Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:16]2[CH:17]=[N:18][N:19]([CH:21]3[CH2:26][CH2:25][N:24]([C:27](=[O:29])[CH3:28])[CH2:23][CH2:22]3)[CH:20]=2)=[C:6]2[CH:10]=[C:9]([C:11]3[CH2:15][CH2:14][CH2:13][CH:12]=3)[O:8][C:7]=12>C1COCC1.[Pd]>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:16]2[CH:17]=[N:18][N:19]([CH:21]3[CH2:26][CH2:25][N:24]([C:27](=[O:29])[CH3:28])[CH2:23][CH2:22]3)[CH:20]=2)=[C:6]2[CH:10]=[C:9]([CH:11]3[CH2:12][CH2:13][CH2:14][CH2:15]3)[O:8][C:7]=12
Reactant: CC(=O)N1CCC(n2cc(-c3cnc(N)c4oc(C5=CCCC5)cc34)cn2)CC1
Agent: [Pd]
Solvent: C1CCOC1
Product: CC(=O)N1CCC(n2cc(-c3cnc(N)c4oc(C5CCCC5)cc34)cn2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 40.7 %

Procedure:
1-{4-[4-(7-Amino-2-cyclopent-1-enyl-furo[2,3-c]pyridin-4-yl)-pyrazol-1-yl]-piperidin-1-yl}-ethanone (80 mg, 0.2 mmol) and10% Pd/C (20 mg) were suspended in dry THF (30 mL) and the solution was stirred at rt under a hydrogen balloon overnight. The Pd/C was filtered and the filtrate was concentrated. The residue was purified by preparative TLC (5:1 DCM:MeOH) to afford 32 mg (40%) of the title compound. 1H NMR (400 MHz, CD3OD): δ 8.03 (d, J=0.8 Hz, 1H), 7.80-7.81 (d, J=0.8 Hz, 1H), 7.79 (s, 1H), 6.70 (s, 1H), 4.62-4.70 (m, 1H), 4.49-4.51 (m, 1H), 4.10-4.22 (m, 1H), 3.31-3.33 (m, 1H), 2.76-2.85 (m, 1H), 2.15-2.20 (m, 2H), 2.14 (s, 3H), 2.08-2.14 (m, 2H), 1.92-2.08 (m, 2H), 1.85-1.88 (m, 5H), 1.70-1.78 (m, 2H); MS (ESI): 394.16 [M+H]+; HPLC tR=2.40 min (ZQ3: polar—4 min).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[NH:21][C:20](=[O:22])[C:19]3[C:14](=[CH:15][C:16]([O:25][CH3:26])=[CH:17][C:18]=3[O:23][CH3:24])[N:13]=2)=[CH:7][C:6]=1[CH3:27].[CH3:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:24][O:23][C:18]1[CH:17]=[C:16]([O:25][CH3:26])[CH:15]=[C:14]2[C:19]=1[C:20](=[O:22])[NH:21][C:12]([C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([O:4][CH2:3][CH2:2][NH:1][S:36]([C:33]3[CH:32]=[CH:31][C:30]([O:29][CH3:28])=[CH:35][CH:34]=3)(=[O:38])=[O:37])=[C:6]([CH3:27])[CH:7]=1)=[N:13]2
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCN)c(C)c3)nc2c1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(S(=O)(=O)NCCOc2c(C)cc(-c3nc4cc(OC)cc(OC)c4c(=O)[nH]3)cc2C)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 52.6 %

Procedure:
A mixture of 2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.060 g, 0.162 mmol), 4-methoxybenzenesulfonyl chloride (0.044 mg, 0.211 mmol), and triethylamine (29.4 μL, 0.211 mmol) in CH2Cl2 (812 μL) was stirred at room temperature for 3 h. The mixture was chromatographed directly on silica gel to yield N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-4-methoxybenzenesulfonamide (0.046 g, 53%) as a white solid after lyophilization from MeCN/H2O. Selected data: 1H NMR (300 MHz, DMSO-d6) δ ppm 11.81 (s, 1H), 7.88 (s, 2H), 7.83-7.73 (m, 3H), 7.17-7.07 (m, 2H), 6.73 (d, J=2.31 Hz, 1H), 6.52 (d, J=2.29 Hz, 1H), 3.91-3.75 (m, 11H), 3.12 (q, J=5.75 Hz, 2H), 2.24 (s, 6H); MS (APCI) m/z 540 [M+H]+.
Reaction SMILES: [Cl-].[Ca+2:2].[Cl-].[P:4]([OH:8])([O-:7])([O-:6])=[O:5].[Na+].[Na+].[OH-].[Li+]>>[OH-:5].[O-:6][P:4]([O-:8])([O-:7])=[O:5].[O-:6][P:4]([O-:8])([O-:7])=[O:5].[O-:6][P:4]([O-:8])([O-:7])=[O:5].[Ca+2:2].[Ca+2:2].[Ca+2:2].[Ca+2:2].[Ca+2:2]
Reactant: O=P([O-])([O-])O
Agent: [Ca+2]
Agent: [Cl-]
Agent: [Li+]
Product: O=P([O-])([O-])[O-]

Procedure:
Reaction was carried out under the same conditions as in Example 2 except that concentration of an aqueous calcium chloride solution and that of an aqueous disodium phosphate solution were changed to 1 mol/l and that of an aqueous lithium hydroxide solution was changed to 2 mol/l, thereby to obtain hydroxylapatite in the form of hexagonal prismatic crystal [referred to as "hydroxylapatite (E)"].
Reaction SMILES: [Mg].Br[CH:3]1[CH2:6][CH2:5][CH2:4]1.BrCCBr.Br[C:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[N:14]([S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH:13]=1>C1COCC1.CCOCC>[CH:3]1([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[CH:18][CH:19]=3)[N:14]([S:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)(=[O:23])=[O:22])[CH:13]=2)[CH2:6][CH2:5][CH2:4]1
Reactant: BrC1CCC1
Reactant: O=S(=O)(c1ccccc1)n1cc(Br)c2cccnc21
Agent: [Mg]
Solvent: BrCCBr
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=S(=O)(c1ccccc1)n1cc(C2CCC2)c2cccnc21
Temperature: 25 °C
Yield: 19.5 %

Procedure:
A round bottom flask under a nitrogen atmosphere was charged with magnesium turnings (155 mg, 6.38 mmol) and dry ether (5 mL). Bromocyclobutane (340 mg, 2.52 mmol) was added, followed by 1,2-dibromoethane (50 μL) and refluxing was observed after a few minutes of stirring. This mixture was then warmed back to reflux for 5 hours and then allowed to cool to room temperature. The Grignard reagent was then added to a THF solution (5 mL) of 3-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (250 mg, 0.74 mmol) and NiCl2(dppf) (10 mg, 0.015 mmol). The mixture was heated at reflux for 16 hours and then allowed to cool to room temperature. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with EtOAc (2×). The extracts were dried over sodium sulfate and concentrated. Flash 40 Biotage (40M cartridge, 3:1 hexane:EtOAc) afforded 3-cyclobutyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (45 mg, 19%). m/z (APCI-pos) M+1=313.1.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:15]([O:19][C:20]([NH:22][C@@:23]1([C:34]([OH:36])=[O:35])[CH2:30][C:27]2([CH2:29][CH2:28]2)[C@@H:26]2[C@H:24]1[C@H:25]2[C:31]([OH:33])=[O:32])=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C)C=O>[C:15]([O:19][C:20]([NH:22][C@@:23]1([C:34]([O:36][CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:35])[CH2:30][C:27]2([CH2:29][CH2:28]2)[C@@H:26]2[C@H:24]1[C@H:25]2[C:31]([O:33][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:32])=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: BrCc1ccccc1
Reactant: CC(C)(C)OC(=O)N[C@@]1(C(=O)O)CC2(CC2)[C@H]2[C@H](C(=O)O)[C@H]21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@]1(C(=O)OCc2ccccc2)CC2(CC2)[C@H]2[C@H](C(=O)OCc3ccccc3)[C@H]21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 73.1 %

Procedure:
Add cesium carbonate (0.24 g, 730.7 μmol) and benzyl bromide (87.16 μL, 730.7 μmol) to a solution of (1S,2S,5R,6S)-2-(tert-butoxycarbonylamino)spiro[bicyclo[3.1.0]hexane-4,1′-cyclopropane]-2,6-dicarboxylic acid (0.09 g, 292.29 μmol) in N,N-dimethylformamide (2 mL). Stir at room temperature for 1.5 hours under nitrogen. Quench with water and extract with ethyl acetate. Separate the layers and filter the organics through a hydrophobic frit before concentrating to dryness to yield the crude product (134 mg). Purify by flash chromatography eluting with ethyl acetate:iso-hexane (1:99 to 25:75) to give a clear oil. Purify further by flash chromatography eluting with ethyl acetate:iso-hexane (1:99 10:90) to yield the title product (105 mg, 68%) as a clear oil. MS (m/z): 514 (M+23).
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[CH2:4][CH2:3][NH:2]1.[CH:13](=O)[CH3:14].C(O)(=O)C.C([BH3-])#N.[Na+]>CO.C(Cl)Cl.O>[CH2:13]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][C:8]([C:11]#[N:12])=[CH:7][CH:6]=2)[CH2:1]1)[CH3:14]
Reactant: N#Cc1ccc2c(c1)CNCC2
Reactant: CC=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCN1CCc2ccc(C#N)cc2C1
Reaction time: 1 h

Procedure:
To a solution of 1,2,3,4-tetrahydroisoquinoline-7-carbonitrile (ABCR; 500 mg; 3.16 mmol) in MeOH (5 mL) at 0° C. was added acetaldehyde (0.51 mL, 8.91 mmol) and acetic acid (5 μL) and the resulting mixture was stirred for 1 hour. Sodium cyanoborohydride (218 mg; 3.47 mmol) was added and the mixture was stirred for 5 hours and diluted with DCM (100 mL) and water (20 mL). The aqueous layer was extracted with DCM (3×20 mL), the combined organics were dried (MgSO4) and the solvent was removed in vacuo. The residue was purified by flash chromatography on a Biotage 25+M column, eluting with petrol containing increasing amounts of EtOAc to give the title compound as a brown oil. 1H NMR: (CDCl3, 400 MHz) δ 7.39 (1H, d, J=8.0 Hz), 7.33 (1H, s), 7.19 (1H, d, J=8.0 Hz), 3.62 (2H, s), 2.99-2.90 (2H, m), 2.77-2.70 (2H, m), 2.66-2.54 (2H, m), 1.19 (3H, t, J=7.2 Hz).
Reaction SMILES: C(OC(=O)[NH:7][C@@H:8]([CH2:31][CH2:32][CH3:33])[C:9](=[O:30])[NH:10][C@@H:11]1[C@@H:18]2[C@@H:14]([CH2:15][N:16]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH2:17]2)[CH2:13][CH2:12]1)(C)(C)C.C(N1C[C@@H]2[C@@H](NC(=O)[C@@H](N(C)C(=O)OC(C)(C)C)CC(C)C)CC[C@@H]2C1)C1C=CC=CC=1>>[F:28][C:26]([F:27])([F:29])[C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:16]2[CH2:17][C@@H:18]3[C@@H:11]([NH:10][C:9](=[O:30])[C@H:8]([CH2:31][CH2:32][CH3:33])[NH2:7])[CH2:12][CH2:13][C@@H:14]3[CH2:15]2)=[CH:21][CH:22]=1
Reactant: CCC[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@H]1CC[C@@H]2CN(Cc3ccc(C(F)(F)F)cc3)C[C@@H]21
Agent: CC(C)C[C@@H](C(=O)N[C@H]1CC[C@@H]2CN(Cc3ccccc3)C[C@@H]21)N(C)C(=O)OC(C)(C)C
Product: CCC[C@H](N)C(=O)N[C@H]1CC[C@@H]2CN(Cc3ccc(C(F)(F)F)cc3)C[C@@H]21

Procedure:
The title compound was prepared by substituting tert-Butyl-45)-1-oxo-1-((3aR,4S,6aS)-2-(4-(trifluoromethyl)benzyl)octahydrocyclopenta[c]pyrrol-4-ylamino)pentan-2-yl)carbamate from Step B for tert-butyl(S)-1-((3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylamino)-4-methyl-1-oxopentan-2-yl(methyl)carbamate in the procedure described in Example 348: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.19-8.22 (m, 1H), 7.64-7.67 (m, 2H), 7.50-7.53 (m, 2H), 4.37-4.43 (m, 1H), 3.53-3.58 (m, 2H), 3.46 (d, J=13.7 Hz, 1H), 2.86 (dd, J=9.0, 2.6 Hz, 1H), 2.49-2.57 (m, 1H), 2.43-2.49 (m, 1H), 2.33-2.36 (m, 2H), 2.19-2.25 (m, 1H), 2.11-2.20 (m, 2H), 2.06-2.14 (m, 1H), 1.91-2.01 (m, 1H), 1.82-1.90 (m, 1H), 1.62-1.69 (m, 1H), 1.38-1.58 (m, 4H), 0.84 (t, J=7.3 Hz, 3H); MS (ESI+) m/z 384 (M+H)+.
Reaction SMILES: [CH:1]([C:4]#[CH:5])([CH3:3])[CH3:2].C([Li])CCC.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[C:19](=[O:24])[C:20]([F:23])([F:22])[F:21]>C1COCC1>[NH2:11][C:12]1[C:13]([C:19]([OH:24])([C:5]#[C:4][CH:1]([CH3:3])[CH3:2])[C:20]([F:23])([F:21])[F:22])=[CH:14][C:15]([F:18])=[CH:16][CH:17]=1
Reactant: Nc1ccc(F)cc1C(=O)C(F)(F)F
Reactant: C#CC(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)C#CC(O)(c1cc(F)ccc1N)C(F)(F)F
Temperature: 0 °C
Reaction time: 1.25 h

Procedure:
To an ice-cooled solution of 1.89 mL of isopropylacetylene in 35 mL of dry THF was added dropwise over 5 min, 10.0 mL of 1.6 M n-butyllithium. The reaction mixture was stirred at 0° for 30 min after which time 828 mg of 1-(2-amino-5-fluorophenyl)-2,2,2-trifluoroethanone was added. The reaction mixture was stirred at 0° for 1.25 h after which time it was quenched with saturated aqueous ammonium chloride and poured onto water. This mixture was extracted twice with ether and the combined extracts were washed with brine dried and evaporated. The residue was purified by column chromatography on silica gel (elution with ethyl acetate/hexanes) affording 220 mg of the title compound as a tan solid.
Reaction SMILES: C1(S(Cl)(=O)=O)C=CC=CC=1.[CH2:11]([CH:16]1[O:21][C:20]2[CH:22]=[CH:23][C:24]([C:26]([NH2:28])=O)=[CH:25][C:19]=2[CH2:18][O:17]1)[CH2:12][CH2:13][CH2:14][CH3:15]>N1C=CC=CC=1>[CH2:11]([CH:16]1[O:21][C:20]2[CH:22]=[CH:23][C:24]([C:26]#[N:28])=[CH:25][C:19]=2[CH2:18][O:17]1)[CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCC1OCc2cc(C(N)=O)ccc2O1
Agent: O=S(=O)(Cl)c1ccccc1
Solvent: c1ccncc1
Product: CCCCCC1OCc2cc(C#N)ccc2O1
Reaction time: 8 h

Procedure:
1.85 ml of benzenesulphonyl chloride are added dropwise while stirring to a suspension of 1.2 g of 2-pentyl-1,3-benzodioxan-6-carboxamide in 10 ml of pyridine. The mixture is left to stand overnight and then the solution is extracted with 15 ml of 1N sodium hydroxide and ether. The aqueous phase is separated and back-extracted with ether. The combined organic phase is washed with 1N sodium hydroxide and then with water, dried over sodium sulphate, filtered and concentrated. The residue is treated with hot hexane. The mixture is decanted off from insoluble material and the solution is evaporated. The crude product is recrystallized once from hexane and twice from isopropanol. There is obtained 2-pentyl-1,3-benzodioxan-6-carbonitrile; m.p. 40.5°-41° C. (not liquid crystalline).
Reaction SMILES: COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[N+:23]([C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH2:32])=O)=[CH:28][CH:27]=1)([O-:25])=[O:24].O>O1CCOCC1>[N+:23]([C:26]1[CH:34]=[CH:33][C:29]([C:30](=[S:10])[NH2:32])=[CH:28][CH:27]=1)([O-:25])=[O:24]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: NC(=O)c1ccc([N+](=O)[O-])cc1
Solvent: O
Solvent: C1COCCO1
Product: NC(=S)c1ccc([N+](=O)[O-])cc1
Yield: 119.3 %

Procedure:
6.06 g (15 mmol) of Lawesson reagent is added to a solution of 4.15 g (25 mmol) of 4-nitrobenzamide in 100 ml of 1,4-dioxan. The reaction mixture is heated under reflux for two hours. After the solution has returned to ambient temperature, it is poured into 150 ml of water and extracted with 5 times 100 ml of ethyl acetate. The organic solution is dried over magnesium sulphate, filtered and concentrated under vacuum in order to produce a yellow oil which is purified on a silica gel column (eluant: heptane/ethyl acetate 1/1). The pure fractions are collected and concentrated under vacuum. 3.26 g of a yellow powder is obtained with a yield of 72%. Melting point: 165-167° C.
Reaction SMILES: Cl.[Cl:2][C:3]1[N:4]=[C:5]([C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][NH:16][CH2:15][C@H:14]2[O:19][CH3:20])=[O:11])[NH:6][C:7]=1[CH2:8][CH3:9].[Cl:21][C:22]1[CH:27]=[C:26]([C:28]([O:30][CH2:31]C)=[O:29])[CH:25]=[C:24](Cl)[N:23]=1.C(N(C(C)C)CC)(C)C>>[Cl:21][C:22]1[CH:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[C:24]([N:16]2[CH2:17][CH2:18][C@H:13]([NH:12][C:10]([C:5]3[NH:6][C:7]([CH2:8][CH3:9])=[C:3]([Cl:2])[N:4]=3)=[O:11])[C@H:14]([O:19][CH3:20])[CH2:15]2)[N:23]=1
Reactant: CCc1[nH]c(C(=O)N[C@H]2CCNC[C@H]2OC)nc1Cl
Reactant: CCOC(=O)c1cc(Cl)nc(Cl)c1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Product: CCc1[nH]c(C(=O)N[C@H]2CCN(c3cc(C(=O)OC)cc(Cl)n3)C[C@H]2OC)nc1Cl

Procedure:
The same operation as in Example (158a) was performed using cis(±)-4-chloro-5-ethyl-N-(3-methoxypiperidin-4-yl)-1H-imidazole-2-carboxamide hydrochloride obtained in Example (159a) (107 mg, 0.33 mmol), ethyl 2,6-dichloro-pyridine-4-carboxylate (65 mg, 0.32 mmol) and diisopropylethylamine (122 mg, 0.95 mmol), to obtain the title compound as a yellow brown oily substance.
Reaction SMILES: [CH3:1][C:2]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]2[C:3]=1[CH2:4][C:5]1[NH:6][C:7]3[C:12]([C:13]=12)=[CH:11][CH:10]=[CH:9][CH:8]=3.[BH3-]C#N.[Na+].[OH-].[Na+]>C(O)(=O)C.O>[CH3:1][C:2]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]2[C:3]=1[CH2:4][C@@H:5]1[C@H:13]2[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6]1
Reactant: COc1cc(C)c2c(c1)-c1c([nH]c3ccccc13)C2
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(C)c2c(c1)[C@@H]1c3ccccc3N[C@@H]1C2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirred suspension of 0.74 g of (0.00296 mol) of 5,6-dihydro-7-methyl-9-methoxyindeno[2,1-b]indole in 25 ml of acetic acid was added 0.93 g (0.0148 mol) of NaCNBH3 in portions during 5 minutes. The mixture was stirred for 3 hours at room temperature, whereafter it was diluted with water and then stirred for another hour. The resulting mixture was alkalinized with NaOH-solution (10M) to pH9, and was then extracted twice with ether. The combined organic phases were washed twice with aqueous NaCl-solution and dried (Na2SO4). After evaporation the residue was purified by chromatography on silica using methylene chloride as eluant. This gave 0.61 g (24%) of the expected product. M.p. 104° C. 1H NMR (CDCl3): 2.2 (3H,s), 3.0-3.4 (2H,dd), 3.4-3.5 (1H,bs), 3.75 (3H,s), 4.65-4.80 (2H,m), 6.4-7.4 (6H,m)--thereof 6.45 (1H,dd), 6.75 (1H,dd).
Reaction SMILES: Br[C:2]1[C:3](=[O:19])[C:4]([CH3:18])([CH3:17])[O:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH3:16])(=[O:15])=[O:14])=[CH:9][CH:8]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])[CH3:27]>C1(C)C=CC=CC=1.C(O)C.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>[C:26]([C:29]1[CH:34]=[C:33]([C:2]2[C:3](=[O:19])[C:4]([CH3:18])([CH3:17])[O:5][C:6]=2[C:7]2[CH:12]=[CH:11][C:10]([S:13]([CH3:16])(=[O:15])=[O:14])=[CH:9][CH:8]=2)[CH:32]=[CH:31][CH:30]=1)(=[O:28])[CH3:27]
Reactant: CC(=O)c1cccc(B(O)O)c1
Reactant: CC1(C)OC(c2ccc(S(C)(=O)=O)cc2)=C(Br)C1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CC(=O)c1cccc(C2=C(c3ccc(S(C)(=O)=O)cc3)OC(C)(C)C2=O)c1
Temperature: 90 °C
Reaction time: 12 h
Yield: 52.8 %

Procedure:
To a stirred solution of 4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (170 mg) in 30 ml toluene and 10 ml ethanol, were added 25 mg of tetrakis(triphenylphosphine)palladium(0), 10 ml of saturated aqueous sodium carbonate, and 130 mg of 3-acetylbenzeneboronic acid. The reaction solution was stirred at 90° C. for 12 hours. Then the solvent was removed under reduced pressure. The resulting residue was extracted with water and dichloromethane. The organic layer was concentrated in vacuo and the resulting residue was separated by column chromatography (hexane/ethylacetate=2:1) to afford 100 mg of 4-(3-acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone as a solid. mp: 189-190° C. NMR: δ1.60 (s, 6H), 2.59 (s, 3H), 3.07 (s, 3H), 7.48 (m, 2H), 7.82 (d, J=8.7 Hz, 2H), 7.90 (m, 2H), 7.94 (d, J=8.4 Hz, 2H). IR (cm−1): 1690, 1620, 1589, 1149, 958, 770.
Reaction SMILES: [Li].CCC(=O)CC(=O)CC.C([O:18][C:19]1[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH2:27][CH2:28][CH:29]=[CH:30][CH2:31][CH2:32][CH:33]([C:38](=[O:41])[CH2:39][CH3:40])[C:34](=[O:37])[CH2:35][CH3:36])=[CH:21][C:20]=1[O:42][CH3:43])C1C=CC=CC=1>>[OH:18][C:19]1[C:20]([O:42][CH3:43])=[CH:21][C:22]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH:33]([C:38](=[O:41])[CH2:39][CH3:40])[C:34](=[O:37])[CH2:35][CH3:36])=[CH:23][C:24]=1[O:25][CH3:26]
Reactant: CCC(=O)C(CCC=CCCc1cc(OC)c(OCc2ccccc2)c(OC)c1)C(=O)CC
Agent: CCC(=O)CC(=O)CC
Agent: [Li]
Product: CCC(=O)C(CCCCCCc1cc(OC)c(O)c(OC)c1)C(=O)CC

Procedure:
[I; Ar is 3,5-(CH3O)2 -4-HOC6H2, R0 is H, R' and R" are CH3CH2CO, Y is CH2CH2CH2CH2 ], yellow oil, was prepared from the compound of Preparation D22 and the lithium salt of 3,5-heptanedione, followed by catalytic hydrogenation of the resulting 4-[6-(4-benzyloxy-3,5-dimethoxyphenyl)-3-hexenyl]-3,5-heptanedione (light yellow oil).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4](S(C)(=O)=O)[C:5]2[N:10]=[C:9]([CH:11]3[CH2:13][CH2:12]3)[S:8][C:6]=2[N:7]=1.[C:18]([O-])([O-])=[O:19].[K+].[K+]>O1CCOCC1.CO>[NH2:1][C:2]1[N:3]=[C:4]([O:19][CH3:18])[C:5]2[N:10]=[C:9]([CH:11]3[CH2:13][CH2:12]3)[S:8][C:6]=2[N:7]=1
Reactant: O=C([O-])[O-]
Reactant: CS(=O)(=O)c1nc(N)nc2sc(C3CC3)nc12
Agent: [K+]
Solvent: C1COCCO1
Solvent: CO
Product: COc1nc(N)nc2sc(C3CC3)nc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 90 %

Procedure:
A mixture of 5-amino-2-cyclopropyl-7-(methylsulfonyl)thiazolo[5,4-d]pyrimidine (54 mg, 0.2 mmol) and K2CO3 (69 mg, 0.5 mmol) in dioxane (10 ml) and methanol (5 ml) was stirred at room temperature overnight. The reaction mixture was evaporated in vacuo and purified by flash chromatography on silica, the mobile phase being a mixture of methanol and dichloromethane (in a ratio of 1/60), yielding the pure title compound (40 mg, 90%).
Reaction SMILES: [CH3:1][CH:2]([OH:6])[CH2:3][CH2:4][CH3:5].[C:7]([O-])(=[O:9])[CH3:8].[Na+]>C(OC(=O)C)(=O)C>[C:7]([O:6][CH:2]([CH3:1])[CH2:3][CH2:4][CH3:5])(=[O:9])[CH3:8]
Reactant: CC(=O)[O-]
Reactant: CCCC(C)O
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: CCCC(C)OC(C)=O
Yield: 77 %

Procedure:
2-Pentanol (176 g, 2.0 mol, Aldrich) and sodium acetate (18 g, 10 Aldrich) were heated to 90° C. and then acetic anhydride (240 ml, BDH GPR) was added over a 1 hour period at 100-110° C. The mixture was heated to reflux for 4 hours. The reaction mixture was then cooled, washed with water, washed with aqueous sodium bicarbonate to neutrality, dried over sodium sulfate, and then concentrated. Fractional distillation of the crude residue under vacuum provided 1-methylbutyl acetate (80-81°/140-145 mm Hg, 77% yield), the structure of which was confirmed by mass spectroscopy, nuclear magnetic resonance spectroscopy, and infra red spectroscopy (not shown).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][CH3:12])(=[O:10])=[O:9])=[C:4]([C:13]([F:16])([F:15])[F:14])[CH:3]=1.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[OH:25]>>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([NH2:17])=[C:19]([O:25][C:2]2[CH:7]=[CH:6][C:5]([S:8]([CH2:11][CH3:12])(=[O:10])=[O:9])=[C:4]([C:13]([F:16])([F:15])[F:14])[CH:3]=2)[CH:20]=1
Reactant: Nc1ccc(Cl)cc1O
Reactant: CCS(=O)(=O)c1ccc(Br)cc1C(F)(F)F
Product: CCS(=O)(=O)c1ccc(Oc2cc(Cl)ccc2N)cc1C(F)(F)F

Procedure:
The subtitle compound was prepared by the example 3 step viii) using the product from example 22 step i) and 2-amino-5-chlorophenol. Yield 11.0 g
Reaction SMILES: [K].C([O-])(C)(C)C.[O:7]([C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:21]([N:23]([CH2:30][CH3:31])[C:24](=[O:29])[CH:25](Cl)[CH2:26][CH3:27])[CH3:22].C(OCC)C>CS(C)=O>[CH2:21]([N:23]([CH2:30][CH3:31])[C:24](=[O:29])[CH2:25][CH2:26][CH2:27][O:20][C:17]1[CH:16]=[CH:15][C:14]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:19][CH:18]=1)[CH3:22]
Reactant: Oc1ccc(Oc2ccccc2)cc1
Reactant: CCC(Cl)C(=O)N(CC)CC
Agent: CC(C)(C)[O-]
Agent: [K]
Solvent: CS(C)=O
Solvent: CCOCC
Product: CCN(CC)C(=O)CCCOc1ccc(Oc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
17 g of potassium-tert.-butanolate is added at 10° C to a solution of 28 g of 4-phenoxy-phenol in 100 ml of anhydrous dimethylsulphoxide. After the base has completely dissolved, an addition is made dropwise in the course of 2 hours, with stirring, of 26.5 g of chlorobutyric acid diethylamide dissolved in 20 ml of dimethylsulphoxide and the whole is further stirred overnight at room temperature. For further processing, the reaction mixture is poured into ice water, and extraction is repeatedly performed with diethyl ether. The combined ether phases are washed four times with cold 10% potassium hydroxide solution and subsequently repeatedly with water; they are then dried by means of sodium sulphate. After the ether has been distilled off, there is obtained crude 4-[(4-phenoxy)-phenoxy]-butyric acid diethylamide, which is purified by chromatography on silica gel (eluant: ether/hexane 1:3), and recrystallised from isopropanol/hexane, M.P. 73°-74° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[N:10]=[N:11][N:12]([C:14]3[CH:15]=[C:16]([CH:20]=[CH:21][C:22]=3[CH3:23])[C:17](O)=[O:18])[CH:13]=2)[CH:6]=[N:7][CH:8]=1.[NH2:24][C:25]1[C:26]([O:40][CH3:41])=[C:27]([NH:35][S:36]([CH3:39])(=[O:38])=[O:37])[CH:28]=[C:29]([C:31]2([CH3:34])[CH2:33][CH2:32]2)[CH:30]=1>>[CH3:39][S:36]([NH:35][C:27]1[C:26]([O:40][CH3:41])=[C:25]([NH:24][C:17](=[O:18])[C:16]2[CH:20]=[CH:21][C:22]([CH3:23])=[C:14]([N:12]3[CH:13]=[C:9]([C:5]4[CH:6]=[N:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=4)[N:10]=[N:11]3)[CH:15]=2)[CH:30]=[C:29]([C:31]2([CH3:34])[CH2:32][CH2:33]2)[CH:28]=1)(=[O:38])=[O:37]
Reactant: COc1cncc(-c2cn(-c3cc(C(=O)O)ccc3C)nn2)c1
Reactant: COc1c(N)cc(C2(C)CC2)cc1NS(C)(=O)=O
Product: COc1cncc(-c2cn(-c3cc(C(=O)Nc4cc(C5(C)CC5)cc(NS(C)(=O)=O)c4OC)ccc3C)nn2)c1

Procedure:
Example 12 was prepared by coupling 3-[4-(5-methoxy-pyridin-3-yl)-[1,2,3]triazol-1-yl]-4-methyl-benzoic acid with N-[3-amino-2-methoxy-5-(1-methyl-cyclopropyl)-phenyl]-methanesulfonamide (U.S. Ser. No. 04/102,492) in the same manner as Example 1. LST MS m/z 563 [C28H30N6O5S+H]+.