Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][CH:4]=[C:3]([O:10][C:11]2[C:16]([Cl:17])=[CH:15][C:14]([Cl:18])=[CH:13][C:12]=2Cl)[CH:2]=1.C1C([N+]([O-])=O)=CC=C(OC2C=CC(C(F)(F)F)=CC=2[N+]([O-])=O)C=1.ClC1C=C(C(F)(F)F)C=CC=1OC1C=CC([N+]([O-])=O)=C(C=1)C([O-])=O.[Na+].ClC1C=C(C(F)(F)F)C=CC=1OC1C=CC([N+]([O-])=O)=C(OCC)C=1.ClC1C=C(C(F)(F)F)C=CC=1OC1C=CC([N+]([O-])=O)=C(C=1)C(OC(C(OCC)=O)C)=O.ClC1C=C(C(F)(F)F)C=CC=1OC1C=CC([N+]([O-])=O)=C(C=1)C(NS(C)(=O)=O)=O>>[CH:5]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:1][CH:2]=[C:3]([O:10][C:11]2[CH:12]=[CH:13][C:14]([Cl:18])=[CH:15][C:16]=2[Cl:17])[CH:4]=1
Reactant: O=[N+]([O-])c1ccc(Oc2c(Cl)cc(Cl)cc2Cl)cc1
Agent: CCOC(=O)C(C)OC(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Agent: CCOc1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Agent: CS(=O)(=O)NC(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Product: O=[N+]([O-])c1ccc(Oc2ccc(Cl)cc2Cl)cc1

Procedure:
2,4,6-trichloro-4'-nitrodiphenyl ether; 2,4-dichloro-6-fluoro-4'-nitrodiphenyl ether; 3methyl-4'-nitrodiphenyl ether; 3,5-dimethyl-5'-nitrodiphenyl ether; 2,4'-dinitro-4-(trifluoromethyl)diphenyl ether; 2,4-dichloro-3'-methoxy-4'-nitrodiphenyl ether; sodium 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitrobenzoate; 2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene; 1-(carboethoxy)ethyl 5-[2-chloro-4-(trifluoromethyl)-phenoxy]-2-nitrobenzoate; 5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-(methylsulphonyl)-2-nitrobenzamide;
Reaction SMILES: CN(C)C=O.[H-].[Na+].[C:8]([O:14][CH2:15][CH3:16])(=[O:13])[CH2:9][C:10]([CH3:12])=[O:11].[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[CH2:21]Cl>C1C=CC=CC=1>[C:10]([CH:9]([CH2:21][C:20]1[CH:23]=[CH:24][CH:25]=[C:18]([F:17])[CH:19]=1)[C:8]([O:14][CH2:15][CH3:16])=[O:13])(=[O:11])[CH3:12]
Reactant: Fc1cccc(CCl)c1
Reactant: CCOC(=O)CC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CCOC(=O)C(Cc1cccc(F)c1)C(C)=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 500 mL of 10% dimethylformamide in benzene was added 58.6% NaH (41 g, 1.0 mol) cooled in an ice bath was added ethyl acetoacetate (130 g, 1.0 mol) was added. The reaction was stirred at room temperature for 30 minutes, and m-fluorobenzyl chloride (145 g, 1.0 mol) was added. The reaction was heated to reflux for 3 hours and gave an NaCl precipitate which was then removed by filtration. The filtrated was poured into H2O, acidified with concentrated HCl and was extracted with a mixture of ether and benzene. The organic layer was washed with H2O, brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by distillation (112-119° C./25 mmHg) to give compound A (133 g, 56%).
Reaction SMILES: [CH3:1][C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][CH2:11][N:12]([C:13](=[O:51])[CH2:14][N:15]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[N:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:18](=[O:32])[CH:17]([CH2:33][C:34]4[C:42]5[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=5)[N:36](C(OC(C)(C)C)=O)[N:35]=4)[C:16]3=[O:50])[C:6]=2[CH:5]=[C:4]([CH3:52])[CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][C:2]1[C:7]2[CH2:8][CH2:9][CH2:10][CH2:11][N:12]([C:13](=[O:51])[CH2:14][N:15]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[N:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:18](=[O:32])[CH:17]([CH2:33][C:34]4[C:42]5[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=5)[NH:36][N:35]=4)[C:16]3=[O:50])[C:6]=2[CH:5]=[C:4]([CH3:52])[CH:3]=1
Reactant: Cc1cc(C)c2c(c1)N(C(=O)CN1C(=O)C(Cc3nn(C(=O)OC(C)(C)C)c4ccccc34)C(=O)N(c3ccccc3)c3ccccc31)CCCC2
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(C)c2c(c1)N(C(=O)CN1C(=O)C(Cc3n[nH]c4ccccc34)C(=O)N(c3ccccc3)c3ccccc31)CCCC2
Reaction time: 3 h
Yield: 12.8 %

Procedure:
A solution of tert-butyl 3-({1-[2-(6,8-dimethyl-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)-2-oxoethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl}methyl)-1H-indazole-1-carboxylate (64 mg) in methylene chloride (10 mL) was treated with trifluoroacetic acid (1 mL). The reaction was stirred for 3 hours then concentrated to dryness. The residue was chromatographed on silica gel (Hexane:Ethyl Acetate. The residue was triturated with Ethyl Ether and filtered to yield the title compound as an off-white solid (7 mg).
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH2:25]O)[CH:20]=3)[N:15]=2)=[CH:10][C:9]=1[C:27]([F:30])([F:29])[F:28].CCN(C(C)C)C(C)C.CS([Cl:44])(=O)=O.O>C(Cl)Cl>[Cl:44][CH2:25][C:21]1[CH:20]=[C:19]([C:16]2[N:15]=[C:14]([C:11]3[CH:12]=[CH:13][C:8]([N:3]4[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]4[CH3:1])=[C:9]([C:27]([F:30])([F:28])[F:29])[CH:10]=3)[O:18][N:17]=2)[CH:24]=[CH:23][N:22]=1
Reactant: CC1CCCCN1c1ccc(-c2nc(-c3ccnc(CO)c3)no2)cc1C(F)(F)F
Reactant: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: CC1CCCCN1c1ccc(-c2nc(-c3ccnc(CCl)c3)no2)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.4 %

Procedure:
To a solution of (4-(5-(4-(2-methylpiperidin-1-yl)-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)methanol (0.125 g; 0.30 mmol) and DIEA (0.10 mL; 0.60 mmol) in DCM (2.5 mL) was added methanesulfonyl chloride (0.026 mL; 0.33 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. Water was added to the reaction mixture and the mixture poured through a hydrophobic frit. The solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (100% iso-hexane to 100% EtOAc) to afford the title product (0.129 g, 98%). 1H NMR (CDCl3, 400 MHz) δ 8.77 (1 H, dd, J=5.1, 0.9 Hz), 8.51 (1 H, d, J=2.1 Hz), 8.34 (1H, dd, J=8.4, 2.1 Hz), 8.23 (1 H, s), 7.99 (1 H, dd, J=5.1, 1.6 Hz), 7.56 (1 H, d, J=8.4 Hz), 4.78 (2 H, s), 3.12-3.03 (2 H, m), 2.59 (1 H, td, J=11.0, 3.1 Hz), 1.86-1.62 (4 H, m), 1.53-1.38 (2 H, m), 0.86 (3 H, d, J=6.2 Hz).
Reaction SMILES: C([Si](C)(C)[O:6][CH2:7][C:8]([N:11]1[C:19]2[C:18]([F:20])=[CH:17][N:16]=[CH:15][C:14]=2[C:13]([C:21]([C:23]2[CH:24]=[C:25]([NH:29][C:30](=[O:42])[CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=3)[CH:26]=[N:27][CH:28]=2)=[O:22])=[CH:12]1)([CH3:10])[CH3:9])(C)(C)C>C1COCC1>[F:20][C:18]1[C:19]2[N:11]([C:8]([CH3:10])([CH3:9])[CH2:7][OH:6])[CH:12]=[C:13]([C:21]([C:23]3[CH:24]=[C:25]([NH:29][C:30](=[O:42])[CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:41])[F:40])[CH:33]=4)[CH:26]=[N:27][CH:28]=3)=[O:22])[C:14]=2[CH:15]=[N:16][CH:17]=1
Reactant: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(NC(=O)Cc3cccc(C(F)(F)F)c3)c2)c2cncc(F)c21
Solvent: C1CCOC1
Product: CC(C)(CO)n1cc(C(=O)c2cncc(NC(=O)Cc3cccc(C(F)(F)F)c3)c2)c2cncc(F)c21
Temperature: 25 °C
Reaction time: 2 h
Yield: 86 %

Procedure:
To a solution of N-(5-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-7-fluoro-1H-pyrrolo[3,2-c]pyridine-3-carbonyl}-pyridin-3-yl)-2-(3-trifluoromethyl-phenyl)-acetamide (Preparation 3, 40 mg, 63 μmol) in THF (5 mL) 4M dioxane-HCl (0.5 mL) was added and stirred at room temperature for 2 hours. The reaction was evaporated in vacuo and triturated with pentane-ether to afford the title compound as a yellow solid in 86% yield, 28 mg.
Reaction SMILES: C([O:3][C:4](=[O:17])[CH:5]([C:7]1[CH:8]=[CH:9][C:10]2[O:14][C:13](=[S:15])[NH:12][C:11]=2[CH:16]=1)[CH3:6])C.[OH-].[Na+].C(O)(=O)C>CCO.O>[S:15]=[C:13]1[NH:12][C:11]2[CH:16]=[C:7]([CH:5]([CH3:6])[C:4]([OH:17])=[O:3])[CH:8]=[CH:9][C:10]=2[O:14]1
Reactant: CCOC(=O)C(C)c1ccc2oc(=S)[nH]c2c1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCO
Solvent: O
Product: CC(C(=O)O)c1ccc2oc(=S)[nH]c2c1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a stirred solution of 2-(2-Thioxo-2,3-dihydro-benzooxazol-5-yl)-propionic acid ethyl ester (124 mg) in 90% aq. EtOH was added NaOH (102 mg) at room temperature. After stirred for 20 h at 45, the reaction mixture was cooled to room temperature, diluted with water. The resulting aqueous layer was acidified with acetic acid and then extracted with dichloromethane. The combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. (105 mg, 95.4%)
Reaction SMILES: Cl[C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([CH3:19])[C:3]=1[CH:20]=[O:21].[N-:22]=[N+]=[N-].[Na+]>CS(C)=O>[NH2:22][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([CH3:19])[C:3]=1[CH:20]=[O:21]
Reactant: Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(Cl)c1C=O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CS(C)=O
Product: Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1C=O

Procedure:
5-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-1H-pyrazole-4-carboxaldehyde (1.2 g) and sodium azide (0.3 g) were heated at 70° under a nitrogen atmosphere in dimethyl sulphoxide (15 ml) for 8 hours. The solvent was removed in vacuo and the residue redissolved in methanol (20 ml) containing piperidine (1 ml). This mixture was cooled to 15° while hydrogen sulphide gas was bubbled in slowly for 3 hours. The mixture was worked up to give 5-amino-1-(2,6-dichloro- 4-trifluoromethylphenyl)-3-methyl-1H-pyrazole-4-carboxaldehyde, m.p. 169°-172°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([OH:14])=O)[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH:63]1[CH2:68][CH2:67][NH:66][CH2:65][C:64]1=[O:69]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:66]1[CH2:67][CH2:68][NH:63][C:64](=[O:69])[CH2:65]1)=[O:14])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Reactant: O=C1CNCCN1
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(Nc1ncnc2cc(C(=O)N3CCNC(=O)C3)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and piperazinone in DMSO at ambient temperature.
Reaction SMILES: [CH:1]1([C:7]2[C:8]3[CH:31]=[CH:30][C:29]([C:32]([O:34][CH3:35])=[O:33])=[CH:28][C:9]=3[N:10]3[C:16]=2[C:15]2[CH:17]=[CH:18][C:19]([O:21][CH:22]4[CH2:27][CH2:26][CH2:25][NH:24][CH2:23]4)=[CH:20][C:14]=2[O:13][CH2:12][CH2:11]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:36][S:37](Cl)(=[O:39])=[O:38].C1(C)C=CC=CC=1>N1C=CC=CC=1>[CH:1]1([C:7]2[C:8]3[CH:31]=[CH:30][C:29]([C:32]([O:34][CH3:35])=[O:33])=[CH:28][C:9]=3[N:10]3[C:16]=2[C:15]2[CH:17]=[CH:18][C:19]([O:21][CH:22]4[CH2:27][CH2:26][CH2:25][N:24]([S:37]([CH3:36])(=[O:39])=[O:38])[CH2:23]4)=[CH:20][C:14]=2[O:13][CH2:12][CH2:11]3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCOc1cc(OC2CCCNC2)ccc1-3
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCOc1cc(OC2CCCN(S(C)(=O)=O)C2)ccc1-3
Temperature: 0 °C
Reaction time: 2 h
Yield: 93.5 %

Procedure:
To a solution of methyl 12-cyclohexyl-3-(piperidin-3-yloxy)-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylate (43 mg, 0.091 mmol) in pyridine (0.5 ml) was added dropwise methanesulfonyl chloride (8.5 μl, 0.11 mmol), and the mixture was stirred at 0° C. for 2 hr. Toluene was added to the reaction mixture and the solvent was evaporated under reduced pressure. Hexane and ethyl acetate were added to the obtained residue, and the precipitate was collected by filtration, washed with hexane, and dried in vacuo to give methyl 12-cyclohexyl-3-(1-methanesulfonylpiperidin-3-yloxy)-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylate (47 mg, yield 94%).
Reaction SMILES: Cl[O:2][N:3]=[CH:4][C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[CH:6]=1.C([O-])([O-])=O.[K+].[K+].[O:19]1[CH2:24][CH2:23][C:22](=[N:25][NH:26][C:27](=[O:37])[C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[C:29]=2[CH3:36])[CH2:21][CH2:20]1.O>C(Cl)(Cl)Cl.C(Cl)Cl>[CH3:12][C:7]1[CH:6]=[C:5]([C:4]2[N:25]([NH:26][C:27](=[O:37])[C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[C:29]=3[CH3:36])[C:22]3([CH2:21][CH2:20][O:19][CH2:24][CH2:23]3)[O:2][N:3]=2)[CH:10]=[C:9]([CH3:11])[CH:8]=1
Reactant: Cc1cc(C)cc(C=NOCl)c1
Reactant: COc1cccc(C(=O)NN=C2CCOCC2)c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: O
Product: COc1cccc(C(=O)NN2C(c3cc(C)cc(C)c3)=NOC23CCOCC3)c1C
Temperature: 57.5 °C
Reaction time: 8 h
Yield: 44 %

Procedure:
3,5-dimethyl-benzaldehyde chlorooxime (1.84 g, 4 mmol) was dissolved in 30 μL of CHCl3 in a round bottom flask. An aqueous solution of K2CO3 (25 mL, 0.166 g/mL) was added, followed by 1.05 g of 3-methoxy-2-methyl-benzoic acid (tetrahydro-pyran-4-ylidene)-hydrazide. The reaction was stirred overnight at 55-60° C. Water and CH2Cl2 (50 mL) were added, and the mixture was shaken in a separatory funnel. The aqueous phase was removed and extracted once with CHCl3 (25 mL). The organic phases were combined, washed once with dilute K2CO3, and dried over MgSO4. The solvent was removed in vacuo to yield 2.5 g of crude product. This material was triturated twice with 10% ether in hexane and then once with 25% ether in hexane. The solids were collected and filtered, yielding 720 mg of N-[3-(3,5-dimethyl-phenyl)-1,8-dioxa-2,4-diaza-spiro[4.5]dec-2-en-4-yl]-3-methoxy-2-methyl-benzamide at 80% purity and a 49% yield. 1H NMR (300 MHz, CDCl3) δ (ppm): 8.5 (s, 1H [NH]), 7.4 (s, 2H), 7.1 (m, 1H), 7.1 (s, 1H), 6.9 (d, 1H), 6.65 (d, 1H), 3.9 (m, 4H), 3.8 (s, 3H), 2.4 (m, 4H), 2.35 (s, 6H), 2.05 (s, 3H).
Reaction SMILES: [CH2:1]([O:3][Si:4]([C:11]12[CH2:17][CH:14]([CH2:15][CH2:16]1)[CH:13]=[CH:12]2)([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])[CH3:2].C([SiH]([CH2:23][CH3:24])CC)C.[CH2:25](O)[CH3:26]>ClCCl.C1COCC1.C1(C)C=CC=CC=1>[CH2:25]([C:11]12[CH2:17][CH:14]([CH2:15][CH2:16]1)[CH:13]=[CH:12]2)[CH2:26][CH2:23][CH3:24].[CH2:6]([O:5][Si:4]([C:11]12[CH2:17][CH:14]([CH2:15][CH2:16]1)[CH:13]=[CH:12]2)([O:8][CH2:9][CH3:10])[O:3][CH2:1][CH3:2])[CH3:7]
Reactant: CC[SiH](CC)CC
Reactant: CCO
Agent: CCO[Si](OCC)(OCC)C12C=CC(CC1)C2
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCCCC12C=CC(CC1)C2
Temperature: 80 °C

Procedure:
BuNB (25.22 g, 0.168 mol), Triethoxysilyl Norbornene (TESNB, CAS 18401-43-9) (4.78 g, 0.019 mol), triethyl silane (0.011 g, 9.32E-05 mol), ethanol (0.10 g, 224E-03 mol) and toluene (170.0 g) were combined in a 500 mL serum bottle and heated to 80° C. in an oil bath to form a solution. To this solution were injected Pdl 206 (0.018 g, 1.49E-05 mol) in the form of a concentrated solution in dichloromethane. After addition, the resulting mixture was maintained at 80° C. for 9 hours. The copolymer was precipitated by adding methanol drop wise into the vigorously stirred reaction mixture. The precipitated copolymer was collected by filtration and dried in an oven at 60° C. under vacuum. After drying, 20.58 g was obtained (69%). The molecular weight of the copolymer was determined by GPC in THF solvent (polystyrene standard) to be Mw=238,000 and Mn=96,000. The composition of the copolymer was determined by 1H-NMR to be (85/15) BuNB/TESNB copolymer. The refractive indices of this polymer were measured by prism coupling method and determined to be 1.5061 in TE mode and 1.5041 in TM mode at a wavelength of 633 nm. The Tg (based on thermomechanical analysis (TMA) measurement) of this polymer was 276° C. The dried copolymer was dissolved in sufficient toluene to result in a 30 wt % copolymer solution.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([OH:13])[CH:11]=2)[CH:6]=[N:5]1.Br[CH2:15][C:16]([O:18]CC)=[O:17]>CN(C=O)C.O>[CH3:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH2:15][C:16]([OH:18])=[O:17])[CH:11]=2)[CH:6]=[N:5]1
Reactant: CCOC(=O)CBr
Reactant: Cn1ncc2ccc(O)cc21
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1ncc2ccc(OCC(=O)O)cc21
Reaction time: 0.08 h
Yield: 72 %

Procedure:
To a solution of NaH (146 mg, 6.06 mmol) in DMF (3 mL) was added 1-methyl-1H-indazol-6-ol (300 mg, 2.02 mmol) at 25° C. After stirring for 5 minutes, ethyl 2-bromoacetate (406 mg, 2.43 mmol) was added and stirred for 16 h at 25° C. The mixture was then diluted with water (50 mL) and washed with ethyl acetate (2×20 mL). The water layer was then acidified by adding with 2N HCL until pH3 and then extracted with ethylacetate (2×20 ml). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated to give the crude product (300 mg, 63.4%) as colorless oil. It was used in next step without further purification. LCMS (m/z): 207.1 (M+1).
Reaction SMILES: O1CCCC1.[S:6]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([S:22][CH2:23][C:24]([F:27])([F:26])[F:25])[CH:16]=1)C#N.[F:28][C:29]([Si](C)(C)C)([F:31])[F:30].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>C(OCC)(=O)C.CCCCCC>[F:28][C:29]([F:31])([F:30])[S:6][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([S:22][CH2:23][C:24]([F:27])([F:25])[F:26])[CH:16]=1
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: Cc1ccc(OCCCCCSC#N)cc1SCC(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cc1ccc(OCCCCCSC(F)(F)F)cc1SCC(F)(F)F
Reaction time: 1 h
Yield: 77 %

Procedure:
To 100 ml of tetrahydrofuran were added 1.5 g (4.3 mmol) of 5-thiocyanatopentyl-{4-methyl-3-(2,2,2-trifluoroethylthio)phenyl}ether and 1.8 g (13 mmol) of trifluoromethyltrimethylsilane. Thereto was added, at 0° C., 5 ml (5.0 mmol) of a tetra-n-butylammonium fluoride-tetrahydrofuran (1 mol/liter) solution. A reaction was carried out for 1 hour. After confirmation of the completion of the reaction, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: a mixed solvent of n-hexane:ethyl acetate=10:1), to obtain 1.3 g (yield: 77%) of an intended product.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:10])[CH2:4][C:5]1([NH2:9])[CH2:8][O:7][CH2:6]1.C(N(CC)CC)C.[CH2:18]([O:20][C:21](=[O:26])[CH2:22][C:23](Cl)=[O:24])[CH3:19].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:18]([O:20][C:21](=[O:26])[CH2:22][C:23]([NH:9][C:5]1([CH2:4][C:3]([O:2][CH3:1])=[O:10])[CH2:8][O:7][CH2:6]1)=[O:24])[CH3:19]
Reactant: COC(=O)CC1(N)COC1
Reactant: CCOC(=O)CC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)CC(=O)NC1(CC(=O)OC)COC1
Temperature: 25 °C

Procedure:
(3-Amino-oxetan-3-yl)-acetic acid methyl ester (95 mg; 0.655 mmol) dissolved in CH2Cl2 (5 ml) and triethylamine (0.22 ml; 1.6 mmol) are cooled to −5° C. Chlorocarbonyl-acetic acid ethyl ester (0.1 ml; 0.79 mmol) is slowly added under stirring. The reaction mixture is warmed to room temperature, stirred for 20 minutes, poured on a saturated solution of NaHCO3 and extracted with CH2Cl2 three times. The organic phases are combined, dried over Na2SO4, filtered and evaporated to dryness. Chromatography (SiO2; Hexanes/acetone 4:1) yields the title compound as yellow resin. 1H-NMR (400 MHz; DMSO-d6): 8.93 (s, 1H); 4.54 (dd, 4H); 4.09 (q, 2H); 3.60 (s, 3H); 3.23 (s, 2H); 3.10 (s, 2H); 1.19 (t, 3H). MS (m/z) ES+: 260 (MH+)
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C[Al](C)C.[N:14]1([C:20]2[N:21]=[C:22]([CH2:33][C:34](OCC)=[O:35])[N:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:24](=[O:26])[CH:25]=2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>C1(C)C=CC=CC=1.O1CCCC1>[N:1]1([C:34](=[O:35])[CH2:33][C:22]2[N:23]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:24](=[O:26])[CH:25]=[C:20]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:21]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: CCOC(=O)Cc1nc(N2CCOCC2)cc(=O)n1-c1ccccc1
Reactant: c1ccc2c(c1)CCN2
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: O=C(Cc1nc(N2CCOCC2)cc(=O)n1-c1ccccc1)N1CCc2ccccc21
Temperature: 90 °C
Yield: 3.8 %

Procedure:
56 mg of indoline and 0.36 ml of 2M trimethyl aluminum in toluene are successively added to a solution of 65 mg of ethyl (4-morpholin-4-yl-6-oxo-1-phenyl-1,6-dihydropyrimidin-2-yl)acetate in 3 ml of tetrahydrofuran and 1.5 ml of toluene. The reaction mixture is heated at 90° C. for 4 hours and then concentrated under reduced pressure. The residue is purified twice by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (98/2, V/V) and then with ethyl acetate, so as to give 3 mg of 2-[2-(2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3-phenyl-3H-pyrimidin-4-one in the form of a solid, the characteristics of which are the following:
Reaction SMILES: P(Br)(Br)[Br:2].[CH2:5]([C:13]1[CH:20]=[CH:19][C:16]([CH2:17]O)=[CH:15][CH:14]=1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]>CCOCC>[CH2:5]([C:13]1[CH:20]=[CH:19][C:16]([CH2:17][Br:2])=[CH:15][CH:14]=1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: BrP(Br)Br
Reactant: CCCCCCCCc1ccc(CO)cc1
Solvent: CCOCC
Product: CCCCCCCCc1ccc(CBr)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 40 %

Procedure:
PBr3 (0.23 ml) was added drop wise to a stirred solution of the product of Step A (0.082 g; 0.37 mmol) in Et2O (2 ml) at −15° C. The mixture was allowed to warm up to room temperature and the stirring was continued for 4 h. This was poured onto ice (5 g) and the product was extracted with fresh Et2O (2×10 ml). The combined extracts were washed with 5% NaHCO3, H2O, brine, dried over anhydrous MgSO4 and filtered. The filtrate was evaporated under reduced pressure and the residue was purified by FCC (SiO2, hexane) to give the title compound (0.04 g; 40%) as a colourless solid. 1H-NMR (CDCl3) 7.28 (d, 2H, J=8 Hz); 7.13 (d, 2H, J=8 Hz); 4.48 (s, 2H); 2.57 (t, 2H, J=7.9 Hz); 1.57 (m, 2H); 1.26 (m, 10H); 0.86 (t, 3H, J=7 Hz).
Reaction SMILES: C(N(CC)CC)C.C(Cl)Cl.[CH:11]1([CH2:14][N:15]2[C:23]([N:24]3[CH2:29][CH2:28][NH:27][C@@H:26]([CH3:30])[CH2:25]3)=[N:22][C:21]3[C:16]2=[N:17][C:18]([C:37]2[CH:38]=[N:39][C:40]([NH2:43])=[N:41][CH:42]=2)=[N:19][C:20]=3[N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH2:13][CH2:12]1.[C:44](OC(=O)C)(=[O:46])[CH3:45]>C(Cl)Cl.CO>[C:44]([N:27]1[CH2:28][CH2:29][N:24]([C:23]2[N:15]([CH2:14][CH:11]3[CH2:13][CH2:12]3)[C:16]3[C:21]([N:22]=2)=[C:20]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[N:19]=[C:18]([C:37]2[CH:42]=[N:41][C:40]([NH2:43])=[N:39][CH:38]=2)[N:17]=3)[CH2:25][C@@H:26]1[CH3:30])(=[O:46])[CH3:45]
Reactant: C[C@H]1CN(c2nc3c(N4CCOCC4)nc(-c4cnc(N)nc4)nc3n2CC2CC2)CCN1
Reactant: CC(=O)OC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CO
Product: CC(=O)N1CCN(c2nc3c(N4CCOCC4)nc(-c4cnc(N)nc4)nc3n2CC2CC2)C[C@@H]1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 98 %

Procedure:
Triethylamine (80.3 μl, 0.58 mmol) was added to a methylene chloride solution (3.0 ml) of 5-{9-(cyclopropylmethyl)-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (108.1 mg, 0.24 mmol) at room temperature followed by the addition of acetic anhydride (27.2 μl, 0.29 mmol) with ice cooling. The resulting mixture was stirred at room temperature for 2 hours and then the reaction mixture was poured into methylene chloride-methanol (10:1), washed with water, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was purified by medium pressure silica gel column chromatography (methylene chloride:methanol=49:1 to 19:1) to give the title compound (115.8 mg, 98%) as a pale yellow solid.