Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([S:12]([O-:15])(=[O:14])=[O:13])=[CH:4][CH:3]=1.[Na+].[N:17]([O-])=O.[Na+].OS(O)(=O)=O.Cl[Sn]Cl>O.Cl>[NH:1]([C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([S:12]([OH:15])(=[O:13])=[O:14])=[CH:4][CH:3]=1)[NH2:17]
Reactant: Nc1ccc(S(=O)(=O)[O-])c2ccccc12
Reactant: O=N[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Agent: O=S(=O)(O)O
Solvent: O
Product: NNc1ccc(S(=O)(=O)O)c2ccccc12
Reaction time: 1.5 h
Yield: 58.8 %

Procedure:
A solution of sodium 4-aminonaphthalene-1-sulfonate (2.45 g, 10 mmol) in H2O (15 mL) was added a solution of NaNO2 (0.70 g, 10 mmol) in H2O (2 mL) at 10-15° C. The solution was then added to a cold solution of conc. H2SO4 (0.54 g, 5.5 mmol) in 0.5 mL of H2O. The temperature was maintained below 10° C. and the mixture was stirred for 1.5 h after the addition was complete. The mixture was then added dropwise to a cold solution of SnCl2 (3.8 g, 17 mmol) in 2.5 mL of conc. HCl and 1.5 ml of H2O. The reaction temperature was kept below 10° C. and allowed to sit onemoght. It was filtered and washed thoroughly with H2O. The cake was removed twice from the Buchner funnel and suspended in H2O and filtered. The solid obtained was dried under vacuum to give 1.4 g of 4-hydrazinylnaphthalene-1-sulfonic acid (59%). The material was used directly for next step. A solution of 4-hydrazinylnaphthalene-1-sulfonic acid (0.7 g, 2.9 mmol) in 3 ml of HOAc was added 3-methylbutan-2-one (0.5 ml, 1.5 eq), NaOAc (0.47 g, 2.0 eq.). The mixture was stirred at 110° C. for 3.5 h. After cooling and addition of ether, the precipitate was filtered to give 700 mg. The solid was dissolved in DCM and purified by flash chromatography on SiO2 using 10% MeOH in DCM to give 273 mg of product. The mother liquor was concentrated and was also purified by flash chromatography on silica gel to give additional 372 mg of product. The overall yield was 77%. 1H NMR (DMSO) δppm: 8.8 (dd, 1H), 8.4 (dd, 1H), 8.0 (s, 1H), 7.5 (m, 2H), 3.1 (s, 5H), 2.3 (s, 4H), 1.3 (s, 6H). LC-MS: 288.2 [M−H].
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH2:11])=[N:8][C:7]=1[CH3:12])=[O:5])[CH3:2].[C:13]([O:17][C:18]([O:20]C(OC(C)(C)C)=O)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CN(C)C1C=CN=CC=1.O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][O:20][C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])=[N:8][C:7]=1[CH3:12])=[O:5])[CH3:2]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: CCOC(=O)c1sc(N)nc1C
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CCOC(=O)c1sc(NOC(=O)OC(C)(C)C)nc1C
Reaction time: 18 h
Yield: 66.1 %

Procedure:
A suspension of ethyl-2-amino-4-methyl-thiazole-5-carboxylate (18.6 g, 100 mmol), di-t-butyldicarbonate (26.2 g, 120 mmol) and 4-dimethylaminopyridine (800 mg, 6.55 mmol) in dry tetrahydrofuran (300 mL) was stirred under nitrogen for 18 h. The solvent was evaporated in vacuo. The residue was suspended in dichloromethane (1 L) and filtered through a pad of celite. The filtrate was washed with 1 N aqueous HCl solution (300 mL, 2×), water and brine, dried (MgSO4), and concentrated in vacuo. The residue was triturated with hexanes. The solid was filtered and dried in vacuo to obtain the title compound (20 g, 72%) as a tan solid.
Reaction SMILES: [CH2:1](O)[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].S(Cl)(C)(=O)=O.O.[N-:28]=[N+:29]=[N-:30].[Na+]>N1C=CC=CC=1.CN(C=O)C>[CH2:1]([N:28]=[N+:29]=[N-:30])[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: [N-]=[N+]=[N-]
Reactant: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCO
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: O
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCN=[N+]=[N-]
Temperature: 90 °C
Reaction time: 5 h
Yield: 72.7 %

Procedure:
To a magnetically stirred solution of 50 mg (0.17 mmol) of arachidonyl alcohol in 1 mL of pyridine was added 29.2 mg (0.225 mmol) of mesyl chloride at 0° C. After stirring for 5 hours, the reaction mixture was poured into 2 mL of cold water and extracted with diethyl ether (2×4 mL). The combined ether extracts were washed with 1 N sulfuric acid and saturated sodium bicarbonate solution and evaporated in vacuo. The crude mesylate was dissolved in 2 mL of anhydrous DMF, and then a solution of 6.5 mg (0.85 mmol) of sodium azide in 4 mL of anhydrous DMF was added at room temperature. The reaction mixture was heated to 90° C. for 24 hours behind a safety shield. The mixture was cooled to room temperature, inorganic material was filtered off, and the filtrate was poured into 1 mL of cold water. Extraction with diethyl ether (2×6 mL), drying (MgSO4), and evaporation gave an oily residue which was chromatographed on silica gel (petroleum ether) to afford 39 mg (73%) of arachidonyl azide as a colorless oil: 1H NMR (200 MHZ, CDCl3) δ 5.38 (m, 8H), 3.27 (t, J=6 Hz, 2H), 2.81 (m, 6H), 2.11–2.01 (m, 4H), 1.62 (m, 2H), 1.48–1.25 (m, 6H), 0.89 (t, J=7 Hz, 3H).
Reaction SMILES: Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@:24]([OH:28])([CH3:27])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:29]1[CH:34]=[C:33](B(O)O)[CH:32]=[N:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>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.CCO.O>[OH:28][C@@:24]1([CH3:27])[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:33]3[CH:34]=[N:29][CH:30]=[N:31][CH:32]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]1
Reactant: C[C@]1(O)CCN(c2ncc(C(=O)Nc3ccc(OC(F)(F)F)cc3)cc2Br)C1
Reactant: OB(O)c1cncnc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: COCCOC
Product: C[C@]1(O)CCN(c2ncc(C(=O)Nc3ccc(OC(F)(F)F)cc3)cc2-c2cncnc2)C1

Procedure:
(S)-5-Bromo-6-(3-hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 65.1, 60 mg, 0.130 mmol), pyrimidin-5-ylboronic acid (32.3 mg, 0.261 mmol), Pd(PPh3)2Cl2 (9.15 mg, 0.013 mmol) and Na2CO3 (41.5 mg, 0.391 mmol) were added to a MW vial and treated with a mixture of DME (553 μL), water (158 μL) and EtOH (79 μL). The vial was sealed, evacuated/purged with argon and was subjected to MW irradiation at 120° C. for 10 min. The RM was diluted with DME (2 mL), treated with Si-Thiol (1.44 mmol/g, 45.3 mg, 0.065 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column Silica, from 23% to 28% in 6 min.) to yield the title compound as a white amorphous solid. UPLC-MS (Condition 3) tR=0.94 min, m/z=460.4 [M+H]+, m/z=458.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.20 (s, 3H) 1.66-1.84 (m, 2H) 2.95 (d, J=11.80 Hz, 1H) 3.02 (d, J=11.17 Hz, 1H) 3.17-3.26 (m, 1H) 3.37-3.47 (m, 1H) 4.75 (s, 1H) 7.35 (d, J=8.53 Hz, 2H) 7.85 (d, J=9.16 Hz, 2H) 8.10 (d, J=2.38 Hz, 1H) 8.78 (d, J=2.13 Hz, 1H) 8.89 (s, 2H) 9.16-9.24 (m, 1H) 10.18 (s, 1H).
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:21])[N:7]3[CH2:20][CH2:19][C:14]4([O:18][CH2:17][CH2:16][O:15]4)[CH2:13][CH2:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1.[C:22]([Si:24]([CH3:27])([CH3:26])[CH3:25])#[CH:23].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu]I>[CH3:25][Si:24]([C:22]#[C:23][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:21])[N:7]3[CH2:20][CH2:19][C:14]4([O:18][CH2:17][CH2:16][O:15]4)[CH2:13][CH2:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1)([CH3:27])[CH3:26]
Reactant: O=c1c2ccc(Br)cc2nc2n1CCC1(CC2)OCCO1
Reactant: C#C[Si](C)(C)C
Agent: [Cu]I
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: C[Si](C)(C)C#Cc1ccc2c(=O)n3c(nc2c1)CCC1(CC3)OCCO1
Temperature: 25 °C

Procedure:
A solution of 3-bromo-9,10-dihydro-6H-spiro[azepino[2,1-b]quinazoline-8,2′-[1,3]dioxolan]-12(7H)-one (1.74 g, 4.96 mmol, 1 equiv), ethynyltrimethylsilane (972 mg, 9.92 mmol, 2 equiv), Pd(OAc)2 (223.2 mg, 0.992 mmol, 0.2 equiv), PPh3 (1.04 g, 3.96 mmol, 0.8 equiv), CuI (189 mg, 0.992 mmol, 0.2 equiv) and Et3N (1.3 mL) in DMF (50 mL) was stirred in a sealed tube at 70° C. for 3.5 hours. After it was cooled to room temperature, the reaction mixture was diluted with H2O and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate, then concentrated under reduced pressure. The product was obtained by silica gel chromatography purification.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)[CH:14]=[C:15]([OH:16])[C:7]1=2)[CH3:2].[C:25]([O:29][C:30](=[O:36])[NH:31][CH2:32][CH2:33]CBr)([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)[CH:14]=[C:15]([O:16][CH2:33][CH2:32][NH:31][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:36])[C:7]1=2)[CH3:2]
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3cnccn3)cc(O)c21
Reactant: CC(C)(C)OC(=O)NCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)CC1OB(O)c2cc(Oc3cnccn3)cc(OCCNC(=O)OC(C)(C)C)c21
Yield: 41.5 %

Procedure:
A solution of [1,4-dihydroxy-6-(pyrazin-2-yloxy)-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (from Step 7.9, 90 mg, 0.27 mmol) in DMF (10 mL) was treated with (3-bromo-propyl)-carbamic acid tert-butyl ester (92 mg, 0.41 mmol) and potassium carbonate (187 mg, 1.35 mmol) at 50° C. overnight. The reaction was concentrated to dryness. The residue was diluted with MeOH/H2O and the mixture was adjusted pH to 3. The solution was purified by preparative HPLC to afford the title compound as a white solid (53 mg). MS calcd for (C22H28BN3O8+H-Boc)+: 374.2. MS found: (M+H-Boc)+=374.2.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[C:12](=[O:32])[NH:13][C:14](=[O:31])[C:15]=2[C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:25][CH2:26][CH2:27][S:28]([CH3:30])=[O:29])[CH:17]=2)=[CH:3]1.ClC1C=CC=C(C(OO)=[O:41])C=1>ClCCl>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[C:12](=[O:32])[NH:13][C:14](=[O:31])[C:15]=2[C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:25][CH2:26][CH2:27][S:28]([CH3:30])(=[O:41])=[O:29])[CH:17]=2)=[CH:3]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cn1cc(C2=C(c3cn(CCCS(C)=O)c4ccccc34)C(=O)NC2=O)c2ccccc21
Solvent: ClCCl
Product: Cn1cc(C2=C(c3cn(CCCS(C)(=O)=O)c4ccccc34)C(=O)NC2=O)c2ccccc21
Reaction time: 2 h
Yield: 26.8 %

Procedure:
90 mg of the product of Example 97 in 5 ml of dichloromethane were treated with 60 mg of 85% metachloroperbenzoic acid in 5 ml of dichloromethane. The solution was stirred for 2 hours and then washed with aqueous sodium bicarbonate. The solution was dried and concentrated. Chromatography of the residue on silica gel with dichloromethane/ethyl acetate (1:1) and recrystallization from ethyl acetate/hexane gave 25 mg of 3-(1-methyl-3-indolyl)-4-[1-(3-methylsulphonylpropyl)-3-indolyl]-1H-pyrrole-2,5-dione, m.p. 225°-227° C.
Reaction SMILES: [NH2:1][C:2]1[C:6]([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:8])=[CH:5][NH:4][N:3]=1.[H-].[Na+].[CH2:17](I)[CH3:18]>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:6]([C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:8])=[CH:5][N:4]([CH2:17][CH3:18])[N:3]=1
Reactant: Nc1n[nH]cc1C(=O)c1ccccc1
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCn1cc(C(=O)c2ccccc2)c(N)n1
Reaction time: 1 h

Procedure:
To a vigorously stirring solution of (3-amino-1H-pyrazol-4-yl)-phenyl-methanone (0.1 g, 0.53 mmol) in dry DMF at RT is added sodium hydride (0.023 g, 0.57 mmol). After 1 h, ethyl iodide (0.042 mL, 0.53 mmol) is added and stirring is continued for 4 h. The reaction mixture is diluted with ethyl acetate, washed with water, brine and dried over anhydrous sodium sulfate. The organic filtrate is concentrated and the crude is chromatographed on silica gel using 50% ethyl acetate in hexanes to provide (3-amino-1-ethyl-1H-pyrazol-4-yl)-phenyl-methanone.
Reaction SMILES: [NH2:1][C@@H:2]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:15])([CH3:14])[C@H:3]1[OH:16].[CH:17]1[CH:22]=[CH:21][C:20]([O:23][C:24](OC2C=CC=CC=2)=[N:25][C:26]#[N:27])=[CH:19][CH:18]=1>C(O)(C)C>[C:26]([N:25]=[C:24]([NH:1][C@@H:2]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:14])([CH3:15])[C@H:3]1[OH:16])[O:23][C:20]1[CH:21]=[CH:22][CH:17]=[CH:18][CH:19]=1)#[N:27]
Reactant: CC1(C)Oc2ccc(C#N)cc2[C@@H](N)[C@@H]1O
Reactant: N#CN=C(Oc1ccccc1)Oc1ccccc1
Solvent: CC(C)O
Product: CC1(C)Oc2ccc(C#N)cc2[C@@H](NC(=NC#N)Oc2ccccc2)[C@@H]1O
Temperature: 25 °C
Reaction time: 16 h
Yield: 50.4 %

Procedure:
To a solution of (trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (prepared according to Evans et al., J. Med. Chem., 1983, 26, 1582 and J. Med. Chem., 1986, 29, 2194) (5.0 g, 23 mmol) in isopropanol (50 mL), diphenylcyanocarbonimidate (5.5 g, 25 mmol) was added at room temperature and the reaction mixture was allowed to stir at room temperature for 16 hours. Most of the isopropanol was evaporated and the residue was dissolved in ethyl acetate. The resulting solution was washed successively with 10% citric acid, 1N sodium hydroxide solution and brine. It was dried over anhydrous magnesium sulfate, concentrated and the residue was crystallized from chloroform-isopropyl ether to yield the title A compound (4.2 g) as a colorless solid, m.p. 186°-188° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][C:7]2[CH2:8][CH2:9][NH:10][CH2:11][C:12]=2[CH:13]=1)([O-])=O.C(O)CCCC>CO.[Pd]>[N:6]1[C:7]2[C:12](=[CH:11][N:10]=[CH:9][CH:8]=2)[CH:13]=[C:4]([NH2:1])[CH:5]=1
Reactant: O=[N+]([O-])c1cnc2c(c1)CNCC2
Agent: [Pd]
Solvent: CO
Solvent: CCCCCO
Product: Nc1cnc2ccncc2c1
Temperature: 180 °C
Reaction time: 1 h

Procedure:
3-Nitro-5,6,7,8-tetrahydro-[1,6]naphthyridine (1 g, 5.6 mmol), pentanol (2 mL) and Pd/C (300 mg) were placed in a microwave reaction vessel and stirred under microwave irradiation at 180° C. for 1 h. After cooling, the mixture was diluted with MeOH and filtered through a pad of Celite. The solvent was removed and the crude was purified by flash column chromatography to give the desired title compound as a yellow solid. MS (ES+): 146.2 (M+H)+. Calc'd for C8H7N3—145.06.
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[C:13]([O:17][C:18](=[O:29])[CH2:19][CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])([CH3:16])([CH3:15])[CH3:14].[Br:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37]Br)=[C:33]([F:39])[CH:32]=1>C1COCC1>[C:13]([O:17][C:18](=[O:29])[CH:19]([CH2:37][C:34]1[CH:35]=[CH:36][C:31]([Br:30])=[CH:32][C:33]=1[F:39])[CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)(C)OC(=O)CCNC(=O)OC(C)(C)C
Reactant: Fc1cc(Br)ccc1CBr
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCC(Cc1ccc(Br)cc1F)C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 76.2 %

Procedure:
To a stirred solution of diisopropyl amine (1.3 mL, 9.0 mmol) in THF (20 mL) was added n-BuLi (1.6 M solution in hexanes, 5.6 mL, 9.0 mmol) at 0° C. The reaction was stirred at 0° C. for 15 minutes and then cooled to −78° C. A solution of 3-tert-butoxycarbonylamino-propionic acid tert-butyl ester (1.0 g, 4.1 mmol) in THF (5 mL) was added dropwise. The mixture was stirred at −78° C. for 2 hours. A solution of 4-Bromo-1-bromomethyl-2-fluoro-benzene (1.3 g, 4.9 mmol) in THF (4 mL) was added dropwise. After completion, the dry-ice bath was removed and the reaction was warmed to 0° C. in an ice bath. After stirring at 0° C. for 30 minutes, the reaction was poured into saturated NH4Cl aqueous solution. The organic layer was separated. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (hexane:EtOAc, 20:1 to 5:1) to give 2-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid tert-butyl ester (1.35 g, 77%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.20 (d, J=8.0 Hz, 2H), 7.08 (t, J=8.0 Hz, 1H), 4.86 (m, 1H), 3.28 (m, 2H), 2.92 (m, 3H), 1.43 (s, 9H), 1.36 (s, 9H).
Reaction SMILES: C([NH:11][CH2:12][C:13](=[O:37])[CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29]CC1C=CC=CC=1)=[O:28])=[O:17])(OCC1C=CC=CC=1)=O.[ClH:38].[H][H]>[Pd].CC(O)C>[ClH:38].[NH2:11][CH2:12][C:13](=[O:37])[CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])=[O:17]
Reactant: [H][H]
Reactant: O=C(CCC(=O)OCCCCCCCCC(=O)OCc1ccccc1)CNC(=O)OCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CC(C)O
Product: NCC(=O)CCC(=O)OCCCCCCCCC(=O)O
Yield: 61.8 %

Procedure:
This compound was prepared from the product of 11c (1.4 g; 2.7 mmol), 12 M HCl (0.25 mL; 3.0 mmol), 10% Pd/C (100 mg), hydrogen gas, and 2-propanol (25 mL) using the procedure in Example 8d. 0.54 g (62%) product was obtained (white solid).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]([NH:11]C=O)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[O:14][CH2:15][CH:16]1[CH2:21][O:20][C:19]([CH3:23])([CH3:22])[O:18][CH2:17]1.[C:24](O)(=[O:26])C>C[O-].[Na+].CO>[NH2:11][C:9]1[N:8]=[C:7]2[C:3]([N:4]=[CH:5][N:6]2[O:14][CH2:15][CH:16]2[CH2:17][O:18][C:19]([CH3:22])([CH3:23])[O:20][CH2:21]2)=[C:2]([O:26][CH3:24])[N:10]=1
Reactant: CC(=O)O
Reactant: CC1(C)OCC(COn2cnc3c(Cl)nc(NC=O)nc32)CO1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1nc(N)nc2c1ncn2OCC1COC(C)(C)OC1
Yield: 69 %

Procedure:
6-Chloro-9-(2,2-dimethyl-1,3-dioxan-5-ylmethoxy)-2-formamidopurine (0.5 g, 1.46 mmol) in 1.2M sodium methoxide in methanol (3.38 ml) and methanol (5 ml) was heated at reflux temperature for 1.5 hours and then cooled. Acetic acid (0.16 ml) was added and the solution evaporated to dryness. The residue was suspended in water and extracted with ethyl acetate (2×50 ml). The combined ethyl acetate extracts were washed with water, dried (magnesium sulphate) and evaporated under reduced pressure. Chromatography on silica gel (eluted with chloroform-ethanol, 100:1) gave the title compound (310 mg, 69%). 1R: υmax (KBr) 3397, 3208, 1640, 1616, 1581, 1480, 1390 cm-1. 1H NMR: δH [(CD3)2SO] 1.32(3H,s,CH3), 1.35(3H,s,CH3), 2.00(1H,m,CH), 3.77(2H,dd, J=11.8, 6.1 Hz, 2×H(ax), 3.9 (3H,s,OCH3), 3.99 (2H,dd,J=11.8, 4.1 Hz, 2×H(eq)), 4.36(2H,d, J=6.8 Hz, CH2ON), 6.60(2H,br.s, D2O exchangeable, NH2), 8.14(1H,s,H-8). Found: C, 49.30; H, 6.12; N, 22.03%; M+ 309.1455. C13H19N5O4 0.5H2O requires: C, 49.04; H, 6.34; N, 22.00%; M+ 309.1437.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([S:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:18])=[C:15]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[S:14][C:13]=2[CH:30]=1)C1C=CC=CC=1.C1(SC)C=CC=CC=1>FC(F)(F)C(O)=O>[OH:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([S:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:18])=[C:15]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[S:14][C:13]=2[CH:30]=1
Reactant: CCOC(=O)c1sc2cc(OCc3ccccc3)ccc2c1S(=O)c1ccccc1
Solvent: CSc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)c1sc2cc(O)ccc2c1S(=O)c1ccccc1
Yield: 78.6 %

Procedure:
Trifluoroacetic acid (50 ml) was added to a stirred mixture of ethyl 6-(benzyloxy)-3-(phenylsulfinyl)benzo[b]thiophene-2-carboxylate (Example 31, 4.9 g, 11.2 mmol) and methyl phenyl sulfide (5.2 ml, 45 mmol) at ambient temperature under a nitrogen atmosphere. After 20 hours the solvents were removed under reduced pressure, and the residue was azeotroped using toluene. The residue was flash chromatographed on silica gel using 2% ethanol in dichloromethane as eluant. The isolated product was crystallised from diisopropyl ether to give the title compound as a colourless solid (3.05 g).
Reaction SMILES: [CH3:1][N:2]([CH3:29])[C:3]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:8][CH2:7][C:6]([CH2:10][C@H:11]([CH3:22])[CH2:12][C:13]#[C:14][Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17])([OH:9])[CH2:5][CH2:4]1.I[C:31]1[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=1[NH2:33].C(=O)([O-])[O-].[Na+].[Na+]>O=O.O.C(C1C=CC=C(C(C)C)C=1N1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C1=[Pd-2](Cl)C1C(Cl)=CC=CN=1)(C)C>[CH3:29][N:2]([CH3:1])[C:3]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:8][CH2:7][C:6]([CH2:10][C@H:11]([CH3:22])[CH2:12][C:13]2[C:34]3[C:32](=[CH:31][CH:37]=[CH:36][CH:35]=3)[NH:33][C:14]=2[Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17])([OH:9])[CH2:5][CH2:4]1
Reactant: CC[Si](C#CC[C@@H](C)CC1(O)CCC(c2ccccc2)(N(C)C)CC1)(CC)CC
Reactant: Nc1ccccc1I
Agent: CC(C)c1cccc(C(C)C)c1-n1ccn(-c2c(C(C)C)cccc2C(C)C)c1=[Pd-2](Cl)c1ncccc1Cl
Agent: O=C([O-])[O-]
Agent: O=O
Solvent: O
Product: CC[Si](CC)(CC)c1[nH]c2ccccc2c1C[C@@H](C)CC1(O)CCC(c2ccccc2)(N(C)C)CC1

Procedure:
A solution of (R)-4-dimethylamino-1-(2-methyl-5-(triethylsilyl)pent-4-inyl)-4-phenylcyclohexanol (106 mg, 0.25 mmol), [1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene]-(3-chloropyridyl)palladium(II)-chloride (PEPPSI, 34 mg, 0.05 mmol), 2-iodoaniline (68 mg, 0.31 mmol) and sodium carbonate (136 mg, 1.28 mmol) in oxygen- and water-free N,N-dimethylformamide (5 mL) was stirred for 18 h at 100° C. The reaction mixture was concentrated to low volume in a vacuum, the residue mixed with toluol several times and the mixture concentrated to low volume again in each case. This residue was distributed between water and ethyl acetate (10 mL each), the phases were separated and the aqueous phase extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with 1 M sodium thiosulphate solution and water (10 mL each), dried with sodium sulphate, filtered and concentrated to low volume in a vacuum. The raw product was purified by flash chromatography (10 g, 20×1.5 cm) with ethyl acetate/cyclohexane (1:2).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[C:10](=O)[CH2:9][CH2:8][CH2:7][C:5]=2[N:6]=1.CC1C=CC(S([CH2:22][N+:23]#[C-])(=O)=O)=CC=1.C(O)C.CC([O-])(C)C.[K+]>COCCOC>[CH3:1][C:2]1[S:3][C:4]2[CH:10]([C:22]#[N:23])[CH2:9][CH2:8][CH2:7][C:5]=2[N:6]=1
Reactant: Cc1nc2c(s1)C(=O)CCC2
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: CCO
Product: Cc1nc2c(s1)C(C#N)CCC2
Temperature: 25 °C

Procedure:
To a stirred and cooled solution of 5,6-dihydro-2-methylbenzo[d]thiazol-7(4H)-one (1.67 g, 10 mmol) and TOSMIC (2.5 g, 13 mmol) in a mixture of DME (25 mL) and absolute ethanol (25 mL) was added solid t-BuOK (2.8 g, 24 mmol) portionwise while keeping the reaction temperature between 5 and 10° C. The resulting mixture was stirred at room temperature for 30 minutes and at 30-45° C. for 30 minutes. The resulting suspension was cooled to room temperature. The precipitate (TosK) was removed by filtration and rinsed with DME. The combined DME solutions were concentrated under reduced pressure to give the crude product, which was purified by column chromatography.