Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si](CC)(CC)CC)[CH2:16]I)=[CH:11][C:10]=1[NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:31]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)P(N(C)C)(N(C)C)=O.C(OCC)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:18])[CH2:16][NH2:31])=[CH:11][C:10]=1[NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC[Si](CC)(CC)O[C@@H](CI)c1ccc(OCc2ccccc2)c(NS(C)(=O)=O)c1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CS(=O)(=O)Nc1cc([C@@H](O)CN)ccc1OCc1ccccc1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
A mixture of N-[2-benzyloxy-5-(2-iodo-(1R)-1-[(triethylsilyl)oxy]-ethyl)-phenyl}-methanesulfonamide (EP 0 659 737) (4.48 g, 8 mmol) and sodium azide (0.65 g, 10 mmol) in 100 mL of hexamethylphosphoramide was stirred at 60° C. overnight. After cooling to room temperature the mixture was diluted with diethyl ether, washed with water, dried over Na2SO4 and concentrated under reduced pressure. The residue was dissolved in 200 mL of THF/H2O (10:1) and triphenylphosphine (2.62 g, 10 mmol) was added. After overnight stirring at room temperature, the solvents were removed and the residue was partitioned between ethyl acetate and water. The organic layers were combined and dried over MgSO4 and concentrated. The residue was redissolved in 100 mL of THF and tetrabutylammonium fluoride (10 mL, 1 M solution in THF) was added. The reaction was stirred for 2 hours then the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel using triethylamine-methanol-methylene chloride (1:1:3) to give the title compound as a white solid; MS (ES) m/z: 337.4 (M++H).
Reaction SMILES: C([C:4]1([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:9][CH2:8][CH2:7][CH2:6][C:5]1=[O:10])(=O)C.OO.S(=O)(=O)(O)[OH:21]>C(O)(C)(C)C>[CH2:16]([O:15][C:13]([CH2:12][CH2:11][C:4]1([C:5]([OH:10])=[O:21])[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:14])[CH3:17]
Reactant: CCOC(=O)CCC1(C(C)=O)CCCCC1=O
Reactant: O=S(=O)(O)O
Agent: OO
Solvent: CC(C)(C)O
Product: CCOC(=O)CCC1(C(=O)O)CCCC1
Reaction time: 24 h

Procedure:
To a solution of 2-acetyl-2-[2-(ethoxycarbonyl)ethyl]-cyclohexanone (see Preparation 4) (40 g, 0.16 mol) in tert-butanol (85 ml) was added, dropwise, a 30% aqueous solution of hydrogen peroxide (21.7 ml, 0.19 mol) and concentrated sulfuric acid (0.25 ml, 98% w/w) at room temperature. The mixture was further stirred for 24 hours, partitioned between dichloromethane (100 ml) and distilled water (100 ml) and the layers separated. The dichloromethane layer was washed with 5% aqueous sodium sulphite solution, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a yellow oil, (34.35 g). Purification of this material by chromatography on silica by eluting with ethyl acetate/hexane (1:2 changing to 1:1), followed by neat ethyl acetate in the latter stages, gave, after combination and evaporation of appropriate fractions, the title compound as a yellow oil, (22.96 g, 67%). RF. 0.28 (silica, ethyl acetate/hexane, 1:1). 1H-NMR (300 MHz, CDCl3): =1.31 (t, 3H), 1.47-1.62 (m, 2H), 1.62-1.82 (m, 4H), 1.92-2.08 (m, 2H), 2.10-2.27 (m, 2H), 2.32-2.46 (m, 2H), 4.19 (q, 2H) ppm. 13C-NMR (75.5 MHz, CDCl3) 14.26, 25.15, 31.21, 33.56, 36.15, 53.21, 60.49, 173.38, 183.52 ppm.
Reaction SMILES: [C:1]12[C:14](=[O:15])[O:13][C:11](=[O:12])[C:2]=1[CH2:3][CH2:4][C:5]1[C:10]2=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:16][C:17]([CH3:22])([CH2:20][NH2:21])[CH2:18][OH:19].O>C1(C)C=CC=CC=1>[OH:19][CH2:18][C:17]([CH3:22])([CH3:16])[CH2:20][N:21]=[C:14]([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][C:2]=1[C:11]([OH:13])=[O:12])[OH:15]
Reactant: CC(C)(CN)CO
Reactant: O=C1OC(=O)C2=C1CCc1ccccc12
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(CO)CN=C(O)C1=C(C(=O)O)CCc2ccccc21

Procedure:
20.0 g (0.1 mol) of 3,4-dihydronaphthalene-1,2-dicarboxylic acid anhydride and 10.3 g (0.1 mol) of 2,2-dimethyl-3-aminopropanol are dissolved in 60 ml of toluene and the solution is refluxed for 2 hours, the water formed being separated off by means of a water separator. After the reaction has ended, the reaction mixture is concentrated to dryness in vacuo at 60° C. The residue is recrystallised from ethanol. This yields 25.1 g (87.9% of theory) of N-(3'-hydroxy-2',2'-dimethylpropyl)-3,4-dihydronaphthalene-1,2-dicarboxylic acid imide.
Reaction SMILES: [C:1]([O:5][C:6](=[O:31])[CH2:7][C@@H:8]([C:16](N1[C@H](C)[C@H](C2C=CC=CC=2)OC1=O)=[O:17])[CH2:9][C@H:10]([CH3:15])[CH2:11][CH2:12][CH2:13][CH3:14])([CH3:4])([CH3:3])[CH3:2].[OH:32]O>C1COCC1.O>[C:1]([O:5][C:6](=[O:31])[CH2:7][C@H:8]([CH2:9][C@H:10]([CH3:15])[CH2:11][CH2:12][CH2:13][CH3:14])[C:16]([OH:17])=[O:32])([CH3:2])([CH3:3])[CH3:4]
Reactant: OO
Reactant: CCCC[C@@H](C)C[C@@H](CC(=O)OC(C)(C)C)C(=O)N1C(=O)O[C@@H](c2ccccc2)[C@H]1C
Solvent: C1CCOC1
Solvent: O
Product: CCCC[C@@H](C)C[C@@H](CC(=O)OC(C)(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of ester 138 (2.65 g, 6.14 mmol) in 20 mL THF at 0° C. was added a precooled (0° C.) solution of LiOH monohydrate (1.0 g, 23.8 mmol) and hydrogen peroxide (30 wt % aqueous soln, 5.0 mL) in 10 mL H2O. The mixture was stirred vigorously for 90 minutes, then warmed to ambient temperature and stirred 90 minutes. The reaction was quenched at 0° C. by addition of 100 mL 10% NaHSO3 (aq), then extracted with Et2O. The phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated. The crude acid 139 was used without purification.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:6]=[C:5]([F:18])[C:3]=1[NH2:4].[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][C:21]=1[N:30]=[C:31]=[O:32]>C1COCC1>[F:18][C:5]1[CH:6]=[C:7]([B:9]2[O:13][C:12]([CH3:14])([CH3:15])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:8]=[C:2]([F:1])[C:3]=1[NH:4][C:31]([NH:30][C:21]1[CH:22]=[C:23]([C:26]([F:27])([F:29])[F:28])[CH:24]=[CH:25][C:20]=1[F:19])=[O:32]
Reactant: O=C=Nc1cc(C(F)(F)F)ccc1F
Reactant: CC1(C)OB(c2cc(F)c(N)c(F)c2)OC1(C)C
Solvent: C1CCOC1
Product: CC1(C)OB(c2cc(F)c(NC(=O)Nc3cc(C(F)(F)F)ccc3F)c(F)c2)OC1(C)C
Reaction time: 8 h
Yield: 71 %

Procedure:
To a solution of 2,6-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.300 g, 1.18 mmol) in THF (2 mL) was added 1-fluoro-2-isocyanato-4-(trifluoromethyl)benzene (0.314 g, 1.53 mmol). The reaction was stirred at 45 C overnight. Solid product was present in the reaction vessel. Product was further precipitated by the addition of 1:3 ether/hexanes. The solids were collected by filtration, dried under hi vacuum and found to be clean title compound in 71% yield. 1H-NMR (DMSO-d6) δ 7.03 (dd, J=6.6, 1.8 Hz, 2H), 5.76 (s, 2H), 1.26 (s, 12H); MS [M+H]+=461.2, LCMS RT=4.11 min
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][O:4][CH:3]=1.[CH2:7]([OH:10])[C:8]#[CH:9]>[Cu]I>[O:4]1[CH:5]=[CH:6][C:2]([C:9]#[C:8][CH2:7][OH:10])=[CH:3]1
Reactant: C#CCO
Reactant: Brc1ccoc1
Agent: [Cu]I
Product: OCC#Cc1ccoc1

Procedure:
To a mixture of 3-bromofuran (10 g, 0.068 mol) and propargyl alcohol (4.3 ml, 0.074 mol) in 200 ml of TEA was added under argon, CuI (0.26 g, 1.4 mmol) and [(C6H5)3P]2PdCl2 (1.05 g, 1.4 mmol) and the mixture was stirred at 0° C. for 2 hours and at room temperature for 72 hours. The reaction mixture was cooled, decanted, and the solid was washed with TEA. The combined TEA solution was concentrated in vacuo and the residue was distilled (Kugelrohr distillation) to afford 1.48 g (17.8%) of 3-(3-furyl-2-propynyl alcohol.
Reaction SMILES: [OH:1]O.[Cl:3][C:4]1[C:5]([O:19][CH2:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])=[N:6][CH:7]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:9]=1>CO>[Cl:3][C:4]1[CH:9]=[C:8]([OH:1])[CH:7]=[N:6][C:5]=1[O:19][CH2:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23]
Reactant: OO
Reactant: CC1(C)OB(c2cnc(OCC(F)(F)C(F)F)c(Cl)c2)OC1(C)C
Solvent: CO
Product: Oc1cnc(OCC(F)(F)C(F)F)c(Cl)c1
Temperature: 25 °C
Yield: 81.8 %

Procedure:
Hydrogen peroxide solution (30% aq. solution, 30.2 mL, 0.26 mol) was added to a solution of 3-chloro-2-(2,2,3,3-tetrafluoropropoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Preparation 49, 81.0 g, 0.22 mol) in methanol (500 mL) at 0° C. and the reaction was allowed to warm up to room temperature for 4 hours. The reaction mixture was quenched with aqueous sodium thiosulphate (10%, 100 mL) and the methanol removed in vacuo. The resulting mixture was extracted with EtOAc (2×250 mL). The combined organics swere dried over magnesium sulfate, filtered and evaporated to yield a yellow oil, which was purified by silica gel chromatogrpahy eluting with 10% EtOAc in heptane to afford the title compound as a viscous colourless oil (46.7 g, 82%).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]([NH:6][C:7](=[O:9])[CH3:8])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:23]1[C:28]([C:29]2[N:34]=[C:33]([CH3:35])[N:32]=[C:31]([N:36]([CH2:46][C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)[CH2:37][C:38]3[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=3)[N:30]=2)=[CH:27][C:26]([CH2:55][N:56]2[CH2:61][CH2:60][N:59]([S:62]([CH3:65])(=[O:64])=[O:63])[CH2:58][CH2:57]2)=[CH:25][N:24]=1>C1COCC1>[CH3:54][O:53][C:50]1[CH:49]=[CH:48][C:47]([CH2:46][N:36]([CH2:37][C:38]2[CH:39]=[CH:40][C:41]([O:44][CH3:45])=[CH:42][CH:43]=2)[C:31]2[N:32]=[C:33]([CH3:35])[N:34]=[C:29]([C:28]3[C:23]([NH:1][C:2]4[CH:3]=[CH:4][C:5]([NH:6][C:7](=[O:9])[CH3:8])=[CH:10][CH:11]=4)=[N:24][CH:25]=[C:26]([CH2:55][N:56]4[CH2:61][CH2:60][N:59]([S:62]([CH3:65])(=[O:64])=[O:63])[CH2:58][CH2:57]4)[CH:27]=3)[N:30]=2)=[CH:52][CH:51]=1
Reactant: CC(=O)Nc1ccc(N)cc1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(CN4CCN(S(C)(=O)=O)CC4)cnc3F)n2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(CN4CCN(S(C)(=O)=O)CC4)cnc3Nc3ccc(NC(C)=O)cc3)n2)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 57.8 %

Procedure:
A solution of 4′-aminoacetanilide (0.097 g, 0.643 mmol) in THF (5 mL) was cooled to 0° C. under N2. Lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (Aldrich) (0.313 mL, 1.608 mmol) was added and the mixture was stirred at 0° C. for 30 min before 4-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.200 g, 0.322 mmol) was added. The resulting mixture was stirred at 0° C. for 10 min, and then the ice bath was removed and stirring was continued for 2 h. The reaction was quenched with sat. NH4Cl. The resulting mixture was partitioned between pH 7 buffer (1 M TRIS-HCl) and CHCl3. The aqueous layer was extracted with CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 3% MeOH and 12% EtOAc in DCM) to give the product as a yellow solid (0.140 g). m/z (ESI, +ve ion) 752.0 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 11.82 (s, 1H); 8.72 (s, 1H); 8.24 (s, 1H); 7.54 (d, J=8.48 Hz, 2H); 7.40 (d, J=8.62 Hz, 2H); 7.22 (d, J=7.75 Hz, 4H); 7.07 (br. s., 1H); 6.87 (dd, J=8.18, 4.09 Hz, 4H); 4.85 (d, J=4.68 Hz, 4H); 3.81 (d, J=3.95 Hz, 6H); 3.51 (s, 2H); 3.19 (br. s., 4H); 2.71 (s, 3H); 2.60 (s, 3H); 2.44-2.58 (m, 4H); 2.18 (s, 3H).
Reaction SMILES: C([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:51])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:50])[CH2:12][CH2:13][C@@:14]3([C:30]([CH:32]4[CH2:37][CH2:36][C:35]([CH2:43][C:44]5[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=5)([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:34][CH2:33]4)=[O:31])[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]32)[C:6]1([CH3:53])[CH3:52])(=O)C.C1COCC1.[OH-].[Na+]>CO>[CH2:43]([C:35]1([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:36][CH2:37][CH:32]([C:30]([C@:14]23[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]2[C@@H:16]2[C@@:11]([CH3:50])([CH2:12][CH2:13]3)[C@@:10]3([CH3:51])[C@@H:19]([C@:20]4([CH3:23])[C@@H:7]([CH2:8][CH2:9]3)[C:6]([CH3:52])([CH3:53])[C@@H:5]([OH:4])[CH2:22][CH2:21]4)[CH2:18][CH2:17]2)=[O:31])[CH2:33][CH2:34]1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)C3CCC(Cc4ccccc4)(C(=O)OCC)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(C)=O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)C3CCC(Cc4ccccc4)(C(=O)OCC)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 25 °C
Reaction time: 6 h
Yield: 53.1 %

Procedure:
Ethyl 4-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetoxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carbonyl)-1-benzylcyclohexanecarboxylate (Example 55, 0.9 g) was taken in MeOH:THF (8:8 ml) and cooled the contents to 0° C. then sodium hydroxide (0.28 g in 4 ml water) was added and stirred for about 6 hours at room temperature. Completion of the reaction was monitored by TLC. The reaction mixture was evaporated under reduced pressure and the residue was taken in water, extracted with DCM, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 5% methanol in DCM as eluent to furnish the title compound (0.45 g) as a white solid. 1H NMR (300 MHz, CDCl3): 0.57-0.97 (m, 19H); 1.18-1.21 (m, 8H); 1.25-1.41 (m, 12H); 1.49-1.62 (m, 8H); 1.65-1.82 (m, 10H); 1.85-1.98 (m, 4H); 2.56-2.69 (m, 2H); 3.29-3.38 (m, 1H); 3.89-3.90 (m, 1H); 4.12-4.23 (m, 2H) 4.56 (s, 1H); 4.71 (s, 1H); 7.03-7.05 (m, 2H); 7.23-7.25 (m, 3H); MASS: 685 (100%).
Reaction SMILES: [CH2:1]([CH:8]1[C:12](=O)O[NH:10][N:9]1[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([Sn:17]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:22][CH2:23][CH2:24][CH3:25])[CH2:18][CH2:19][CH2:20][CH3:21])#C>C1(C)C(C)=CC=CC=1>[CH2:1]([C:8]1[N:9]([CH3:14])[N:10]=[C:15]([Sn:17]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:22][CH2:23][CH2:24][CH3:25])[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#C[Sn](CCCC)(CCCC)CCCC
Reactant: CN1NOC(=O)C1Cc1ccccc1
Solvent: Cc1ccccc1C
Product: CCCC[Sn](CCCC)(CCCC)c1cc(Cc2ccccc2)n(C)n1
Temperature: 140 °C

Procedure:
4-Benzyl-3-methyl-1,2,3-oxadiazol-5-one (0.600 g) and ethynyltri-n-butyltin (2.5 ml) were dissolved in xylene (10 ml) and heated to 140° C. under argon for 16 h. The solvent was then evaporated and the residue was chromatographed over silica gel. Elution with a gradient of 0 to 10% acetone/toluene gave the product as a yellow oil (0.189 g); dH (CDCl3) 0.8-1.7 (27H, m), 3.77 (3H, s), 4.00 (2H, s), 6.09 (1H, s), 7.10-7.40 (5H, m).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-])=O)=[C:6]([O:13][CH2:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:5]=1>CO.[Cl-].[NH4+].C(OCC)(=O)C.[Zn]>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([O:13][CH2:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:5]=1
Reactant: COC(=O)c1ccc([N+](=O)[O-])c(OCc2cccnc2)c1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(N)c(OCc2cccnc2)c1
Reaction time: 12 h
Yield: 97 %

Procedure:
To a stirred, cooled (about 0° C.) solution of 4-nitro-3-(pyridin-3-ylmethoxy)-benzoic acid methyl ester (288 mg, 1.0 mmol) in methanol (2 mL) and saturated aqueous ammonium chloride (1 mL) was added zinc dust (131 mg, 2.0 mmol). After stirring for 12 hours, the reaction was diluted with 30 mL of ethyl acetate and washed with 30 mL of 10% aqueous sodium carbonate (2×30 mL), brine (1×30 mL), then dried (MgSO4), and filtered. The filtered solution was concentrated under reduced pressure to yield the desired product as a yellow solid (97% yield). 1H-NMR (400 MHz, CDCl3) δ8.78 (s, 1H), 8.61 (d, 1H, 7.79 (d, 1H), 7.59 (m, 2H), 7.39 (m, 1H), 6.71 (d, 1H), 5.18 (s, 2H), 4.28 (br s, 2H), 3.85 (s, 3H).
Reaction SMILES: [CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([OH:20])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[C:36]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])(=[O:39])[NH:37][NH2:38]>O1CCCC1>[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([NH:38][NH:37][C:36]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)NN
Reactant: O=C(O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Agent: CC(C)COC(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 111.4 %

Procedure:
To a solution of the carboxylic acid (6b, 371 mg, 1.34 mmol) of Example 9 or 16 in tetrahydrofuran (7 mL) were added triethylamine (0.227 mL) and isobutyl chloroformate (218 μl) under ice-cooling, followed by stirring at 0° C. for 15 minutes. To the reaction solution was added t-butyl carbazate (245 mg) at 0° C., followed by stirring at room temperature for 1.5 hours, and then concentrating under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1-0/1) to afford 583 mg of the title compound (yield 98%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[NH:5][C:6]1[CH:11]=[C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=2)[N:9]=[CH:8][N:7]=1.Br[CH2:24][CH:25]1[O:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[O:27]1[CH2:26][CH:25]1[CH2:24][O:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[NH:5][C:6]1[CH:11]=[C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=2)[N:9]=[CH:8][N:7]=1
Reactant: Cc1cccc(Nc2cc(Nc3cccc(O)c3)ncn2)c1
Reactant: BrCC1CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: Cc1cccc(Nc2cc(Nc3cccc(OCC4CO4)c3)ncn2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 38 %

Procedure:
A mixture of 4-[3'-hydroxyanilino]6-(3'-methylanilino)pyrimidine (1 g), 1-bromo-2,3-epoxypropane (0.44 ml) and potassium carbonate (0.95 g) in DMSO (12 ml) was stirred at ambient temperature overnight. The reaction mixture was diluted with water and extracted with methylene chloride. The organic layer was washed with water, dried (MgSO4) and evaporated to give 4-[3'-(2,3-epoxypropoxy)anilino]6-(3'-methylanilino)pyrimidine in 38% yield, m.p. 143°-145° C.;
Reaction SMILES: I[C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35])CCC>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[CH3:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccc1C
Reactant: O=C(c1ccc(I)cc1)N1Cc2cccn2Cc2ccccc21
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Cc1ccccc1-c1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cc1
Yield: 54.7 %

Procedure:
A mixture of 2.0 g of 10,11-dihydro-10-(4-iodobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, 3.0 g of 2-(tributylstannyl)toluene and 200 mg of tetrakis(triphenylphosphine)palladium(O) in 200 ml of toluene is refluxed for 16 hours. The reaction mixture is evaporated in vacuo to a residue which is purified by column chromatography on silica gel by elution with 30% ethyl acetate-hexane to give 1.0 g of the desired product as a solid. Mass spectrum: M+H:379.
Reaction SMILES: C(N(C1C=CC([C:14]2[N:15]=[C:16]3[N:20]([CH:21]=2)[CH2:19][CH2:18][S:17]3)=CC=1)C(=O)C)CC.ClC(OCC)=O.C1C2C(CCCC2)CCC1.[S].[N:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(Cl)Cl>[N:39]1[CH:44]=[CH:43][C:42]([C:21]2[N:20]3[C:16]([S:17][CH2:18][CH2:19]3)=[N:15][CH:14]=2)=[CH:41][CH:40]=1
Reactant: CCCN(C(C)=O)c1ccc(-c2cn3c(n2)SCC3)cc1
Reactant: c1ccncc1
Agent: CCOC(=O)Cl
Agent: [S]
Solvent: ClCCl
Solvent: C1CCC2CCCCC2C1
Product: c1cc(-c2cnc3n2CCS3)ccn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The N-propylacetamido Formula (III) compound (0.60 g, 0.002 mole), prepared as described above in part a, was then suspended in CH2Cl2 (10 ml) and dry pyridine (0.47 ml, 0.006 mole) was added. The suspension was heated to aid in dissolving the solid, then cooled to ice-bath temperature. Ethyl chloroformate (0.72 ml, 0.648 g, 0.006 mole) in 2 ml CH2Cl2 was added dropwise to this mixture over a one hour period. The solution was stirred at room temperature for one hour and then heated at reflux for 10 min. The reaction was then cooled to 10° C. and an additional equivalent of pyridine (161 μl) and ethyl chloroformate (240 μl) was added. After heating at reflux for 10 min., the reaction was left to stir at room temperature overnight. The reaction was then washed with water (3×100 ml) and the organic layer stripped then decalin (5 ml) and sulfur (0.063 g, 0.002 mole) were added and the mixture was heated to 170° C. This temperature was maintained for one hour. The reaction was then diluted with CH2Cl2 and extracted with a 12% HCl solution. The acidic layer was basified with solid K2CO3 and then extracted with CH2Cl2. After treating with brine and MgSO4, the CH2Cl2 was removed, and the residue was flash chromatographed (0.10% MeOH/100-90% CH2Cl2) to give 0.2 g of a (Formula (I) compound), 6-4-(N-propylacetamido)phenyl)-5-(4-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole (TLC: Rf =0.22 5% MeOH/95% CH2Cl2.
Reaction SMILES: [OH:1][C:2]1[C:7]2[CH:8]=[C:9]([CH3:11])[O:10][C:6]=2[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=1.[CH:17]([N:30]1[CH2:33][CH:32](OS(C)(=O)=O)[CH2:31]1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[C:18]1([CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:30]2[CH2:33][CH:32]([O:1][C:2]3[C:7]4[CH:8]=[C:9]([CH3:11])[O:10][C:6]=4[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=3)[CH2:31]2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CCOC(=O)c1cc(O)c2cc(C)oc2c1
Reactant: CS(=O)(=O)OC1CN(C(c2ccccc2)c2ccccc2)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cc(OC2CN(C(c3ccccc3)c3ccccc3)C2)c2cc(C)oc2c1
Temperature: 100 °C
Reaction time: 4 h
Yield: 63.1 %

Procedure:
A mixture of ethyl 4-hydroxy-2-methyl-1-benzofuran-6-carboxylate (252c) (1.70 g, 7.72 mmol), 1-(diphenylmethyl)azetidin-3-yl methanesulfonate (193a) (2.95 g, 9.29 mmol) and Cs2CO3 (6.29 g, 19.3 mmol) in DMF (10 mL) was stirred for 4 hours at 100° C. The reaction was cooled to room temperature, diluted with EtOAc and washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The product was purified via gradient silica gel chromatography using EtOAc/Hexanes (10/90 to 40/60) to give the desired compound (2.15 g, 63%) as a white solid after evaporation of the solvent. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.32-1.49 (m, 3 H) 2.42-2.57 (m, 3 H) 3.10-3.29 (m, 2 H) 3.75-3.94 (m, 2 H) 4.27-4.42 (m, 2 H) 4.43-4.52 (m, 1 H) 4.91-5.10 (m, 1 H) 6.50 (s, 1 H) 7.05 (s, 1 H) 7.15-7.25 (m, 2 H) 7.24-7.35 (m, 4 H) 7.39-7.54 (m, 4 H) 7.74 (s, 1 H); MS (ESI, pos): 442.