Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:7]2[N:8]=[CH:9][N:10]([C@@H:11]3[CH2:15][C@@H:14](O)[CH:13]=[CH:12]3)[C:6]=2[C:5]([F:17])=[CH:4][N:3]=1.CCN(S(F)(F)[F:24])CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:17][C:5]1[C:6]2[N:10]([C@@H:11]3[CH2:15][C@H:14]([F:24])[CH:13]=[CH:12]3)[CH:9]=[N:8][C:7]=2[C:2]([NH2:1])=[N:3][CH:4]=1
Reactant: Nc1ncc(F)c2c1ncn2[C@H]1C=C[C@H](O)C1
Reactant: CCN(CC)S(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Nc1ncc(F)c2c1ncn2[C@H]1C=C[C@@H](F)C1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
(1R,4R)-4-(4-amino-7-fluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol (4-3) (600 mg, 2.6 mmol, 1 eq) was dissolved in DCM (120 mL). The mixture was cooled to 0° C. and DAST (1.6 mL, 12.0 mmol, 4.7 eq) was added. The resulting mixture was stirred at the same temperature for 1 hour. Upon disappearance of starting material, the reaction mixture was poured over NaHCO3 (30 mL) and extracted with CHCl3 (3×50 mL). The combined organics were dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (0-100% Acetone in DCM) to afford 7-fluoro-1-((1R,4S)-4-fluorocyclopent-2-enyl)-1H-imidazo[4,5-c]pyridin-4-amine (4-5) as a white solid. LRMS m/z (M+H) 236.9.0 found, 237.1 required.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:12]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[CH:11][NH:10][N:9]=2)[C:5]([OH:19])=[CH:4][C:3]=1[OH:20].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:28][CH2:29][OH:30]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH2:28][CH2:29][OH:30])[CH2:15][CH2:14]3)=[CH:11][NH:10][N:9]=2)[C:5]([OH:19])=[CH:4][C:3]=1[OH:20]
Reactant: Oc1cc(O)c(-c2n[nH]cc2N2CCNCC2)cc1Cl
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: OCCN1CCN(c2c[nH]nc2-c2cc(Cl)c(O)cc2O)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 20.2 %

Procedure:
A mixture of 4-chloro-6-(4-piperazin-1-yl-1H-pyrazol-3-yl)-benzene-1,3-diol (43 mg, 0.146 mmol), cesium carbonate (48 mg, 0.146 mmol), 2-bromoethanol (0.025 ml, 0.35 mmol) and dimethylformamide (1 ml) was stirred at room temperature for 3 days. The mixture was evaporated to dryness and applied to a bond elute cartridge (5 g) with dichloromethane:methanol (49:1), then eluting with dichloromethane followed by dichloromethane:ethanol:ammonia (50:8:1 then 20:8:1) gave 4-chloro-6-{4-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-1H-pyrazol-3-yl}-benzene-1,3-diol as a white solid (10 mg)
Reaction SMILES: [ClH:1].C(OC([N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=1)=O)(C)(C)C>O1CCOCC1>[ClH:1].[CH3:33][O:32][C:28]1[CH:27]=[C:26]([CH2:25][CH2:24][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[O:17][CH2:16][CH2:15][CH:10]2[CH2:11][CH2:12][CH2:13][CH2:14][NH:9]2)[CH:31]=[CH:30][CH:29]=1
Reactant: COc1cccc(CCc2ccccc2OCCC2CCCCN2C(=O)OC(C)(C)C)c1
Agent: Cl
Solvent: C1COCCO1
Product: COc1cccc(CCc2ccccc2OCCC2CCCCN2)c1
Reaction time: 2.5 h
Yield: 40 %

Procedure:
1 ml of a 4N solution of hydrogen chloride in dioxane was added to a solution of 0.63 g of 1-t-butoxycarbonyl-2-(2-{2-[2-(3-methoxyphenyl)ethyl]phenoxy}ethyl)piperidine [prepared as described in step (a) above] in 1 ml of dioxane, and the resulting solution was allowed to stand at room temperature for 2.5 hours. At the end of this time, it was concentrated by distillation under reduced pressure. The resulting residue was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and concentrated by distillation under reduced pressure. The resulting residue was dissolved in ethanol, and the solution was adsorbed on a Column packed with CM Sephadex C-25 (H+ type) (Sephadex is a trade mark). The column was washed with ethanol and eluted with a 0.1N solution of hydrogen chloride in ethanol. The eluate was concentrated by evaporation under reduced pressure and dried in vacuo, to give 0.22 g (yield 40%) of the title compound as a colorless oil.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][C:8](=[O:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH:12]1([Mg]Cl)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>C1COCC1>[CH:12]1([C:8]2([OH:11])[CH2:7][CH2:6][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:10][CH2:9]2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: Cl[Mg]C1CCCCC1
Reactant: O=C1CCC2(CC1)OCCO2
Solvent: C1CCOC1
Product: OC1(C2CCCCC2)CCC2(CC1)OCCO2
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
To a solution of 1,4-dioxaspiro[4.5]decan-8-one (5.00 g, 24.0 mmol) in THF (100 mL) was dropwise added cyclohexylmagnesium chloride (2.0 M in diethyl ether, 24.0 mL, 48.0 mmol) at −78° C. over 10 min. The mixture was stirred at 0° C. for 1.5 h, and then quenched with aqueous NH4Cl (100 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (50 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel, hexane to 70:30 hexane/EtOAc) to give crude 8-cyclohexyl-1,4-dioxaspiro[4.5]decan-8-ol as a colorless solid. To a solution of crude 8-cyclohexyl-1,4-dioxaspiro[4.5]decan-8-ol (<24.0 mmol) in THF (45 mL) was added 3 M HCl (15 mL). The mixture was stirred at room temperature for 4 h, and then poured into EtOAc (50 mL) and aqueous NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (20 mL×2). The combined organic layers were washed with brine (15 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel hexane to 70:30 hexane/EtOAc) to give the title compound (2.34 g, 37%) as a colorless solid:
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]([C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17](I)=[C:16]([N+:21]([O-:23])=[O:22])[CH:15]=2)=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[C:25]1([C:31]#[CH:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+].CCN(CC)CC>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Br:1][C:2]1[S:3][C:4]([C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:32]#[C:31][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:16]([N+:21]([O-:23])=[O:22])[CH:15]=2)=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)Cc1cc(C(=O)c2ccc(I)c([N+](=O)[O-])c2)sc1Br
Reactant: C#Cc1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CCOC(=O)Cc1cc(C(=O)c2ccc(C#Cc3ccccc3)c([N+](=O)[O-])c2)sc1Br
Yield: 72 %

Procedure:
A solution of 2 (2.00 g, 3.82 mmol), phenylacetylene (0.47 mL, 4.28 mmol), Pd(PPh3)2Cl2 (137 mg, 0.19 mmol), K2CO3 (542 mg, 3.92 mmol), and Et3N (0.55 mL, 3.95 mmol) in DMF (5 mL) was stirred for 24 h at room temperature. Water (10 mL) was added to the mixture and then extracted with Et2O (3×30 mL). The combined organic layer was washed with brine (3×15 mL), dried over MgSO4, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/5:1) of the residue gave 3 as a yellow amorphous solid (1.37 g, 72%). 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.63-7.61 (m, 2H), 7.52 (s, 1H), 7.43-7.37 (m, 3H), 4.19 (q, J=7.2 Hz, 2H), 3.67 (s, 2H), and 1.28 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 183.93, 169.64, 149.51, 142.13, 136.97, 136.36, 135.90, 135.24, 132.92, 132.52, 130.11, 128.82, 125.57, 124.25, 122.73, 122.06, 101.10, 84.72, 61.75, 35.26, and 14.42.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[N:6]([CH3:32])[C:7]([CH2:20][NH:21][S:22]([C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:24])=[O:23])=[CH:8][C:9](=[O:19])[C:10]=1[O:11]CC1C=CC=CC=1)=[O:4].C1(S(C(N)C2N(C)C(C(O)=O)=C(O)C(=O)C=2)(=O)=O)C=CC=CC=1>>[CH3:1][NH:2][C:3]([C:5]1[N:6]([CH3:32])[C:7]([CH2:20][NH:21][S:22]([C:25]2[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=2)(=[O:23])=[O:24])=[CH:8][C:9](=[O:19])[C:10]=1[OH:11])=[O:4]
Reactant: CNC(=O)c1c(OCc2ccccc2)c(=O)cc(CNS(=O)(=O)c2ccc(C)cc2)n1C
Agent: Cn1c(C(N)S(=O)(=O)c2ccccc2)cc(=O)c(O)c1C(=O)O
Product: CNC(=O)c1c(O)c(=O)cc(CNS(=O)(=O)c2ccc(C)cc2)n1C
Yield: 59.8 %

Procedure:
3-Hydroxy-1-methyl-4-oxo-6-[(toluene-4-sulfonylamino)-methyl]-1,4-dihydro-pyridine-2-carboxylic acid methylamide (16-06) (120.0 mg, 59.77%, purified by Prep-HPLC) was synthesized as an off white solid from 3-benzyloxy-1-methyl-4-oxo-6-[(toluene-4-sulfonylamino)-methyl]-1,4-dihydro-pyridine-2-carboxylic acid methylamide (15-06) (250.0 mg, 0.549 mmol) following the procedure described for 6-(benzene sulfonyl amino-methyl)-3-hydroxy-1-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid (14-01).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[N:8]=[C:7]([CH:9]=O)[CH:6]=[CH:5][CH:4]=1.Cl.Cl.[NH2:15][C:16]1[CH:17]=[CH:18][C:19]([N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([C:29]([N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])[CH2:24]2)=[N:20][C:21]=1[NH2:22].S(S([O-])=O)([O-])=O.[Na+].[Na+].C(O)C>O>[N:31]1([C:29]([C@@H:25]2[CH2:26][CH2:27][CH2:28][N:23]([C:19]3[N:20]=[C:21]4[NH:22][C:9]([C:7]5[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:12])([F:11])[F:1])[N:8]=5)=[N:15][C:16]4=[CH:17][CH:18]=3)[CH2:24]2)=[O:30])[CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: O=Cc1cccc(C(F)(F)F)n1
Reactant: Nc1ccc(N2CCC[C@@H](C(=O)N3CCCC3)C2)nc1N
Agent: Cl
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=C([C@@H]1CCCN(c2ccc3nc(-c4cccc(C(F)(F)F)n4)[nH]c3n2)C1)N1CCCC1
Temperature: 110 °C
Reaction time: 16 h
Yield: 23.9 %

Procedure:
Into a tube was added 6-(trifluoromethyl)picolinaldehyde (150 mg, 0.47 mmol), (R)-(1-(6-amino-5-nitropyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (Intermediate 1, Step 3) (82.2 mg, 0.47 mmol), sodium dithionite (310.7 mg, 1.78 mmol), ethanol (10 mL) and water (1.5 mL). The vessel was sealed and the reaction mixture was stirred at 110° C. for 16 h. The solvent was evaporated under reduced pressure and water was added to the resulting residue. The mixture was extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified via preparative TLC to afford the title compound (50 mg, 29%) as a yellow solid. MS (ES+APCI) (M+H) 445.2; LCMS retention time 2.657 min (Method G).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5](=[S:8])[NH:6][CH:7]=1.[C:9]([O:17][C@@H:18]1[C@H:22]([O:23][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:21]([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:20][C@H:19]1Cl)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CC)CC)C>ClCCl>[C:9]([O:17][C@@H:18]1[C@H:22]([O:23][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:21]([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[O:20][C@H:19]1[S:8][C:5]1[N:6]=[CH:7][C:2]([Cl:1])=[CH:3][N:4]=1)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(OC[C@H]1O[C@@H](Cl)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Reactant: S=c1ncc(Cl)c[nH]1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(OC[C@H]1O[C@@H](Sc2ncc(Cl)cn2)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 28 %

Procedure:
A mixture of 5-chloropyrimidine-2-thione (4.3 mmol), 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl chloride (4.3 mmol) and triethylamine (4.3 mmol) in dichloromethane (25 ml) was stirred together at room temperature for 4 h, the mixture evaporated and the residue triturated with water; the residue was the title compound; yield 28% 1H NMR (CDCl3): δ4.75 (CH2), 6.0-6.5 (4 H), 7.2-8.2 (3 Ph), 8.50 (H-4, H-6).
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[CH2:20][C:19](=O)[NH:18][C:17](=O)[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1ccc(C2CC(=O)NC(=O)C2)cc1OC1CCCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(C2CCNCC2)cc1OC1CCCC1

Procedure:
Following the procedure of Nacci et al, Vide Supra, reaction of 4(3-cyclopentyloxy-4-methoxyphenyl)-2,6-piperidinedione (12 mmol, 3.65 g) and lithium aluminum hydride (120 mmol, 4.56 g) in dry THF (240 mL) afforded the title compound as a light yellow waxy solid (2.71 g, 82%) of sufficient purity for subsequent transformations.
Reaction SMILES: C(N=S(C1C=CC(CN2C(=O)C3C(=CC=CC=3)C2=O)=CC=1)(C)=[O:5])#N.[C:25]([N:27]=[S:28]([C:32]1[CH:49]=[CH:48][C:35]([CH2:36][N:37]2[C:45](=[O:46])[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:38]2=[O:47])=[CH:34][CH:33]=1)[CH:29]([CH3:31])[CH3:30])#[N:26]>>[C:25]([N:27]=[S:28]([C:32]1[CH:49]=[CH:48][C:35]([CH2:36][N:37]2[C:45](=[O:46])[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:38]2=[O:47])=[CH:34][CH:33]=1)([CH:29]([CH3:31])[CH3:30])=[O:5])#[N:26]
Reactant: CS(=O)(=NC#N)c1ccc(CN2C(=O)c3ccccc3C2=O)cc1
Reactant: CC(C)S(=NC#N)c1ccc(CN2C(=O)c3ccccc3C2=O)cc1
Product: CC(C)S(=O)(=NC#N)c1ccc(CN2C(=O)c3ccccc3C2=O)cc1

Procedure:
The title compound is prepared in analogy to preparation 6c, substituting 2-(4-(N-cyano-S-methylsulfinimidoyl)benzyl)isoindoline-1,3-dione with 2-(4-(N-cyano-S-isopropylsulfinimidoyl)benzyl)isoindoline-1,3-dione (preparation 14a). ESI mass spectrum: [M+H]+=368; r.t. HPLC: 3.42 min (LCMS-FA-8).
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.Br[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([OH:25])([C:21]([F:24])([F:23])[F:22])[C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C>[F:18][C:17]([F:19])([F:20])[C:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][N:6]2[CH2:5][CH2:4][NH:3][C@@H:2]([CH3:1])[CH2:7]2)=[CH:11][CH:12]=1)([OH:25])[C:21]([F:22])([F:24])[F:23]
Reactant: C[C@H]1CNCCN1
Reactant: OC(c1ccc(CBr)cc1)(C(F)(F)F)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: C[C@H]1CN(Cc2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2)CCN1
Yield: 45.6 %

Procedure:
(S)-2-Methylpiperazine (28 mmol, 2.8 g), 2-(4-(bromomethyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (28 mmol, 9.42 g) and potassium carbonate (55.9 mmol, 9.42 g) were stirred at room temperature in acetonitrile (50 mL) overnight The reaction mixture was diluted with ethyl acetate and filtered through dicalite. The filtrate was concentrated under vacuum and the resulting residue was purified by silica chromatography (eluting with a solvent gradient from dichloromethane to 85/15/1.5 dichloromethane/methanol/ammonia) to afford the title compound (4.55 g). MS (ESI) m/z 357.0 [M+H]+
Reaction SMILES: C([O:9][C@@H:10]1[C@@H:14]([CH2:15][O:16]C(=O)C2C=CC=CC=2)[O:13][C@@H:12]([N:25]2[CH:32]=[CH:31][C:29](=[O:30])[NH:28][C:26]2=[O:27])[C@@H:11]1[O:33][CH3:34])(=O)C1C=CC=CC=1.[OH-].[NH4+]>CO>[CH3:34][O:33][C@@H:11]1[C@H:10]([OH:9])[C@@H:14]([CH2:15][OH:16])[O:13][C@H:12]1[N:25]1[CH:32]=[CH:31][C:29](=[O:30])[NH:28][C:26]1=[O:27]
Reactant: CO[C@@H]1[C@H](OC(=O)c2ccccc2)[C@@H](COC(=O)c2ccccc2)O[C@H]1n1ccc(=O)[nH]c1=O
Agent: [NH4+]
Agent: [OH-]
Solvent: CO
Product: CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(=O)[nH]c1=O
Yield: 8.7 %

Procedure:
A sample of 3', 5'-di-O-benzoyl-2'-O-methyl-uridine (0.80 g, 17 mmoles) was deprotected in a mixture of methanol (65 ml) and concentrated ammonium hydroxide (35 ml) overnight at room temperature. The solution was allowed to evaporate to an oil in the fume hood. The residue was triturated with ether (100 ml). The resulting solid was rinsed with ether and dried to afford 0.38 g (86%) of 2'-O-methyluridine as a white solid, mp 158°-159° C. (lit. C. Chavis, ibid., mp 156°-159° C.). (DMSO-d6): δ3.34 (s, 3H, OCH3), 3.5-3.7 (m, 2H, H-5'), 3.7-3.9 (m, 2H, H-3',4'), 4.14 (m, 1H, H-2'), 5.19 (m, 2H, 3',5'--OH), 5.66 (d, J=8 Hz, 1H, H-5), 5.87 (d, J=5 Hz, 1H, H-1'), 7.95 (d, J=8 Hz, 1H, H-6), 11.35 (br s, 1H, N--H). Anal. calcd for C10H14N2O6 (258.23): C, 46.51; H, 5.46; N, 10.85. Found: C, 46.57; H, 5.49; N, 10.82.
Reaction SMILES: [CH3:1][C:2]1([CH3:28])[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[C:10]([C:15]#[N:16])[CH:11]=3)[C:6]=2[C:5](=[O:17])[C:4]2[CH:18]=[CH:19][C:20]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:21][C:3]1=2.[N:29]1([S:34](N2C=C[N+](C)=C2)(=[O:36])=[O:35])[CH:33]=[CH:32][N:31]=[CH:30]1>>[N:29]1([S:34]([N:25]2[CH2:26][CH2:27][CH:22]([C:20]3[CH:19]=[CH:18][C:4]4[C:5](=[O:17])[C:6]5[C:7]6[C:12](=[CH:11][C:10]([C:15]#[N:16])=[CH:9][CH:8]=6)[NH:13][C:14]=5[C:2]([CH3:28])([CH3:1])[C:3]=4[CH:21]=3)[CH2:23][CH2:24]2)(=[O:36])=[O:35])[CH:33]=[CH:32][N:31]=[CH:30]1
Reactant: C[n+]1ccn(S(=O)(=O)n2ccnc2)c1
Reactant: CC1(C)c2cc(C3CCNCC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
Product: CC1(C)c2cc(C3CCN(S(=O)(=O)n4ccnc4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
Yield: 22.2 %

Procedure:
According to the method disclosed in Journal of Organic Chemistry, 2003, page 115, 6,6-dimethyl-11-oxo-8-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B3-13-2, 10 mg, 0.027 mmol) was reacted with 3-(imidazole-1-sulfonyl)-1-methyl-3H-imidazol-1-ium (19 mg, 2 eq.). After removing the solvent, the residues were purified by liquid chromatography to obtain the title compound (3 mg).
Reaction SMILES: FC(F)(F)C([NH:5][C:6]1[CH:11]=[CH:10][C:9]([S:12](=[O:25])(=[O:24])[NH:13][C:14]2[CH:15]=[CH:16][C:17]3[CH2:21][O:20][B:19]([OH:22])[C:18]=3[CH:23]=2)=[C:8]([CH2:26][CH2:27][C:28](=[O:30])[CH3:29])[CH:7]=1)=O.O[Li].O.Cl>CO.O>[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:13][C:14]2[CH:15]=[CH:16][C:17]3[CH2:21][O:20][B:19]([OH:22])[C:18]=3[CH:23]=2)(=[O:24])=[O:25])=[C:8]([CH2:26][CH2:27][C:28](=[O:30])[CH3:29])[CH:7]=1
Reactant: CC(=O)CCc1cc(NC(=O)C(F)(F)F)ccc1S(=O)(=O)Nc1ccc2c(c1)B(O)OC2
Agent: Cl
Agent: [Li]O
Solvent: O
Solvent: CO
Product: CC(=O)CCc1cc(N)ccc1S(=O)(=O)Nc1ccc2c(c1)B(O)OC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 43.4 %

Procedure:
To a solution of 2,2,2-trifluoro-N-(4-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)-3-(3-oxobutyl)phenyl)acetamide (2 g, 4 mmol) in MeOH (15 mL) and water (15 mL) was added LiOH.H2O (0.93 g, 22 mmol). The mixture was stirred at r.t. overnight. The reaction mixture was concentrated, the residue was purified by pre-HPLC (column: Luna 300×50.0 mm, 10 um; liquid phase: [A-H2O+0.05% TFA; B-MeCN] B %: 12%-42%, 24 min), concentrated, acidified with HCl and freeze-dried to give 4-amino-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-(3-oxobutyl)benzenesulfonamide (650 mg, yield 40%) as HCl salt. 1H NMR: (400 MHz, DMSO-d6). δ 10.00 (s, 1H), 7.40 (d, 1H), 7.21 (d, 1H), 7.11 (d, 1H), 7.09 (d, 1H), 6.36-6.33 (m, 2H), 4.84 (s, 2H), 2.97 (t, 2H), 2.61 (t, 2H), 2.06 (s, 3H).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1)#[CH:2].Br[CH2:11][CH2:12][O:13][CH2:14][CH3:15].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O.CCOC(C)=O>[CH2:12]([O:13][CH2:14][CH2:15][O:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:1]#[CH:2])[CH:4]=1)[CH3:11]
Reactant: CCOCCBr
Reactant: C#Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: C#Cc1cccc(OCCOCC)c1
Temperature: 90 °C
Yield: 96 %

Procedure:
3-Ethynylphenol (1.707 g, 12.45 mmol, 1.0 eq.) and 1-bromo-2-ethoxyethane (1.1 eq.) were taken up in DMF (20 mL), and Cs2CO3 (2.2 eq.) was added. The mixture was heated to 90° C. for 16 hours, and then cooled to room temperature. The mixture was diluted with water (50 mL) and EtOAc (30 mL), and the layers were separated. The organic layers were washed with water (2×50 mL) and brine (3×50 mL), and dried (MgSO4). The resulting residue was purified by chromatography (10% EtOAc/hexanes) to yield 1-(2-ethoxyethoxy)-3-ethynylbenzene as an oil (2.63 g, 96%).
Reaction SMILES: C[O:2][C:3]([C@H:5]1[C@H:13]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=2[OH:22])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:23][CH2:24][CH2:25][CH3:26])[CH:11]=2)[C@@H:6]1[C:27]1[CH:32]=[CH:31][C:30]2[O:33][CH2:34][O:35][C:29]=2[CH:28]=1)=[O:4].[OH-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.CO.O.COC(C)(C)C>[CH2:34]1[O:33][C:30]2[CH:31]=[CH:32][C:27]([C@H:6]3[C:7]4[C:12](=[CH:11][C:10]([O:23][CH2:24][CH2:25][CH3:26])=[CH:9][CH:8]=4)[C@@H:13]([C:14]4[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=4[OH:22])[C@@H:5]3[C:3]([OH:4])=[O:2])=[CH:28][C:29]=2[O:35]1
Reactant: CCCOc1ccc2c(c1)[C@@H](c1ccc(OC)cc1O)[C@H](C(=O)OC)[C@H]2c1ccc2c(c1)OCO2
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: CCCOc1ccc2c(c1)[C@@H](c1ccc(OC)cc1O)[C@H](C(=O)O)[C@H]2c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
Methyl-(1S,2R,3S)-1-(3,4-methylenedioxyphenyl)-3-(4-methoxy-2-hydroxyphenyl)-5-propoxyindane-2-carboxylate (0.3183 g, 0.667 mmoles) was dissolved in 2 mL of tetrahydrofuran and 4 mL of methanol. A solution of lithium hydroxide (0.1402 g, 3.34 mmoles) in 1.8 mL of water was added over a period in one portion. The reaction mixture was heated to reflux temperature while monitoring the reaction progress by HPLC. After 22 hours at reflux, HPLC analysis indicated that the reaction was complete. The reaction mixture was cooled to 25° C., then diluted with t-butyl methyl ether (5 mL). A 5% solution of citric acid (5 mL) was added and the mixture was stirred for five minutes. The layers were separated and the aqueous layer was extracted with 10 mL of t-butyl methyl ether. The combined organic layers were washed twice with water and filtered. The solution was concentrated under reduced pressure to afford the title compound as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([CH2:11][C:12]([N:14]([CH3:16])[CH3:15])=[O:13])[CH2:9][CH2:10][C:4]=2[CH:3]=1.[Cl:19][C:20]1[C:21]([NH:30][C:31]2[C:36]([Cl:37])=[CH:35][N:34]=[C:33](Cl)[N:32]=2)=[C:22]([CH:27]=[CH:28][CH:29]=1)[C:23]([NH:25][CH3:26])=[O:24]>>[Cl:19][C:20]1[C:21]([NH:30][C:31]2[C:36]([Cl:37])=[CH:35][N:34]=[C:33]([NH:1][C:2]3[CH:18]=[CH:17][C:5]4[CH2:6][CH2:7][N:8]([CH2:11][C:12](=[O:13])[N:14]([CH3:15])[CH3:16])[CH2:9][CH2:10][C:4]=4[CH:3]=3)[N:32]=2)=[C:22]([CH:27]=[CH:28][CH:29]=1)[C:23]([NH:25][CH3:26])=[O:24]
Reactant: CNC(=O)c1cccc(Cl)c1Nc1nc(Cl)ncc1Cl
Reactant: CN(C)C(=O)CN1CCc2ccc(N)cc2CC1
Product: CNC(=O)c1cccc(Cl)c1Nc1nc(Nc2ccc3c(c2)CCN(CC(=O)N(C)C)CC3)ncc1Cl

Procedure:
3-Chloro-2-[5-chloro-2-(3-dimethylcarbamoylmethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide was prepared from 2-(7-amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide and 3-chloro-2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide in an analogous manner to Example 308c. Product isolated as a yellow foam (26 mg, 12%). LCMS (m/e) 542 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.09 (s, 1H), 7.86 (s, 1H), 7.60 (d, 1H, J=8.0 Hz), 7.47 (d, 1H, J=7.7 Hz), 7.34-7.26 (m, 1H), 7.12 (s, 1H), 7.05-6.99 (m, 1H), 6.91-6.83 (m, 2H), 6.06-5.97 (m, 1H), 3.29 (s, 2H), 3.14 (s, 3H), 2.99 (s, 3H), 2.90-2.84 (m, 2H), 2.77 (d, 3H, J=4.9 Hz), 2.77-2.71 (m, 2H), 2.70-2.62 (m, 4H).