Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][C@@:27]12[C:45](=[O:46])[O:44][C@@H:29]([C@H:30]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=3)[CH:31]=[CH:32]1)[CH2:28]2)(C(C)(C)C)(C)C.Cl>C1COCC1>[OH:26][C@@:27]12[C:45](=[O:46])[O:44][C@@H:29]([C@H:30]([O:33][CH2:34][C:35]3[CH:36]=[CH:37][C:38]([N+:41]([O-:43])=[O:42])=[CH:39][CH:40]=3)[CH:31]=[CH:32]1)[CH2:28]2
Reactant: CC(C)(C)[Si](C)(C)O[C@@]12C=C[C@@H](OCc3ccc([N+](=O)[O-])cc3)[C@@H](C1)OC2=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: [F-]
Solvent: C1CCOC1
Product: O=C1O[C@@H]2C[C@@]1(O)C=C[C@H]2OCc1ccc([N+](=O)[O-])cc1
Reaction time: 0.5 h
Yield: 43.3 %

Procedure:
Tetrabutylammonium fluoride (0.25 mL, 0.25 mmol, 1.0 M commercial solution in THF) was added to a solution of silyl ether VII (95 mg, 0.23 mmol) in 2 mL of dry THF under an argon atmosphere and at 0° C. After stirring for 30 minutes at said temperature, it was acidulated with 10% HCl and the organic phase was extracted with dichloromethane (3×15 mL). The pooled organic phase was dried (Na2SO4 anh.), filtered and concentrated under reduced pressure. The obtained residue was purified by means of flash chromatography in silica gel (diethyl ether) to give 29 mg of alcohol VIII in a pale yellow oil form (43%). [α]25D−265.5° (c 1.2 in CHCl3); 1H-NMR (250 MHz, CDCl3, δ) 8.22 (d, 2H, J 8.7), 7.51 (d, 2H, J 8.7), 6.17 (d, 1H, J 9.8), 5.82 (ddd, 1H, J 9.8, 3.3 and 1.0), 4.81 (m, 1H), 4.78 (s, 2H), 4.02 (t, 1H, J 3.3), 3.35 (broad s, 1H) and 2.44 (m, 2H); 13C-NMR (63 MHz, CDCl3, δ) 177.2, 147.6, 144.8, 137.4, 127.7, 125.1, 123.8, 74.5, 73.4, 72.2, 71.0 and 36.9; IR (NaCl)/cm−1 3405 and 1784; EM-IQ+ (m/z) 292 (MH+); HRMS calculated for C14H14O6N (MH+): 292.0821, 292.0826 found.
Reaction SMILES: [NH2:1][C:2]1[CH:35]=[CH:34][C:5]([C:6]([N:8]([CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([C:25](=[O:33])[C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH2:21][CH2:20]2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[O:7])=[CH:4][CH:3]=1.[C:36](Cl)(=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38]>>[C:36]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]([CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([C:25](=[O:33])[C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)[CH2:21][CH2:20]2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[O:7])=[CH:34][CH:35]=1)(=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38]
Reactant: CC(C)(C)C(=O)Cl
Reactant: COc1ccccc1N(CCN1CCC(C(=O)c2ccc(F)cc2)CC1)C(=O)c1ccc(N)cc1
Product: COc1ccccc1N(CCN1CCC(C(=O)c2ccc(F)cc2)CC1)C(=O)c1ccc(NC(=O)C(C)(C)C)cc1
Yield: 91.3 %

Procedure:
Using 4-amino-N-{2-[4-(4-fluorobenzoyl)piperidino]ethyl}-N-(2-methoxyphenyl)benzamide (200.0 mg, 0.42 mmol) and pivaloyl chloride (0.062 ml, 0.51 mmol), the procedure of Inventive Example 94 was repeated to obtain 214.6 mg (91.2%) of the title compound in a colorless amorphous form.
Reaction SMILES: [Br:1]Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:22]([C:24]1[CH:29]=[CH:28][N:27]=[C:26]([CH2:30]O)[CH:25]=1)#[N:23]>C(Cl)Cl>[C:22]([C:24]1[CH:29]=[CH:28][N:27]=[C:26]([CH2:30][Br:1])[CH:25]=1)#[N:23]
Reactant: BrBr
Reactant: N#Cc1ccnc(CO)c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: N#Cc1ccnc(CBr)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 102.8 %

Procedure:
Bromine (1.07 mL, 20.8 mmol) was added slowly at 0° C. to a solution of triphenylphosphine (5.53 g, 21.1 mmol) in methylene chloride (97 mL). The solution was warmed to room temperature and a white precipitate was observed. 4-Cyano-2-hydroxymethylpyridine 36 (2.61 g, 19.5 mmol) in methylene chloride (20 mL) was added dropwise and the reaction mixture was stirred at room temperature overnight. The reaction mixture was partitioned between water and methylene chloride. The organic layer was washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to give a white solid. Purification by flash column chromatography (silica, 99:1 methylene chloride/methanol) gave 4-cyano-2-bromomethylpyridine (3.95 g), which was used immediately in the next step without further purification: 1H NMR (300 MHz, CDCl3) δ 8.76 (d, J=5.0 Hz, 1H), 7.7 (s, 1H), 7.46 (dd, J=5.0, 1.3 Hz, 1H), 4.58 (s, 2H).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([O:19]/[C:20](/[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:21]\[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2F)[O:7][C@H:6]1[CH2:34][O:35][C:36](=[O:38])[CH3:37])(=[O:3])[CH3:2].[Br:39]C1C=C(CC(=O)C(OCC)=O)C=CC=1.[H-].[Na+].[Br-].C(O[C@@H]1[C@@H](OC(=O)C)[C@H](OC(=O)C)[C@@H](COC(=O)C)O[C@@H]1O)(=O)C>>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([O:19]/[C:20](/[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:21]\[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Br:39])[CH:23]=2)[O:7][C@H:6]1[CH2:34][O:35][C:36](=[O:38])[CH3:37])(=[O:3])[CH3:2]
Reactant: CCOC(=O)/C(=C/c1ccccc1F)O[C@H]1O[C@@H](COC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CCOC(=O)C(=O)Cc1cccc(Br)c1
Agent: CC(=O)OC[C@H]1O[C@H](O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: [Br-]
Agent: [H-]
Product: CCOC(=O)/C(=C/c1cccc(Br)c1)O[C@H]1O[C@@H](COC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Yield: 24 %

Procedure:
The title compound was prepared as described for C4 using Ethyl 3-(3-bromophenyl)-2-oxopropanoate B16 (100 mg, 0.369 mmol), sodium hydride (9.74 mg, 0.406 mmol) and 2,3,4,6 tetra-O-acetyl-α-D-glucose bromide (152 mg, 0.369 mmol). The resulting compound was isolated in the form of white solid in 24% yield.
Reaction SMILES: C(O[CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH2:17])[C:15](=[O:18])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=O)C.[NH2:19][C:20]1[CH:25]=[C:24]([NH2:26])[N:23]([CH2:27][CH3:28])[C:22](=[S:29])[N:21]=1.CO.N>O1CCOCC1>[NH2:17][CH:16]1[C:15](=[O:18])[N:10]2[C:11]([C:12]([O-:14])=[O:13])=[C:6]([CH2:5][S:29][C:22]3[N:21]=[C:20]([NH2:19])[CH:25]=[C:24]([NH2:26])[N+:23]=3[CH2:27][CH3:28])[CH2:7][S:8][C@H:9]12
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Reactant: CCn1c(N)cc(N)nc1=S
Agent: N
Solvent: CO
Solvent: C1COCCO1
Product: CC[n+]1c(N)cc(N)nc1SCC1=C(C(=O)[O-])N2C(=O)C(N)[C@H]2SC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 75.1 %

Procedure:
Under an anhydrous condition, a solution containing 2.72 g of 3-acetoxymethyl-7-amino-3cephem-4-carboxylic acid and 1.8 g of 4,6-diamino-1-ethyl-2-(1H)-pyrimidinethione suspended in 20 ml of dry dioxane was cooled to 0° C.; and 3 ml of boron trifluoride diethylether was added. The temperature of the reaction solution was increased to 40° C.; the solution was stirred for one hour; and then 10 ml of methyl alcohol was added. The resultant solution was stirred for 10 minutes and was added with 30 ml of ice water. The pH of the solution was adjusted to 7.1 by adding aqueous ammonia solution After concentration under a reduced pressure, e.g., about 20 mmHg, the solution was adjusted to pH 3.6 with 2N-aqueous hydrochloric acid; and allowed to stand at a room temperature for 24 hrs. The precipitates resulted from the reaction solution were filtered, washed with 10 ml of distilled water and with 10 ml of methyl alcohol, and dried to give 2.87 g of the title compound as a solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([O:10]CC)=[O:9])=[CH:6][N:5]=[C:4]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[N:14]=2)[N:3]=1.[OH-].[Na+].Cl>O1CCOCC1>[NH2:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[C:4]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[N:14]=2)[N:3]=1
Reactant: CCOC(=O)c1cnc(-c2nn(Cc3ccccc3F)c3ncccc23)nc1N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: Nc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)ncc1C(=O)O
Temperature: 60 °C
Reaction time: 4 h

Procedure:
1000 mg (2.55 mmol) of ethyl 4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidine-5-carboxylate (example 101A) were suspended in 80 ml of dioxane and admixed cautiously with 50.1 ml (948 mmol) of aqueous sodium hydroxide solution (50% by weight). The mixture was then stirred at 60° C. for 4 h and then poured onto 200 ml of ice-water. Concentrated hydrochloric acid was used to cautiously adjust the mixture to pH 2, and the precipitate observed was removed by means of filtration. The precipitate was washed with a little water and finally dried under high vacuum. Thus, 993 mg (approx. 105% of theory, the batch probably still contained small amounts of inorganic salts) of the target compound were obtained.
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[C:11](=[O:13])[N:10]([C:14]1[CH:22]=[C:21]3[C:17]([CH:18]=[CH:19][N:20]3[CH2:23][C:24]([O:26]CC)=[O:25])=[CH:16][CH:15]=1)[CH2:9]2>O.C1COCC1.CO>[CH3:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[C:11](=[O:13])[N:10]([C:14]1[CH:22]=[C:21]3[C:17]([CH:18]=[CH:19][N:20]3[CH2:23][C:24]([OH:26])=[O:25])=[CH:16][CH:15]=1)[CH2:9]2
Reactant: CCOC(=O)Cn1ccc2ccc(N3Cc4cccc(C)c4C3=O)cc21
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Cc1cccc2c1C(=O)N(c1ccc3ccn(CC(=O)O)c3c1)C2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
NaOH (1.86 mmol, 1.3 equiv.), dissolved in water (6 ml), was added to a solution of ethyl 2-(6-(7-methyl-1-oxoisoindolin-2-yl)-1H-indol-1-yl)acetate (1.44 mmol, 1 equiv.) in THF/MeOH (1:1, 5 ml), and the mixture was stirred for 2 h at 25° C. The reaction solution was concentrated under reduced pressure, and the aqueous residue was adjusted to pH 3 with 1 M HCl and extracted with ethyl acetate (3×50 ml). The combined organic phases were dried over Na2SO4 and concentrated under reduced pressure. Yield: quantitative
Reaction SMILES: [Li]C.C[Si](C)(C)[O:5][C:6]([CH3:8])=[CH2:7].[CH2:11]([Si:14]1(Cl)[O:18][C@@H:17]([C:19]([O:22][CH3:23])([CH3:21])[CH3:20])[C@H:16]([C:24]([CH3:28])([O:26][CH3:27])[CH3:25])[O:15]1)[CH:12]=[CH2:13]>CCCCC>[CH2:11]([Si:14]1([O:5][C:6]([CH3:8])=[CH2:7])[O:18][C@@H:17]([C:19]([O:22][CH3:23])([CH3:21])[CH3:20])[C@H:16]([C:24]([CH3:28])([O:26][CH3:27])[CH3:25])[O:15]1)[CH:12]=[CH2:13]
Reactant: C=CC[Si]1(Cl)O[C@@H](C(C)(C)OC)[C@H](C(C)(C)OC)O1
Reactant: C=C(C)O[Si](C)(C)C
Agent: [Li]C
Solvent: CCCCC
Product: C=CC[Si]1(OC(=C)C)O[C@@H](C(C)(C)OC)[C@H](C(C)(C)OC)O1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 43.2 %

Procedure:
To a cooled (0° C.) solution of MeLi (13.0 mL; 21 mmol; 1.6 M in Et2O) was added 2-(trimethylsilyloxy)propene (2.8 g; 21 mmol). The solution was stirred 30 minutes at 0° C., and then warmed to room temperature and was stirred for 1 hour. The mixture was recooled to 0° C., and (4R,5R)-2-allyl-2-chloro-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3,2]dioxasilolane (6.6 g; 21 mmol) was added. The mixture was warmed to room temperature and stirred for 2 hours. The solution was diluted with pentane (20 mL), and the mixture was then filtered through a pad of celite. The filtrate was concentrated, and the residue was distilled under reduced pressure to give 3.0 g (43%) of (4R,5R)-2-allyl-2-isopropenyloxy-4,5-bis-(1-methoxy-1-methyl-ethyl)-[1,3,2]dioxasilolane as a clear, colorless liquid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:25]([O-:27])=[O:26])=[C:6]([CH:24]=1)[O:7][C@@H:8]1[CH2:12][O:11][C@@H:10]2[C@H:13](OS(C(F)(F)F)(=O)=O)[CH2:14][O:15][C@H:9]12.[C-:28]#[N:29].[K+].C1OCCOCCOCCOCCOCCOC1>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:25]([O-:27])=[O:26])=[C:6]([CH:24]=1)[O:7][C@H:8]1[C@H:9]2[O:15][CH2:14][C@H:13]([C:28]#[N:29])[C@H:10]2[O:11][CH2:12]1
Reactant: [C-]#N
Reactant: O=[N+]([O-])c1ccc(F)cc1O[C@@H]1CO[C@H]2[C@@H]1OC[C@H]2OS(=O)(=O)C(F)(F)F
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: C1CCOC1
Product: N#C[C@H]1CO[C@H]2[C@@H]1OC[C@H]2Oc1cc(F)ccc1[N+](=O)[O-]

Procedure:
0.4 g (1.0 mmol) [(3R,3aR,6R,6aS)-3-(5-fluoro-2-nitro-phenoxy)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]trifluoromethanesulfonate (prepared as described for III.3 from III.1), 0.1 g (1.5 mmol) potassium cyanide and 0.3 g (1.0 mmol) 18-crown-6 in THF is stirred at RT for 3 h. The reaction mixture is filtered through celite and evaporated. The residue is taken up in EtOAc washed with water, dried and evaporated. The residue is purified by FC.
Reaction SMILES: [N:1]([CH2:4][CH2:5][NH:6]C(=O)CCCCCCCCCCCCC)=[N+:2]=[N-:3].[CH3:22][N:23]([CH3:38])[C:24]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:25]=1[CH:26]=[CH:27][CH:28]=[C:29]2[S:34](Cl)(=[O:36])=[O:35].N(CCN)=[N+]=[N-].C(N(CC)CC)C>ClCCl>[N:1]([CH2:4][CH2:5][NH:6][S:34]([C:29]1[C:30]2[C:25](=[C:24]([N:23]([CH3:38])[CH3:22])[CH:33]=[CH:32][CH:31]=2)[CH:26]=[CH:27][CH:28]=1)(=[O:36])=[O:35])=[N+:2]=[N-:3]
Reactant: CN(C)c1cccc2c(S(=O)(=O)Cl)cccc12
Reactant: CCCCCCCCCCCCCC(=O)NCCN=[N+]=[N-]
Agent: [N-]=[N+]=NCCN
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)c1cccc2c(S(=O)(=O)NCCN=[N+]=[N-])cccc12
Yield: 86 %

Procedure:
As in the synthesis of N-(2-azidoethyl)tetradecanamide, 5-(dimethylamino)naphthalene-1-sulfonyl chloride (0.321 g, 1.19 mmol) was reacted with 2-azidoethanamine (0.103 g, 1.19 mmol) and triethylamine (0.241 g, 2.38 mmol) in dichloromethane (5 mL) to give N-(2-azidoethyl)-5-(dimethylamino)naphthalene-1-sulfonamide (0.328 g, 86% yield). 1H NMR (300 MHz, CDCl3) δ 8.52 (d, J=8.4 Hz, 1H), δ 8.28 (d, J=8.4 Hz, 1H), δ 8.22 (d, J=0.9 Hz, 1H), δ 7.53 (t, J=8.1 Hz, 1H), δ 7.50 (t, J=7.5 Hz, 1H), δ 7.17 (d, J=7.8 Hz, 1H), δ 5.58 (t, J=1.8 Hz, 1H), δ 3.28 (t, J=5.7 Hz, 2H), δ 3.03 (q, J=6.3, 5.7 Hz, 2H), δ 2.85 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3) δ 152.3, 134.8, 130.9, 130.1, 129.7, 128.9, 123.4, 118.9, 115.6, 51.0, 45.6, 42.6 ppm; HRMS (ESI) calcd for C14H17N5O2S (M+) 319.1103. found 319.1104.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([C@@H:10]([NH2:15])[CH2:11][CH2:12][CH2:13][CH3:14])[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2].C([O:20][C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]1[CH:34]=[CH:33][C:32]([CH2:35][N:36]2[C:44]3[C:39](=[CH:40][C:41]([C:45](O)=[O:46])=[CH:42][CH:43]=3)[C:38]([CH3:48])=[C:37]2[CH3:49])=[CH:31][CH:30]=1)=[O:22])(C)(C)C>>[CH:1]([C:4]1[CH:5]=[C:6]([C@@H:10]([NH:15][C:45]([C:41]2[CH:40]=[C:39]3[C:44](=[CH:43][CH:42]=2)[N:36]([CH2:35][C:32]2[CH:31]=[CH:30][C:29]([C:24]4[C:23]([C:21]([OH:22])=[O:20])=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:34][CH:33]=2)[C:37]([CH3:49])=[C:38]3[CH3:48])=[O:46])[CH2:11][CH2:12][CH2:13][CH3:14])[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CCCC[C@H](N)c1cccc(C(C)C)c1
Reactant: Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)OC(C)(C)C)cc2)c2ccc(C(=O)O)cc12
Product: CCCC[C@H](NC(=O)c1ccc2c(c1)c(C)c(C)n2Cc1ccc(-c2ccccc2C(=O)O)cc1)c1cccc(C(C)C)c1

Procedure:
The title compound was prepared following the same general protocol as described in Step 8-9, Example 1, using the (S)-1-(3-isopropylphenyl)pentan-1-amine and the 1-((2′-(tert-butoxycarbonyl)-[1,1′-biphenyl]-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylic acid. ESI-MS (m/z): 587 [M+H]+.
Reaction SMILES: Br[C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH3:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>>[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:2]2[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=2)[CH2:13][CH2:12]1
Reactant: CN1CCNCC1
Reactant: O=c1[nH]cc(Br)c(=O)[nH]1
Product: CN1CCN(c2c[nH]c(=O)[nH]c2=O)CC1
Yield: 91 %

Procedure:
The title compound was obtained according to the procedure described for the synthesis of Example 10 (Step1), starting from 5-bromouracil (0.10 g, 0.52 mmol) and 20 equivalents of 1-methyl piperazine. The crude was purified by washing with water (10 dichloromethane (5 mL) and then collected by dispersion in EtOAc. (10 mL). The solvent was removed by evaporation to afford the title compound (0.15 g, 91%) as white powder. 1H NMR (400 MHz, DMSO-d6): δ 2.18 (s, 3H), 2.34-2.42 (m, 4H), 2.74-2.84 (m, 4H), 6.72 (s, 1H). 10.41 (br s, 1H), 11.04 (br s, 1H).
Reaction SMILES: [Si]([O:8][C@@H:9]1[C@@:42]2([CH3:43])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:41]2[CH2:40][CH2:39][C@@:38]2([CH3:44])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([O:23][CH2:24]/[CH:25]=[CH:26]/[C:27]([CH3:37])([O:29][Si](CC)(CC)CC)[CH3:28])[CH3:22])[CH2:12][C@@H:11]([O:45][Si](C(C)(C)C)(C)C)[CH2:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[OH:8][C@@H:9]1[C@@:42]2([CH3:43])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:41]2[CH2:40][CH2:39][C@@:38]2([CH3:44])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([O:23][CH2:24]/[CH:25]=[CH:26]/[C:27]([OH:29])([CH3:28])[CH3:37])[CH3:22])[CH2:12][C@@H:11]([OH:45])[CH2:10]1
Reactant: CC[Si](CC)(CC)OC(C)(C)/C=C/CO[C@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C[C@@H](OC/C=C/C(C)(C)O)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Yield: 86.2 %

Procedure:
By the same procedure as in Example 9, 1α,3β-bis(tert-butyldimethylsilyloxy)-20(R)-{(E)-(4-methyl-4-triethylsilyloxy-2-pentenyloxy)}pregna-5,7,16-triene (71.0 mg, 0.0920 mmol), tetrahydrofuran (3 ml) and 1M tetra-n-butylammonium fluoride solution in tetrahydrofuran (2 ml) were reacted (heating under reflux for 5.5 hours) and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×1, dichloromethane:ethyl acetate:ethanol=20:80:1, developed once) to give the title compound as a colorless oil (34.0 mg, 86%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:3]=1.C([Sn](CCCC)(CCCC)/[CH:31]=[CH:32]\[O:33][CH2:34][CH3:35])CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:34]([O:33]/[CH:32]=[CH:31]\[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:3]=1)[CH3:35]
Reactant: CCCC[Sn](/C=C\OCC)(CCCC)CCCC
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2cc(Cl)nc(C(F)(F)F)n2)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CCO/C=C\c1cc(NC2CCN(C(=O)OC(C)(C)C)CC2)nc(C(F)(F)F)n1
Temperature: 110 °C
Reaction time: 8 h
Yield: 73.9 %

Procedure:
A mixture of tert-butyl 4-{[6-chloro-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate (1.0 g, 2.6 mmol, from Step 1), tributyl[(Z)-2-ethoxyvinyl]stannane (0.96 mL, 2.9 mmol, Synthonix Corp.) and tetrakis(triphenylphosphine)palladium(0) (0.15 g, 0.13 mmol, Strem) in toluene (3.0 mL) was degassed and then heated to 110° C. for 3 hours, then lowered to 90° C. overnight. The mixture was concentrated and flash chromatographed on a 120 g silica gel cartridge, eluting with a gradient from 0-20% EtOAc in hexanes to afford product as a white solid (0.8 g, 73%). 1H NMR (400 MHz, CDCl3) δ 7.08 (s, 1H), 6.58 (d, J=7.1 Hz, 1H), 5.40 (d, J=7.1 Hz, 1H), 4.98 (br s, 1H), 4.18-4.00 (m, 4H), 3.82 (br s, 1H), 2.94 (t, J=11.7 Hz, 2H), 2.12-1.95 (m, 2H), 1.52-1.31 (m, 14H). 19F NMR (376 MHz, CDCl3) δ −71.77 (s). LCMS (M+H): 417.2.
Reaction SMILES: [CH3:1][C:2]1[N:3]([S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C:4]([C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)=[CH:5][C:6]=1[CH2:7][OH:8].C[N+]1([O-])CCOCC1>[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[CH3:1][C:2]1[N:3]([S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:15])=[O:16])[C:4]([C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)=[CH:5][C:6]=1[CH:7]=[O:8]
Reactant: Cc1c(CO)cc(-c2ccsc2)n1S(=O)(=O)c1ccccc1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Product: Cc1c(C=O)cc(-c2ccsc2)n1S(=O)(=O)c1ccccc1
Yield: 101263.7 %

Procedure:
Using [2-methyl-1-(phenylsulfonyl)-5-(3-thienyl)-1H-pyrrol-3-yl]methanol (307 mg), tetra-n-propylammonium perruthenate (26.4 mg), N-methylmorpholine N-oxide (216 mg) and molecular sieves 4A powder (215 mg), a procedure as in Reference Example 6 was performed to give the title compound as a brown oil (yield 309 g, 76%).
Reaction SMILES: [CH2:1]([NH2:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:10][O:11][C:12](=[O:30])[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:20]=[C:21](Cl)[C:22]3[CH:27]=[C:26]([CH3:28])[S:25][C:23]=3[N:24]=2)=[CH:15][CH:14]=1>>[CH3:10][O:11][C:12](=[O:30])[C:13]1[CH:14]=[CH:15][C:16]([C:19]2[N:20]=[C:21]([NH:9][CH2:1][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[C:22]3[CH:27]=[C:26]([CH3:28])[S:25][C:23]=3[N:24]=2)=[CH:17][CH:18]=1
Reactant: NCCc1ccccc1
Reactant: COC(=O)c1ccc(-c2nc(Cl)c3cc(C)sc3n2)cc1
Product: COC(=O)c1ccc(-c2nc(NCCc3ccccc3)c3cc(C)sc3n2)cc1

Procedure:
The reaction procedure as above wherein phenethylamine is reacted with 4-(4-chloro-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl)-benzoic acid methylester yields 4-(4-phenethylamino-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl)-benzoic acid methylester;
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:13]=[C:12]([OH:14])[C:11]([O:15][CH3:16])=[CH:10][C:4]=2[S:5][C:6]=1[C:7]([OH:9])=[O:8].[N+:17]([O-])([OH:19])=[O:18]>C(OCC)(=O)C.ClCCl>[Cl:1][C:2]1[C:3]2[C:13]([N+:17]([O-:19])=[O:18])=[C:12]([OH:14])[C:11]([O:15][CH3:16])=[CH:10][C:4]=2[S:5][C:6]=1[C:7]([OH:9])=[O:8]
Reactant: COc1cc2sc(C(=O)O)c(Cl)c2cc1O
Reactant: O=[N+]([O-])O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COc1cc2sc(C(=O)O)c(Cl)c2c([N+](=O)[O-])c1O
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
3-Chloro-5-hydroxy-6-methoxy-benzo[b]thiophene-2-carboxylic acid (0.28 g) was dissolved in ethyl acetate and a solution of nitric acid in dichloromethane (2M, 0.75 ml) was gradually added at 20° C. into. The solution was stirred at room temperature for 10 min and then it was poured into ice-cold water and extracted with ethyl acetate and evaporated to dryness.
Reaction SMILES: Cl[CH2:2]C1C=C(C=CC=1OC)C=O.CC1C=CC=C(C)C=1O.C([O-])([O-])=O.[K+].[K+].[NH2:28][C:29]1[CH:43]=[CH:42][CH:41]=[CH:40][C:30]=1[C:31]([NH:33][CH2:34][C:35]1[O:36][CH:37]=[CH:38][CH:39]=1)=[O:32].FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>C(#N)C.CCO>[O:36]1[CH:37]=[CH:38][CH:39]=[C:35]1[CH2:34][N:33]1[C:31](=[O:32])[C:30]2[C:29](=[CH:43][CH:42]=[CH:41][CH:40]=2)[NH:28][CH2:2]1
Reactant: Nc1ccccc1C(=O)NCc1ccco1
Reactant: COc1ccc(C=O)cc1CCl
Agent: Cc1cccc(C)c1O
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCO
Solvent: CC#N
Product: O=C1c2ccccc2NCN1Cc1ccco1
Temperature: 150 °C
Yield: 55409.6 %

Procedure:
To a solution of 3-(chloromethyl)-4-methoxybenzaldehyde (85 mg, 0.46 mmol, 1.0 equiv) and 2,6-dimethylphenol (62 mg, 0.51 mmol, 1.1 equiv) in 3.0 mL of anhydrous acetonitrile, we added K2CO3 (320 mg, 2.3 mmol, 5.0 eq). The mixture was heated in a microwave reactor for 30 min at 150° C. After filtering off the solid and removing the solvent, 2-amino-N-(furan-2-ylmethyl)benzamide (110 mg, 0.51 umol, 1.1 equiv) in 5 mL of EtOH was added followed by addition of Ytterbium trifluoromethanesulfonate (57 mg, 0.02 umol, 0.2 equiv). The mixture was heated at 80° C. for 2 hours. The product was isolated via preparative HPLC purification and solvent was removed via reduced pressure lyophilization to give 2434(2,6-dimethylphenoxy)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one (64.5 mg, 30%) as a white solid after triturating with diethyl ether. 1HNMR (400 MHz, DMSO-d6) δ ppm 2.16 (s, 6H), 3.77 (s, 3 H), 3.86 (d, J=15.6 Hz, 1 H), 4.69 (d, J=1.9 Hz, 2 H), 5.19 (d, J=15.4 Hz, 1 H), 5.75 (d, J=2.3, Hz, 1 H), 6.30 (d, J=3.2 Hz, 1 H), 6.39 (dd, J=3.2, 1.9 Hz, 1 H), 6.62-6.70 (m, 2 H), 6.86-6.97 (m, 1 H), 6.99-7.04 (m, 3 H), 7.19-7.29 (m, 2 H), 7.32 (d, J=2.3 Hz, 1 H), 7.49 (d, J=2.4, Hz, 1 H), 7.57 (dd, J=1.8, 0.7 Hz, 1 H), 7.68 (dd, J=7.9, 1.5 Hz, 1 H); HPLC: tR=6.88 min, UV254=97%; HRMS (ESI): m/z calculated for C29H28N2O4 [M+1]+469.2132, found 469.2138.