CH3:64])=[O:61])=[O:57])([CH3:54])([CH3:53])[CH3:52]>>[C:51]([O:55][C:56]([NH:58][C:59]([CH2:21][CH2:22][C:23]1[CH:24]=[C:25]2[C:48](=[CH:49][CH:50]=1)[C:29]1=[N:30][O:31][C:32]([C:33]3[C:37]([C:38]([F:40])([F:41])[F:39])=[C:36]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[O:35][N:34]=3)=[C:28]1[CH2:27][CH2:26]2)([C:60]([O:62][CH2:63][CH3:64])=[O:61])[C:65]([O:67][CH2:68][CH3:69])=[O:66])=[O:57])([CH3:54])([CH3:52])[CH3:53]
Reactant: CCOC(=O)C(CCc1ccc2c(c1)CCc1c-2noc1-c1noc(-c2ccccc2)c1C(F)(F)F)N=C(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)C(NC(=O)OC(C)(C)C)C(=O)OCC
Product: CCOC(=O)C(CCc1ccc2c(c1)CCc1c-2noc1-c1noc(-c2ccccc2)c1C(F)(F)F)(NC(=O)OC(C)(C)C)C(=O)OCC
Temperature: 70 °C

Procedure:
The titled compound was prepared using the experimental protocol described for Preparation 91A employing diethyl 2-(tert-butoxycarbonylamino)malonate as a starting material. The reaction was heated at 70° C. for 7 hr. The compound had an LC/MS [M-Boc]+1=584.5.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[OH:32][C:33]1[CH:37]=[C:36]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[O:35][N:34]=1.[C:44]([O:48][C:49]([NH:51][CH2:52][CH2:53]O)=[O:50])([CH3:47])([CH3:46])[CH3:45]>O1CCCC1>[C:44]([O:48][C:49]([NH:51][CH2:52][CH2:53][O:32][C:33]1[CH:37]=[C:36]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[O:35][N:34]=1)=[O:50])([CH3:47])([CH3:46])[CH3:45]
Reactant: Oc1cc(-c2ccccc2)on1
Reactant: CC(C)(C)OC(=O)NCCO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCOc1cc(-c2ccccc2)on1
Temperature: 25 °C
Yield: 69.5 %

Procedure:
Triphenylphosphine (0.87 g) was dissolved in tetrahydrofuran (10 ml), and diethyl azodicarboxylate (0.57 g) was added dropwise to the solution under ice-cooling with stirring, and the mixture was stirred at the same temperature for 10 minutes. 3-Hydroxy-5-phenylisoxazole (0.48 g) and 2-(N-tert-butoxycarbonylamino)ethanol (0.48 g) were added to the reaction mixture, and the resulting mixture was stirred under ice-cooling for 10 minutes and at room temperature for 24 hours. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: cyclohexane/ethyl acetate=4/1) and was crystallized from isopropyl ether to obtain the title compound (0.63 g, 69%) as colorless crystals.
Reaction SMILES: [NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[C:17]([F:18])=[C:16]3[C:12]([CH:13]=[CH:14][NH:15]3)=[CH:11][CH:10]=2)[N:5]=[C:4]([C:19]([O:21]C)=[O:20])[C:3]=1[Cl:23].[OH-].[Na+].Cl>CO>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[C:17]([F:18])=[C:16]3[C:12]([CH:13]=[CH:14][NH:15]3)=[CH:11][CH:10]=2)[N:5]=[C:4]([C:19]([OH:21])=[O:20])[C:3]=1[Cl:23]
Reactant: COC(=O)c1nc(-c2ccc3cc[nH]c3c2F)c(F)c(N)c1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Nc1c(F)c(-c2ccc3cc[nH]c3c2F)nc(C(=O)O)c1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.3 %

Procedure:
To a reaction vessel containing methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinate (0.500 g, 1.481 mmol) was added methanol (14.81 ml) and sodium hydroxide (2.96 ml, 5.92 mmol). The reaction mixture was stirred overnight at rt then acidfied by adding a slight excess of 2N HCl. The mixture was concentrated and the precipitate that formed was washed with water and dried under vacuum to provide 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinic acid (0.400 g, 1.174 mmol, 79% yield) as an off-white solid:
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([CH:16]=[O:17])=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[P:19]([O-:24])([O:22][CH3:23])[O:20][CH3:21]>C1COCC1.CCOC(C)=O>[CH2:1]([O:8][C:9](=[O:18])[C:10]1[CH:11]=[CH:12][C:13]([CH:16]([P:19]([O:22][CH3:23])([O:20][CH3:21])=[O:24])[OH:17])=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COP([O-])OC
Reactant: O=Cc1ccc(C(=O)OCc2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COP(=O)(OC)C(O)c1ccc(C(=O)OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
A solution of 4-formyl-benzoic acid benzyl ester (0.50 g, 2.08 mmol) in THF (2.0 mL) was cooled to 0° C., then dimethyl phosphite (0.25 g, 2.29 mmol) and N,N,N′M′-tetramethyl-guanidine (0.02 g, 0.21 mmol) was added dropwise. The reaction mixture was warmed to ambient temperature. After stirring for 45 mins the reaction mixture was diluted with EtOAc and washed with 1N aqueous HCl (2×), brine, then dried (MgSO4) and concentrated in vacuo to give the title compound: MS: cal'd 351 (MH+), exp 351 (MH+)
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([NH:6][CH3:7])=[C:4]([N+:10]([O-:12])=[O:11])[C:3]=1F.[C:14]1([OH:20])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([NH:6][CH3:7])=[C:4]([N+:10]([O-:12])=[O:11])[C:3]=1[O:20][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CNc1ccc(Br)c(F)c1[N+](=O)[O-]
Reactant: Oc1ccccc1
Product: CNc1ccc(Br)c(Oc2ccccc2)c1[N+](=O)[O-]

Procedure:
This compound was synthesized according to the procedure of Example 1, Step 1, using 4-bromo-3-fluoro-N-methyl-2-nitroaniline and phenol as the starting materials. LCMS calculated for C13H12BrN2O3 (M+H)+: m/z=323.0, 325.0. found: 322.9, 325.0.
Reaction SMILES: C(=O)(O)[O-].[Na+].Cl.[NH2:7][CH2:8][CH2:9][SH:10].[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@@H:19]1[C:23](F)=[O:24])=[O:17])([CH3:14])([CH3:13])[CH3:12]>O.C(Cl)Cl>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@@H:19]1[C:23](=[O:24])[NH:7][CH2:8][CH2:9][SH:10])=[O:17])([CH3:14])([CH3:13])[CH3:12]
Reactant: NCCS
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1C(=O)F
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC[C@@H]1C(=O)NCCS
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
To a 50 mL round-bottom flask charged with a solution of sodium bicarbonate (134.3 mg, 1.6 mmol) in 7.8 mL water was added 2-aminoethanethiol hydrochloride (97.5 mg, 0.86 mmol). To this stirring solution was added dropwise over 60 seconds a solution of 25d (170.3 mg, 0.78 mmol) in 7.8 mL CH2Cl2. The reaction was vigorously stirred for 25 minutes at room temperature, then extracted twice with fresh CH2Cl2. The combined CH2Cl2 extracts were washed once with 5% aqueous HCl, once with 10% aqueous sodium bicarbonate, then once with water. The organic fraction was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford 205.8 mg (96% from 24d) of clean 26d as a colorless oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[CH2:7]OC1C=CC(Cl)=CC=1Br)([CH3:4])([CH3:3])[CH3:2].[Br:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([I:26])[CH:20]=1>>[Br:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:17])=[C:21]([I:26])[CH:20]=1
Reactant: CC(C)(C)OC(=O)COc1ccc(Cl)cc1Br
Reactant: Oc1ccc(Br)cc1I
Product: CC(C)(C)OC(=O)COc1ccc(Br)cc1I

Procedure:
Following the general method as outlined in Intermediate 1, starting from 4-bromo-2-iodophenol (Intermediate 189), the title compound was obtained as a brown oil after purification by flash column chromatography (silica), eluting with 2% methanol in chloroform.
Reaction SMILES: C[Si](C)(C)Cl.Br[CH2:7][C:8]([O:10][CH3:11])=[O:9].[C:12]1([CH2:18][CH2:19][C:20](=[O:24])[CH2:21][CH2:22][CH3:23])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)C1C=CC=CC=1.CC(=O)CCC.C1(C=CC(=O)CCC)C=CC=CC=1.Cl>C(OC(C)C)(=O)C.[Zn]>[OH:24][C:20]([CH2:19][CH2:18][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)([CH2:21][CH2:22][CH3:23])[CH2:7][C:8]([O:10][CH3:11])=[O:9]
Reactant: CCCC(=O)CCc1ccccc1
Reactant: COC(=O)CBr
Agent: CCCC(=O)C=Cc1ccccc1
Agent: C[Si](C)(C)Cl
Agent: Cl
Solvent: CC(=O)OC(C)C
Solvent: CCCC(C)=O
Solvent: O=Cc1ccccc1
Product: CCCC(O)(CCc1ccccc1)CC(=O)OC
Temperature: 60 °C
Reaction time: 0.25 h

Procedure:
At room temperature, a three-neck flask equipped with a reflux condenser, internal thermometer, dropping funnel and stirrer under nitrogen protective gas was initially charged with 7.9 g of zinc powder (121 mmol) in 45 ml of isopropyl acetate. After 1.83 ml of trimethylchlorosilane (12.6 mmol) had been added, the mixture was heated to 60° C. for 15 min, then allowed to cool to 55° C. and 17.7 g of methyl bromoacetate (115 mmol) were added within 5 min, and the temperature of the mixture was maintained at 60° C. by external cooling. The mixture was then stirred at 50° C. for 15 min. After cooling to 40° C., 15.7 g of undiluted 1-phenylhexan-3-one (89 mmol, prepared by base-catalyzed aldol condensation of benzaldehyde and pentan-2-one and subsequent hydrogenation of the 1-phenylhex-1-en-3-one obtained) were added, and the temperature was maintained at 50° C. by external cooling. The mixture was then stirred at 60° C. for 45 min and, after cooling to 15° C., acidified with 20 ml of 20% hydrochloric acid to a pH of 1 and stirred for 30 min. Excess zinc was then filtered off and the organic phase was removed. The organic phase was then stirred with 30 ml of concentrated ammonia solution at 0° C. for 10 min. After the phase separation, drying was effected over sodium sulfate and the solvent was distilled off under reduced pressure. Methyl 3-hydroxy-3-(2-phenylethyl)hexanoate was obtained in a yield of 21.1 g (95% of theory) and a purity of >95% (HPLC).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:29]=[O:30]>O1CCCC1>[C:16]1([C@H:14]([N:10]2[CH2:11][CH2:12][O:13][C@@H:8]([C:5]3[CH:6]=[CH:7][C:2]([CH:29]=[O:30])=[CH:3][CH:4]=3)[CH2:9]2)[CH3:15])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: C[C@H](c1ccccc1)N1CCO[C@@H](c2ccc(Br)cc2)C1
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C[C@H](c1ccccc1)N1CCO[C@@H](c2ccc(C=O)cc2)C1
Temperature: -10 °C
Reaction time: 0.33 h
Yield: 101.9 %

Procedure:
To a solution of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (intermediate 7, 63.3 g, 183 mmol) in tetrahydrofuran (450 ml) was added n-butyllithium (1.57 M in hexane solution, 175 ml, 275 mmol) at −78° C. and the mixture was stirred for 20 minutes. N,N-dimethylformamide (28.3 ml 365 mmol) was added and the mixture was stirred for 2 hours at −78° C. and then allowed to be warmed to −10° C. The reaction was quenched with aqueous ammonium chloride, and the resulting solution was partitioned between water and ethyl acetate. The organic layer was washed with water and brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure to afford crude 4-((2S)-4-((1R)-1-phenylethyl) morpholin-2-yl)benzaldehyde (intermediate 8, 55.1 g). This compound was used without further purification.
Reaction SMILES: [CH3:1][C:2]1([CH3:29])[CH2:7][CH:6]([O:8][C:9](=[O:26])[CH:10]([CH2:24][CH3:25])[C:11]([O:13][CH:14]2[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]2)=[O:12])[CH2:5][C:4]([CH3:28])([CH3:27])[NH:3]1.[H-].[Na+].[CH3:32][C:33]1[C:40]([OH:41])=[C:39]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:38]=[C:37]([CH3:46])[C:34]=1[CH2:35]Cl>CN(C)C=O>[CH3:21][C:18]1([CH3:20])[CH2:19][CH:14]([O:13][C:11](=[O:12])[C:10]([CH2:24][CH3:25])([CH2:35][C:34]2[C:37]([CH3:46])=[CH:38][C:39]([C:42]([CH3:45])([CH3:44])[CH3:43])=[C:40]([OH:41])[C:33]=2[CH3:32])[C:9]([O:8][CH:6]2[CH2:7][C:2]([CH3:1])([CH3:29])[NH:3][C:4]([CH3:28])([CH3:27])[CH2:5]2)=[O:26])[CH2:15][C:16]([CH3:23])([CH3:22])[NH:17]1
Reactant: CCC(C(=O)OC1CC(C)(C)NC(C)(C)C1)C(=O)OC1CC(C)(C)NC(C)(C)C1
Reactant: Cc1cc(C(C)(C)C)c(O)c(C)c1CCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCC(Cc1c(C)cc(C(C)(C)C)c(O)c1C)(C(=O)OC1CC(C)(C)NC(C)(C)C1)C(=O)OC1CC(C)(C)NC(C)(C)C1
Temperature: 0 °C
Reaction time: 20 h

Procedure:
To 24.6 g (0.06 mole) of ethylmalonic acid-bis(2,2,6,6-tetramethyl-4-piperidinyl)ester in 80 ml of dimethylformamide there are added 2.5 g of NaH dispersion (55-60%) followed by 13.6 g (0.06 mole) of 2,6-di-methyl-4-tert. butyl-3-hydroxybenzyl chloride in 40 ml of DMF. The reaction mixture is stirred for 20 hours at 90°-100° C. and is then poured into ice-water; the aqueous solution is extracted with ether, the ethereal solution is dried over Na2SO4, and after removal of the solvent in vacuo there is obtained ethyl-(2,6-dimethyl-4-tert.butyl-3-hydroxybenzyl)malonic acid-bis (2,2,6,6-tetramethyl-4-piperidinyl)ester in the form of an oily yellowish residue (No. 43).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.C(=O)(O)[O-].[Na+].[CH3:15][CH:16]1[CH2:20][CH2:19][CH2:18][NH:17]1>CO>[Cl:9][C:4]1[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([N:17]2[CH2:18][CH2:19][CH2:20][CH:16]2[CH3:15])[N:3]=1
Reactant: Clc1cc(Cl)nc(Cl)n1
Reactant: CC1CCCN1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: CC1CCCN1c1nc(Cl)cc(Cl)n1
Temperature: 0 °C
Reaction time: 16 h

Procedure:
Dissolve 2,4,6-trichloropyrimidine (23.5 g, 0.13 mol) in anhydrous MeOH (220 mL), and add solid sodium bicarbonate (28.3 g, 0.33 mol). Cool to 0° C. and add 2-methylpyrrolidine (12 g, 0.14 mol) dropwise. Let stir at room temperature for 16 h. Filter off the excess sodium bicarbonate, and evaporate under reduced pressure. Purify by SiO2 liquid chromatography, using 50:1 hexanes:EtOAc, increasing to 30:1 hexanes:EtOAc, to provide the title compound as a white solid.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][OH:7].[C:8]1(=O)[O:13][C:11](=[O:12])[CH:10]2[CH2:14][CH2:15][CH2:16][CH2:17][CH:9]12>C(O)C>[OH:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][N:1]1[C:11](=[O:12])[CH:10]2[CH2:14][CH2:15][CH2:16][CH2:17][CH:9]2[C:8]1=[O:13]
Reactant: O=C1OC(=O)C2CCCCC12
Reactant: NCCOCCO
Solvent: CCO
Product: O=C1C2CCCCC2C(=O)N1CCOCCO
Yield: 95.6 %

Procedure:
A 500-ml, two necked flask was equipped with a magnetic stirring bar, heating mantle and condenser. The flask was charged with 51 g of 2-(aminoethoxy)ethanol (0.49 mol.) and 250 ml of ethanol. Next, 75 g of hexahydrophthalic anhydride (0.49 mol.) was slowly added to the flask. After the addition was complete the reaction was refluxed for 12 hours. The IR spectrum indicated the reaction was complete. The ethanol was removed with a rotoevaporator to yield 113 g (96%) of N-(2-hydroxyethoxyethyl)hexahydrophthalimide.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:14][O:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[CH:21][CH:22]=[C:23]2[CH2:26][CH2:27][NH:28][C:29](=[O:32])[CH2:30]Br)=[CH:18][CH:17]=1>CC(C)=O>[CH3:14][O:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[CH:21][CH:22]=[C:23]2[CH2:26][CH2:27][NH:28][C:29](=[O:32])[CH2:30][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:18][CH:17]=1
Reactant: C1COCCN1
Reactant: COc1ccc2cccc(CCNC(=O)CBr)c2c1
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: COc1ccc2cccc(CCNC(=O)CN3CCOCC3)c2c1

Procedure:
0.01 mol of morpholine is dissolved under magnetic agitation in 50 ml of acetone, and 0.012 mol of triethylamine and 0.01 mol of N-[2-(7-methoxynaphth-1-yl) ethyl]-2-bromoacetamide are added. The mixture is refluxed for 1 hour under magnetic agitation. The precipitate formed is spun down and the filtrate is evaporated. The residue is taken up in alkaline water, and the precipitate - is spun down, washed, dried and recrystallized in a toluene/cyclohexane mixture.
Reaction SMILES: [NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([CH:17]=[CH2:18])[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1>[Pd].C(O)C>[NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([CH2:17][CH3:18])[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1
Reactant: C=Cc1ccc2ccc3nc(N)[nH]c(=O)c3c2c1
Agent: [Pd]
Solvent: CCO
Product: CCc1ccc2ccc3nc(N)[nH]c(=O)c3c2c1
Yield: 65.2 %

Procedure:
A solution of 3-amino-9-vinylbenzo[f]quinazolin-1(2H)-one (0.060 g, 0.25 mmol) and 10% palladium on carbon (0.10 g) (Aldrich) in ethanol (200 ml) was shaken under hydrogen (40 psi) for 1 hour and then filtered through celite and concentrated in vacuo. The residue was suspended in ethanol, filtered, and dried at 85° C. under reduced pressure to give 3-amino-9-ethylbenzo[f]-quinazolin-1(2H)-one (0.039 g) as a white solid. 1H NMR (DMSO-d6, 200 MHz) δ: 1.26 (t, J=7 Hz, 3H, CH3), 2.76 (q, J=7 Hz, 2H, CH2), 6.49 (br s, 2H, NH2), 7.21 (d, J=9 Hz, 1H, Ar), 7.31(dd, J=8, 2 Hz, 1H, Ar), 7.77(d, J=8 Hz, Ar), 7.96 (d, J=g Hz, 1H, Ar), 9.47 (s, 1H, Ar), 11.08 (br s, 1H, NH). Mass spectrum (CI--CH4): 240 (M+1, 100%). Anal. Calculated for C14H13N3O0.1H2O: C, 69.75; H, 5.52; N, 17.43. Found: C, 69.79; H, 5.53; N, 17.37.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15](F)[C:14]=2[N+:20]([O-:22])=[O:21])[CH:3]=1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)[NH2:32])=[CH:27][CH:26]=1.C(N(C(C)C)C(C)C)C>CN1CCCC1=O>[CH3:40][O:39][C:36]1[CH:35]=[CH:34][C:33]([CH:31]([NH:32][C:15]2[C:14]([N+:20]([O-:22])=[O:21])=[C:13]([CH:18]=[CH:17][CH:16]=2)[O:12][C:4]2[CH:3]=[C:2]([F:1])[CH:11]=[CH:10][C:5]=2[C:6]([O:8][CH3:9])=[O:7])[C:28]2[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=2)=[CH:38][CH:37]=1
Reactant: COc1ccc(C(N)c2ccc(OC)cc2)cc1
Reactant: COC(=O)c1ccc(F)cc1Oc1cccc(F)c1[N+](=O)[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: COC(=O)c1ccc(F)cc1Oc1cccc(NC(c2ccc(OC)cc2)c2ccc(OC)cc2)c1[N+](=O)[O-]
Temperature: 100 °C

Procedure:
To a solution of EXAMPLE 403A (3.82 g) and bis(4-methoxyphenyl)methanamine (4.51 g) in N-methyl-2-pyrrolidinone (65 mL) was added N-ethyl-N-isopropylpropan-2-amine (4.30 mL) and the mixture was heated at 100° C. for 24 hours. The crude product, isolated by concentration, was purified on silica gel, and was eluted with a 10, 25, and 65% ethyl acetate in hexane step gradient to provide the title compound.
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[H-].[Na+].[CH3:13][N:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[CH2:24]Cl)[C:17]([CH3:26])=[CH:16][CH2:15]1>CN(C)C=O>[CH3:13][N:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[CH2:24][S:1][C:2]2[NH:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)[C:17]([CH3:26])=[CH:16][CH2:15]1
Reactant: Sc1nc2ccccc2[nH]1
Reactant: CC1=CCN(C)c2c(CCl)cccc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1=CCN(C)c2c(CSc3nc4ccccc4[nH]3)cccc21
Reaction time: 0.5 h
Yield: 32.3 %

Procedure:
2-Mercaptobenzimidazole (0.7 g) was dissolved in dimethyl formamide (30 ml). Sodium hydride (60% in oil, 0.19 g) was added thereto under ice-cooling and the mixture was stirred for 30 minutes. Sequentially, a solution of 1,4-dimethyl-8-chloromethyl-1,2-dihydroquinoline (0.8 g) in dimethyl formamide(5 ml) was added dropwise to the reaction mixture and the mixture was stirred for 1 hour under ice-cooling. After distilling off dimethyl formamide, the resulting residue was poured into an ice-cold water and the mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, then chloroform was distilled off. The resulting residue was purified by silica gel column chromatography [eluent : dichloromethane-methanol (200:1)] to give 1,4-dimethyl-8-(2-benzimidazolyl)thiomethyl-1,2-dihydroquinoline (0.4 g).
Reaction SMILES: C(C1C=CC(S([Cl:18])(=O)=O)=CC=1Cl)(=O)C1C=CC=CC=1.[Cl:20][C:21]1[CH:39]=[CH:38][C:24]([C:25]([C:27]2[CH:28]=[C:29]([S:34]([Cl:37])(=[O:36])=[O:35])[CH:30]=[CH:31][C:32]=2[Cl:33])=[O:26])=[CH:23][CH:22]=1.C(C1C=C(S(Cl)(=O)=O)C=CC=1Cl)(=O)C1C=CC=CC=1.ClC1C=CC(S(Cl)(=O)=O)=CC=1C(C1SC=CC=1)=O>>[Cl:18][C:23]1[CH:22]=[C:21]([Cl:20])[CH:39]=[CH:38][C:24]=1[C:25]([C:27]1[CH:28]=[C:29]([S:34]([Cl:37])(=[O:35])=[O:36])[CH:30]=[CH:31][C:32]=1[Cl:33])=[O:26]
Reactant: O=C(c1ccccc1)c1ccc(S(=O)(=O)Cl)cc1Cl
Reactant: O=C(c1ccc(Cl)cc1)c1cc(S(=O)(=O)Cl)ccc1Cl
Agent: O=C(c1ccccc1)c1cc(S(=O)(=O)Cl)ccc1Cl
Agent: O=C(c1cccs1)c1cc(S(=O)(=O)Cl)ccc1Cl
Product: O=C(c1ccc(Cl)cc1Cl)c1cc(S(=O)(=O)Cl)ccc1Cl

Procedure:
3-benzoyl-4-chlorobenzenesulphonyl chloride 3-(4-chlorobenzoyl)-4-chlorobenzenesulphonyl chloride 4-benzoyl-3-chlorobenzenesulphonyl chloride and 4-chloro-3-(2-thienoyl)benzenesulphonyl chloride.