Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:13]=[C:6]2[C:7]([O:9][C:10](=[O:12])[NH:11][C:5]2=[CH:4][CH:3]=1)=O.[CH2:14]([NH:21][CH2:22]C(O)=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CS(C)=O>O>[CH2:14]([N:21]1[C:7](=[O:9])[C:6]2[CH:13]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[NH:11][C:10](=[O:12])[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(O)CNCc1ccccc1
Reactant: O=c1[nH]c2ccc(Br)cc2c(=O)o1
Solvent: CS(C)=O
Solvent: O
Product: O=C1CN(Cc2ccccc2)C(=O)c2cc(Br)ccc2N1
Temperature: 200 °C
Yield: 98.2 %

Procedure:
A mixture of 5-bromoisatoic anhydride (1 g, 4.13 mmol), N-benzylglycine (0.628 g, 4.13 mmol) and DMSO (3 mL) was heated in the microwave at 200° C. for one hour. After cooling, the mixture was diluted with water and the precipitate was filtered off, washed with water and dried, giving 4-benzyl-7-bromo-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (1.4 g, 98%) as an off-white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH2:28][OH:29])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].CCN(CC)CC.[CH3:37][C:38]1[CH:43]=[CH:42][C:41]([S:44](Cl)(=[O:46])=[O:45])=[CH:40][CH:39]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:37][C:38]1[CH:43]=[CH:42][C:41]([S:44]([O:29][CH2:28][CH2:27][C:22]2[C:21]3[C:25](=[C:17]([C:14]4[N:13]=[C:12]([C:4]5[CH:5]=[CH:6][C:7]([O:8][CH:9]([CH3:10])[CH3:11])=[C:2]([Cl:1])[CH:3]=5)[O:16][N:15]=4)[CH:18]=[CH:19][CH:20]=3)[N:24]([CH3:26])[CH:23]=2)(=[O:46])=[O:45])=[CH:40][CH:39]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)Oc1ccc(-c2nc(-c3cccc4c(CCO)cn(C)c34)no2)cc1Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCCc2cn(C)c3c(-c4noc(-c5ccc(OC(C)C)c(Cl)c5)n4)cccc23)cc1
Temperature: 20 °C
Reaction time: 12 h
Yield: 242.5 %

Procedure:
To a stirred solution of 2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethanol (D126) (30 mg), Et3N (0.1 mL) and DMAP (10 mg) in DCM (5 mL) was added 4-methylbenzenesulfonyl chloride (42 mg) in DCM (5 mL). The reaction mixture was stirred at 20° C. for 12 h. The reaction mixture was quenched with water, partitioned between DCM (25 mL) and water (25 mL). The organic phase was washed with water, saturated aqueous sodium carbonate and brine, dried over sodium sulphate and evaporated to give the crude product 2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl 4-methylbenzenesulfonate (D127) (100 mg). MS (ES): C29H28ClN3O5S requires 565; found 566.2 (M+H+).
Reaction SMILES: [CH2:1]([C:8]1([O:14][C:15]([NH:17][C@@H:18]([CH2:23][CH2:24][CH2:25][CH3:26])[C:19](OC)=[O:20])=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+].[C:30]1([P:36](=[CH:49][C:50]#[N:51])([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.O>O1CCCC1.O.CN(C)C1C=CN=CC=1>[C:50]([C:49](=[P:36]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:19]([C@@H:18]([NH:17][C:15](=[O:16])[O:14][C:8]1([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[CH2:23][CH2:24][CH2:25][CH3:26])=[O:20])#[N:51]
Reactant: CCCC[C@H](NC(=O)OC1(Cc2ccccc2)CCCCC1)C(=O)OC
Reactant: N#CC=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCCC[C@H](NC(=O)OC1(Cc2ccccc2)CCCCC1)C(=O)C(C#N)=P(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 62.7 %

Procedure:
To 1.90 g (5.26 mmol) of methyl(2S)-2-({[(1-benzylcyclohexyl)oxy]carbonyl}amino)hexanoate in 18 mL of tetrahydrofuran:water (1:1) was added 308.8 mg (7.36 mmol) of lithium hydroxide monohydrate and the mixture was stirred at room temperature for 4 h. The solution was concentrated and extracted with diethyl ether. The aqueous layer was acidified with 1 N hydrochloric acid and extracted with diethyl ether. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in 15 mL of dichloromethane, then 19.0 mg (155.4 μmol) of 4-dimethylaminopyridine was added. To this solution was added 983.4 mg (3.26 mmol) of (triphenylphosphoranylidene)acetonitrile, followed by 658.8 mg (3.42 mmol) of 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide, and the mixture was stirred at room temperature for 16 h. Water was added to the solution and it was extracted with ethyl acetate. The organic layer was washed with 10% citric acid, followed by saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography eluting with an ethyl acetate:hexanes solution (1:1) to give 1.29 g (39%) of 1-benzylcyclohexyl(1S)-1-[cyano(triphenylphosphoranylidene)acetyl]pentylcarbamate. Rf=0.32 (1:1 ethyl acetate:hexanes); 1H NMR (300 MHz, DMSO-d6) δ 7.74-7.70 (m, 3H), 7.62-7.50 (m, 12H), 7.22-7.12 (m, 5H), 6.90 (d, J=8 Hz, 1H), 4.60-4.52 (m, 1H), 3.23 (ABq, JAB=13 Hz, ΔνAB=40 Hz, 2H), 2.19 (d, J=13 Hz, 1H), 1.95 (d, J=16 Hz, 1H), 1.86-1.68 (m, 1H), 1.60-1.10 (m, 13H), 0.90 (t, J=7 Hz, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[CH:18]=[N:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([NH:34][C@@H:35]1[CH2:40][CH2:39][CH2:38][CH2:37][C@@H:36]1[OH:41])(=[O:33])=[O:32]>>[NH2:23][C:20]1[N:21]=[CH:22][C:17]([C:3]2[CH:4]=[CH:5][C:6]([C:25]3[C:26]([S:31]([NH:34][C@@H:35]4[CH2:40][CH2:39][CH2:38][CH2:37][C@@H:36]4[OH:41])(=[O:32])=[O:33])=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:7][C:2]=2[F:1])=[CH:18][N:19]=1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)nc3)c(F)c2)OC1(C)C
Reactant: O=S(=O)(N[C@@H]1CCCC[C@@H]1O)c1ccccc1Br
Product: Nc1ncc(-c2ccc(-c3ccccc3S(=O)(=O)N[C@@H]3CCCC[C@@H]3O)cc2F)cn1

Procedure:
The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and racemic 2-bromo-N-((cis)-2-hydroxycyclohexyl)-benzene-sulfonamide. MS (ESI): mass calcd. for C22H23FN4O3S, 442.15; m/z found, 443.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.51 (d, J=1.3, 2H), 8.17 (dd, J=8.0, 1.4, 1H), 7.64-7.59 (m, 1H), 7.57-7.51 (m, 1H), 7.44-7.31 (m, 4H), 5.30 (s, 2H), 4.83 (d, J=7.7, 1H), 3.78 (s, 1H), 3.20-3.11 (m, 1H), 1.72-1.65 (m, 1H), 1.57-1.10 (m, 8H).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[NH:15][N:16]=[C:17]([OH:18])[C:10]=23)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[C:25]([O:31][C@@H:32]1[C@@H:37]([O:38][C:39](=[O:44])[C:40]([CH3:43])([CH3:42])[CH3:41])[C@H:36]([O:45][C:46](=[O:51])[C:47]([CH3:50])([CH3:49])[CH3:48])[C@@H:35]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[O:34][C@@H:33]1Br)(=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27].C(#N)C>O>[C:1]1([CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[NH:15][N:16]=[C:17]([O:18][C@@H:33]4[O:34][C@H:35]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[C@@H:36]([O:45][C:46](=[O:51])[C:47]([CH3:48])([CH3:49])[CH3:50])[C@H:37]([O:38][C:39](=[O:44])[C:40]([CH3:41])([CH3:42])[CH3:43])[C@H:32]4[O:31][C:25](=[O:30])[C:26]([CH3:29])([CH3:27])[CH3:28])[C:10]=23)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(C)C(=O)OC[C@H]1O[C@H](Br)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Reactant: Oc1n[nH]c2nccc(CCc3ccccc3)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Oc2n[nH]c3nccc(CCc4ccccc4)c23)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Temperature: 50 °C
Reaction time: 8 h
Yield: 12.1 %

Procedure:
A mixture of 4-(2-phenylethyl)-1H-pyrazolo[3,4-b]-pyridin-3-ol (0.59 g), potassium carbonate (0.68 g), 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide (1.71 g) and acetonitrile (10 mL) was stirred at 50° C. overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with water twice and brine, and dried over an hydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1-1/1) to give the title compound (0.22 g).
Reaction SMILES: C([O:3][C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([P:11]([CH2:16][P:17]([O:22][CH2:23][CH3:24])([O:19][CH2:20][CH3:21])=[O:18])([O:13][CH2:14][CH3:15])=[O:12])=[CH:7][CH:6]=1)C.[OH-].[Li+]>CO.O>[CH2:20]([O:19][P:17]([CH2:16][P:11]([O:13][CH2:14][CH3:15])([C:8]1[CH:7]=[CH:6][C:5]([C:4]([OH:25])=[O:3])=[CH:10][CH:9]=1)=[O:12])([O:22][CH2:23][CH3:24])=[O:18])[CH3:21]
Reactant: CCOC(=O)c1ccc(P(=O)(CP(=O)(OCC)OCC)OCC)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCOP(=O)(CP(=O)(OCC)c1ccc(C(=O)O)cc1)OCC
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 4-[(Diethoxyphosphorylmethyl)-ethoxyphosphinoyl]-benzoic acid ethyl ester (3c) (1 g, 2.55 mmol) in methanol (25 mL) was slowly added lithium hydroxide (monohydrate, 0.11 g, 2.55 mmol) in water (25 mL). The resulting reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated to remove methanol and diluted with brine, then extracted with EtOAc (3×100 mL) until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over Na2SO4 and concentrated on rotary evaporator. The desired product (3d) was purified by silica gel flash chromatography as a pale yellow oil (0.91 g). 1H NMR (300 MHz, DMSO-d6) δ (ppm)): 1.13 (m, 9H), 2.94 (t, J=18.2 Hz, 2H), 3.85 (m, 6H), 7.88 (m, 2H), 8.02 (m, 2H), 12.60 (bs, 1H), 31P NMR (121 MHz, DMSO-d6) δ, 37.59 and 24.59
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([SH:23])=[CH:19][CH:18]=1>CN(C)C1C=CN=CC=1.C(O)C>[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([S:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][CH:3]=2)=[CH:19][CH:18]=1
Reactant: Nc1ccc(S)cc1
Reactant: FC(F)(F)c1ccc2c(Cl)ccnc2c1
Agent: CN(C)c1ccncc1
Solvent: CCO
Product: Nc1ccc(Sc2ccnc3cc(C(F)(F)F)ccc23)cc1
Yield: 74.1 %

Procedure:
4-Chloro-7-trifluoromethylquinoline (0.043 moles, 10.0 g), 4-aminothiophenol (0.043 moles, 5.3 g) and 4-dimethylaminopyridine (0.04 moles, 4.9 g) were stirred in 250 ml ethanol for 3 days. The reaction mixture was filtered, concentrated, ethyl acetate added, washed with water and dried over sodium sulfate. The solution was concentrated and the product purified by HPLC over silica gel eluted with 25% ethyl acetate/hexane to yield 4-(4-aminophenylthio)-7-trifluoromethylquinoline 10.2 g, 74%. Mass Spec (FD) 320. Calculated for C16H11F3N2S: C, 59.99; H, 3.46; N, 8.74. Found: C, 60.08; H, 3.49; N, 8.77.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)[OH:11])=[CH:6][C:5]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(C(C)C)CC)(C)C.O([Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:12]2[CH:13]=[CH:14][N:15]=[CH:16][CH:17]=2)[O:11][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])=[CH:6][C:5]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: COC(=O)c1ccc(C(O)c2ccncc2)cc1-c1ccccc1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)c1ccc(C(O[Si](C)(C)C(C)(C)C)c2ccncc2)cc1-c1ccccc1
Reaction time: 18 h
Yield: 93 %

Procedure:
4-(4-Pyridylhydroxymethyl)-2-phenylbenzoic acid methyl ester (769 mg, 2.41 mmol), prepared as in Example 297A, diisopropylethylamine (0.84 mL, 4.8 mmol), and t-butyldimethylsilyl triflate (1.1 mL, 4.8 mmol) were dissolved in methylene chloride (50 mL) and stirred for 18 hours. TLC indicated the presence of the alcohol so additional base (1 mL) and triflate (0.5 mL) were added. After 15 minutes, all starting alcohol was consumed. The reaction mixture was washed with water, 5% NaHCO3, and brine, dried over Na2SO4, and concentrated. Chromatography on silica gel (20% ethyl acetate-hexane) provided the desired compound in a 93% yield.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8].[N:15]([C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[CH:21][N:22]=[CH:23]2)=[C:16]=[O:17]>C(OCC)C>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:10][CH2:11][N:12]([C:16]([NH:15][C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH:20]=[CH:21][N:22]=[CH:23]4)=[O:17])[CH2:13][CH2:14]2)[CH:5]=[CH:6][C:7]=1[CH3:8]
Reactant: Cc1ccc(N2CCNCC2)cc1C
Reactant: O=C=Nc1cccc2cnccc12
Solvent: CCOCC
Product: Cc1ccc(N2CCN(C(=O)Nc3cccc4cnccc34)CC2)cc1C

Procedure:
1-(3,4-Dimethylphenyl)piperazine (194 mg, 1.02 mmol) in diethyl ether (20 mL) was treated with an ethereal solution of 5-isocyanatoisoquinoline. The precipitate that formed was collected by filtration, washed with diethyl ether, and air-dried to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ 9.29 (d, 1H, J=0.7 Hz), 8.82 (s, 1H), 8.49 (d, J=6.2 Hz, 1H), 7.90-7.93 (m, 1H), 7.76-7.79 (m, 1H), 7.61-7.71 (m, 2H), 7.00 (d, 1H, 8.5 Hz), 6.83 (d, 1H, J=2.4 Hz), 6.73 (dd, 1H, J=8.3 Hz, 2.5 Hz), 3.67 (m, 4H), 3.15 (m, 4H), 2.19 (s, 3H), 2.13 (s, 3H); MS (ESI+) m/z 361 (M+H).
Reaction SMILES: [F:1][C:2]1([F:35])[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[CH:11][C:10]([C:13]3[O:17][N:16]=[C:15]([C:18]4[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:20][C:19]=4[CH3:33])[N:14]=3)=[CH:9][C:8]=2I)[CH2:3]1.[CH3:36][Si:37]([C:40]#[CH:41])([CH3:39])[CH3:38].C(NC(C)C)(C)C>O1CCOCC1.[Cu](I)I.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:1][C:2]1([F:35])[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[CH:11][C:10]([C:13]3[O:17][N:16]=[C:15]([C:18]4[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:20][C:19]=4[CH3:33])[N:14]=3)=[CH:9][C:8]=2[C:41]#[C:40][Si:37]([CH3:39])([CH3:38])[CH3:36])[CH2:3]1
Reactant: Cc1cc(CCC(=O)OC(C)(C)C)ccc1-c1noc(-c2cnc(N3CCC(F)(F)C3)c(I)c2)n1
Reactant: C#C[Si](C)(C)C
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: I[Cu]I
Solvent: C1COCCO1
Solvent: CC(C)NC(C)C
Product: Cc1cc(CCC(=O)OC(C)(C)C)ccc1-c1noc(-c2cnc(N3CCC(F)(F)C3)c(C#C[Si](C)(C)C)c2)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 75.9 %

Procedure:
To a solution of 61 mg (0.10 mmol) of tert-butyl 3-(4-(5-(6-(3,3-difluoropyrrolidin-1-yl)-5-iodopyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate (from EXAMPLE 34) in 5.0 mL of 1,4-dioxane were added 1 mg (0.005 mmol) of copper(II) iodide, 20 mg (0.21 mmol) of (trimethylsilyl)acetylene, 12 mg (0.12 mmol) of diisopropylamine, and 2.6 mg (0.005 mmol) of bis(tri-tert-butylphosphine)palladium(0). The mixture was stirred at rt for 16 h and concentrated. Chromatography on a Biotage 25S cartridges using 9:1 v/v hexanes/EtOAc as the eluant afforded 43 mg of a yellow solid as the title compound: 1HNMR (500 MHz, CDCl3) δ 0.26 (s, 9H), 1.45 (s, 9H), 2.46 (m, 2H), 2.58 (t, J=7.8, 2H), 2.66 (s, 3H), 2.96 (t, J=7.8, 2H), 4.15 (t, J=7.3, 2H), 4.32 (t, J=13, 2H), 7.18 (s, 1H), 7.19 (s, 1H), 8.01 (m, 1H), 8.34 (d, J=2.3, 1H), 8.88 (d, J=2.3, 1H).
Reaction SMILES: [CH:1]1([C:4]2[N:9]=[C:8](O)[CH:7]=[CH:6][N:5]=2)[CH2:3][CH2:2]1.P(Cl)(Cl)([Cl:13])=O>>[Cl:13][C:8]1[CH:7]=[CH:6][N:5]=[C:4]([CH:1]2[CH2:3][CH2:2]2)[N:9]=1
Reactant: Oc1ccnc(C2CC2)n1
Reactant: O=P(Cl)(Cl)Cl
Product: Clc1ccnc(C2CC2)n1
Reaction time: 3 h

Procedure:
2-Cyclopropylpyrimidin-4-ol (1.0 g, 7.34 mmol) was suspended in phosphorous oxychloride (5.0 mL, 53.6 mmol) and over the course of about one hour, the solid went into solution. After three hours, the solution was concentrated, diluted with ethyl acetate, washed with saturated sodium bicarbonate, water, saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated. The crude mixture was purified by silica gel chromatography to yield the title compound.
Reaction SMILES: CO[C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1.[NH2:26][CH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([C:13]2[C:12]([CH2:11][O:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([NH:26][CH:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[O:25])=[CH:5][N:6]=3)=[C:16]([CH3:17])[O:15][N:14]=2)=[CH:19][CH:20]=1
Reactant: NC1CCOCC1
Reactant: COC(=O)c1ccc(OCc2c(-c3ccc(Cl)cc3)noc2C)nc1
Product: Cc1onc(-c2ccc(Cl)cc2)c1COc1ccc(C(=O)NC2CCOCC2)cn1
Yield: 77 %

Procedure:
As described for example 117, 6-[3-(4-chloro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (108 mg, 0.3 mmol) was converted, using 4-aminotetrahydropyran instead of 2,2,2-trifluoroethylamine, to the title compound (99 mg, 77%) which was obtained as a white solid. MS: m/e=428.1 [M+H]+.
Reaction SMILES: [NH4+:1].C([O-])(=O)C.ClC(Cl)(Cl)[C:8]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:25])[C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[CH:13][C:12]=1[C:26](=O)[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=1)=[O:9].O>CS(C)=O>[Cl:33][C:29]1[CH:28]=[C:27]([C:26]2[C:12]3[C:11](=[CH:16][CH:15]=[C:14]([C:17](=[O:25])[C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[CH:13]=3)[NH:10][C:8](=[O:9])[N:1]=2)[CH:32]=[CH:31][CH:30]=1
Reactant: [NH4+]
Reactant: O=C(c1ccc(F)cc1)c1ccc(NC(=O)C(Cl)(Cl)Cl)c(C(=O)c2cccc(Cl)c2)c1
Agent: CC(=O)[O-]
Solvent: O
Solvent: CS(C)=O
Product: O=C(c1ccc(F)cc1)c1ccc2[nH]c(=O)nc(-c3cccc(Cl)c3)c2c1
Temperature: 60 °C
Reaction time: 4 h
Yield: 72.4 %

Procedure:
Acetic acid, ammonium salt (0.135 mol) was added at room temperature to a mixture of intermediate 4 (0.0675 mol) in DMSO (300 ml). The mixture was stirred at 60° C. for 4 hours, then brought to room temperature and poured out into water. The precipitate was filtered, washed with water, taken up in warm CH3CN, filtered, washed again with CH3CN, then with diethyl ether and dried under a vacuo, yielding 18.5 g (72%) of intermediate 5. The mother layer was purified by column chromatography over silica gel (15-40 μm) (eluent: DCM/MeOH:NH4OH 95/5/0.1). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from 2-propanone/diethyl ether. The precipitate was filtered off and dried, yielding 1.8 g (7%) of 4-(3-chlorophenyl)-6-(4-fluorobenzoyl)-2(1H)-quinazolinone (intermediate 5), mp. 226° C.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[O:16][C@H:7]([O:8]CC2C=CC=CC=2)[C@H:6]([NH:17][C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[C@@H:5]([OH:28])[C@@H:4]1[OH:29].[CH2:30]([OH:39])[C@H:31]1[O:36][C:34](=[O:35])[C@H:33]([OH:37])[C@@H:32]1[OH:38]>O1CCOCC1>[CH2:21]([C@@:7]1([O:16][C@H:3]([CH2:2][NH:1][C:34]([C@@H:33]([C@@H:32]([C@@H:31]([CH2:30][OH:39])[OH:36])[OH:38])[OH:37])=[O:35])[C@@H:4]([OH:29])[C@H:5]([OH:28])[C@H:6]1[NH:17][C:18]([O:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:19])[OH:8])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: NC[C@H]1O[C@H](OCc2ccccc2)[C@H](NC(=O)OCc2ccccc2)[C@@H](O)[C@@H]1O
Reactant: O=C1O[C@H](CO)[C@@H](O)[C@H]1O
Solvent: C1COCCO1
Product: O=C(N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CNC(=O)[C@H](O)[C@H](O)[C@H](O)CO)O[C@@]1(O)Cc1ccccc1)OCc1ccccc1

Procedure:
Benzyl 6-amino-2-benzyloxycarbonylamino-2,6-didesoxy-α-D-glucopyranoside (see Ex. 9.C.) and D-ribonic acid g-lactone were reacted as described in Ex. 14.A. and gave D-ribonic acid (benzyl 2-benzyloxycarbonylamino-2,6-didesoxy-α-D-gluco-pyranosid-6-yl)-amide, [α]+81.5° (c 0.2; dioxan), MS: m/z 551.4 ([M+H]+).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[C:26]([C:27](=[O:29])[NH2:28])=[C:25](Cl)[N:24]=[C:23]([S:31][CH3:32])[N:22]=3)=[CH:16][C:15]=2[CH3:33])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[NH2:35][NH2:36]>O1CCOCC1>[C:27]([C:26]1[C:21]([NH:20][C:17]2[CH:18]=[CH:19][C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]3)=[C:15]([CH3:33])[CH:16]=2)=[N:22][C:23]([S:31][CH3:32])=[N:24][C:25]=1[NH:35][NH2:36])(=[O:29])[NH2:28]
Reactant: CSc1nc(Cl)c(C(N)=O)c(Nc2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)c(C)c2)n1
Reactant: NN
Solvent: O
Solvent: C1COCCO1
Product: CSc1nc(NN)c(C(N)=O)c(Nc2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)c(C)c2)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a suspension of the product of Example 17C (246 mg, 0.5 mmol) in 1,4-dioxane (10 mL) was added 85% hydrazine hydrate (125 mg, 2.5 mmol) dropwise. The mixture was stirred at room temperature for 3 hours, extracted with ethyl acetate and the organic layer was washed with water, dried over sodium sulfate, filtered and concentrated. The residue was washed with petroleum ether to provide the title compound. MS: 489 (M+H+).
Reaction SMILES: Cl[C:2]1[C:3]2[S:13][C:12]3[N:14]=[C:15]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:16]=[C:17]([CH3:18])[C:11]=3[C:4]=2[N:5]=[C:6]([S:8][CH2:9][CH3:10])[N:7]=1.[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>O1CCCC1>[CH2:9]([S:8][C:6]1[N:7]=[C:2]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[C:3]2[S:13][C:12]3[N:14]=[C:15]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:16]=[C:17]([CH3:18])[C:11]=3[C:4]=2[N:5]=1)[CH3:10]
Reactant: C1CNCCN1
Reactant: CCSc1nc(Cl)c2sc3nc(-c4ccccc4)cc(C)c3c2n1
Solvent: C1CCOC1
Product: CCSc1nc(N2CCNCC2)c2sc3nc(-c4ccccc4)cc(C)c3c2n1

Procedure:
0.63 g (1.7 mmol) 4-chloro-2-ethylthio-9-methyl-7-phenyl-pyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidine is stirred with 0.29 g (3.4 mmol) piperazine in 10 ml tetrahydrofuran at room temperature for 1 h. The precipitate is sucked off, washed with some water and suck dried. Thereafter, the precipitate is suspended in about 300 ml dichloromethane, fully stirred, filtrated and the solvent of the filtrate is removed. 0.67 g (93%) of the title substance is obtained. ESI-MS [m/z]: 422, melting point: 150-154° C.
Reaction SMILES: [Br:1]Br.[CH2:3]([C:10]1[S:14][C:13]2[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=2[C:11]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=2)=[CH:21][CH:20]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([O-])(=O)C.[K+].O>C(O)(=O)C>[CH2:3]([C:10]1[S:14][C:13]2[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=2[C:11]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:26]=[CH:27][C:28]([OH:31])=[C:29]([Br:1])[CH:30]=2)=[CH:21][CH:20]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: BrBr
Reactant: Oc1ccc(-c2ccc(-c3c(Cc4ccccc4)sc4ccccc34)cc2)cc1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: Oc1ccc(-c2ccc(-c3c(Cc4ccccc4)sc4ccccc34)cc2)cc1Br
Yield: 26.6 %

Procedure:
Bromine (1.47 mL, 28.69 mmol) in acetic acid (50 mL) was added dropwise over a 30 minutes period into a cold (5° C.) mixture of 4′-(2-benzyl-benzo[b]thiophen-3-yl)-biphenyl-4-ol (7.5 g, 19.13 mmol), potassium acetate (18.6 g, 190.13 mmol), and acetic acid (200 mL). After the addition the mixture was poured into water, and extracted with ethyl ether. The organic extracts were washed with aqueous sodium bisulfite and dried over MgSO4. Evaporation and purification by flash chromatography on silica gel (hexanes/EtAOc/CH2Cl2 3:1:1) gave 4′-(2-benzyl-benzo[b]thiophen-3-yl)-3-bromo-biphenyl-4-ol as a light yellow solid (2.4 g): mp 54-56° C. MS m/e 477 (M+);