Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[CH3:11][C@H:12]1[CH2:17][O:16][CH2:15][CH2:14][N:13]1[C:18]1[CH:23]=[C:22]([C:24]([S:27]([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)(=[O:29])=[O:28])([CH3:26])[CH3:25])[N:21]=[C:20]([C:36]2[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=2)[N:19]=1.C(=O)(O)[O-].[Na+].O>O1CCOCC1>[CH3:11][C@H:12]1[CH2:17][O:16][CH2:15][CH2:14][N:13]1[C:18]1[CH:23]=[C:22]([C:24]([S:27]([C:30]2[CH:31]=[CH:32][N:33]=[CH:34][CH:35]=2)(=[O:28])=[O:29])([CH3:26])[CH3:25])[N:21]=[C:20]([C:36]2[CH:37]=[CH:38][C:39]([NH:40][C:2](=[O:3])[O:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)=[CH:41][CH:42]=2)[N:19]=1
Reactant: C[C@H]1COCCN1c1cc(C(C)(C)S(=O)(=O)c2ccncc2)nc(-c2ccc(N)cc2)n1
Reactant: O=C(Cl)Oc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: C[C@H]1COCCN1c1cc(C(C)(C)S(=O)(=O)c2ccncc2)nc(-c2ccc(NC(=O)Oc3ccccc3)cc2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.7 %

Procedure:
Phenyl chloroformate (0.177 mL, 1.41 mmol) was added to 4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-4-ylsulfonylpropan-2-yl)pyrimidin-2-yl]aniline (0.640 g, 1.41 mmol) and sodium bicarbonate (0.178 g, 2.12 mmol) in dioxane (175 mL) at RT under air. The resulting slurry was stirred at RT for 2 hours. Two more portions of phenyl chloroformate (2×0.005 mL) were added and the reaction allowed to stir at RT. Water was then added to the reaction and the solids were filtered and dried in a vacuum oven at 55° C. overnight to give the desired material as a tan solid (0.758 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:10](=[O:11])[C:9](=[O:12])[NH:8][C:5]2=[N:6][CH:7]=1.Br[C:14]1[CH:15]=[C:16]([CH3:22])[CH:17]=[CH:18][C:19]=1[O:20][CH3:21]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([OH:11])([C:14]3[CH:15]=[C:16]([CH3:22])[CH:17]=[CH:18][C:19]=3[O:20][CH3:21])[C:9](=[O:12])[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: O=C1Nc2ncc(Br)cc2C1=O
Reactant: COc1ccc(C)cc1Br
Product: COc1ccc(C)cc1C1(O)C(=O)Nc2ncc(Br)cc21
Yield: 58.5 %

Procedure:
With 2.00 g of the compound obtained in Step 120-3 and 2.26 g of 3-bromo-4-methoxy toluene as starting materials, 1.80 g of the title compound was obtained by a similar method to Step 21-1.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:3][NH:4][CH2:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[NH:17]1[C:21](=[O:22])[CH2:20][CH2:19][C@H:18]1[C:23](O)=[O:24].O.OC1C2N=NNC=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[CH3:15][CH:14]([CH3:16])[CH2:13][CH:2]([NH:1][C:23]([CH:18]1[CH2:19][CH2:20][C:21](=[O:22])[NH:17]1)=[O:24])[CH2:3][NH:4][CH2:5][C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7]
Reactant: O=C1CC[C@@H](C(=O)O)N1
Reactant: CC(C)C[C@H](N)CNCC(=O)OC(C)(C)C
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Oc1cccc2[nH]nnc12
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)CC(CNCC(=O)OC(C)(C)C)NC(=O)C1CCC(=O)N1
Reaction time: 0.5 h

Procedure:
A solution of 1.54 g of (S)-N-(2-amino-4-methylpentyl)glycine, 1,1-dimethylethyl ester, 890 mg of L-pyroglutamic acid, and 904 mg of hydroxybenzotriazole, hydrate in 30 ml of N,N-dimethylformamide is cooled in ice and treated dropwise with a solution of 1.4 g of N,N'-dicyclohexylcarbodiimide in 5 ml of N,N-dimethylformamide. After stirring at 0° for 0.5 hours, the mixture is kept at room temperature overnight. The mixture is filtered and the solvent distilled off under high vacuum. The residue is taken up in ethyl acetate and the ethyl acetate washed two times with water. The water is adjusted to pH 6 and lyophilized. The residue is chromatographed on 95 g of silica gel eluting with chloroform/methanol, (94:6). Combining the appropriate fractions gives 1.2 g of [S-(R*,R*)]-N-[4-methyl-2-[[(5-oxo-2-pyrrolidinyl]carbonyl)amino]pentyl]glycine, 1,1-dimethylethyl ester. The product is homogeneous by thin layer chromatography.
Reaction SMILES: [NH2:1][S:2]([C:5]1[C:6]([Cl:25])=[CH:7][C:8]([NH:18][CH2:19][C:20]2[O:21][CH:22]=[CH:23][CH:24]=2)=[C:9]([CH:17]=1)[C:10]([O:12][CH2:13][CH2:14][CH2:15][OH:16])=[O:11])(=[O:4])=[O:3].[C:26]1(=[O:32])[O:31][C:29](=[O:30])[CH2:28][CH2:27]1.C1CN2C(=NCCC2)C1.C(#N)C>ClCCl>[NH2:1][S:2]([C:5]1[C:6]([Cl:25])=[CH:7][C:8]([NH:18][CH2:19][C:20]2[O:21][CH:22]=[CH:23][CH:24]=2)=[C:9]([CH:17]=1)[C:10]([O:12][CH2:13][CH2:14][CH2:15][O:16][C:26](=[O:32])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:11])(=[O:3])=[O:4]
Reactant: NS(=O)(=O)c1cc(C(=O)OCCCO)c(NCc2ccco2)cc1Cl
Reactant: O=C1CCC(=O)O1
Agent: C1CN=C2CCCN2C1
Solvent: ClCCl
Solvent: CC#N
Product: NS(=O)(=O)c1cc(C(=O)OCCCOC(=O)CCC(=O)O)c(NCc2ccco2)cc1Cl
Temperature: 25 °C
Reaction time: 10 h

Procedure:
A mixture of 3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propanol (805) (0.060 mole), succinic anhydride (Aldrich) (0.060 mole), DBN (1,5-diazabicyclo[4.3.0]non-5-ene,(Aldrich) (0.060 mole) and dry acetonitrile (50 mL) is stirred at ambient temperature for 10 hours. The reaction mixture is diluted with dichloromethane (200 mL) and extracted with 0.1 N hydrochloric acid solution, washed with water, and then with a saturated sodium chloride solution. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo to give crude product, which may be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent. The fractions that contain pure product may be combined and spin evaporated in vacuo to give to give 4-(3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoic acid (810).
Reaction SMILES: CS[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[CH2:21][CH2:20][CH:19]([OH:22])[CH2:18][CH2:17]3)[CH:13]=[C:12]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:11]=2)=[CH:5][CH:4]=1.O[O:30][S:31]([O-:33])=O.[K+].[CH3:35]C(C)=O.O>>[CH3:35][S:31]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[CH2:21][CH2:20][CH:19]([OH:22])[CH2:18][CH2:17]3)[CH:13]=[C:12]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:11]=2)=[CH:7][CH:8]=1)(=[O:33])=[O:30]
Reactant: CSc1ccc(Nc2nc(-c3ccccc3)cc(N3CCC(O)CC3)n2)cc1
Reactant: O=S([O-])OO
Reactant: CC(C)=O
Agent: [K+]
Solvent: O
Product: CS(=O)(=O)c1ccc(Nc2nc(-c3ccccc3)cc(N3CCC(O)CC3)n2)cc1

Procedure:
1-[2-(4-Methylsulfanyl-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol was oxidized (0.26 g, 0.66 mmol) with oxone (1.55 g, 2.64 mmol) in acetone-water (3:1) at room temperature for 1 hour.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH3:9][C:10]1[CH:14]=[CH:13][N:12]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[C:11]=1[C:25]#[N:26].S(=O)(O)[O-].[Na+].O>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:14]1[C:10]([CH3:9])=[C:11]([C:25]#[N:26])[N:12]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[CH:13]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(S(=O)(=O)n2ccc(C)c2C#N)cc1
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(S(=O)(=O)n2cc(Br)c(C)c2C#N)cc1
Temperature: 25 °C
Reaction time: 29 h

Procedure:
N-Bromosuccinimide (12.0 g, 67.4 mmol) is added all at once to a suspension of 3-methyl-1-(4-methylbenzenesulphonyl)-1H-pyrrole-2-carbonitrile (14.45 g, 55.6 mmol) in N,N-dimethylformamide (60 mL) at ambient temperature. The mixture is stirred at ambient temperature for 29 hours and is then cooled in an ice bath. Saturated aqueous sodium bisulphite solution (90 mL), water (90 mL) and ethyl acetate (250 mL) are then added. The phases are separated, and then the aqueous phase is extracted with ethyl acetate (2×70 mL). The combined organic phases are washed with 5% aqueous potassium bicarbonate solution (90 mL), water (3×90 mL), and then brine (3×90 mL). The organic phase is dried over Na2SO4, filtered and concentrated in vacuo. The crude product is purified by chromatography over silica gel using toluene and heptane as eluants to obtain the expected compound in the form of a solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([N:18]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[C:19]3=[O:29])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:36][C:37]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[CH:39][N:38]=1>O1CCOCC1.O.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>[CH3:36][C:37]1[CH:42]=[C:41]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16]([N:18]4[CH2:22][CH2:21][N:20]([CH:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[C:19]4=[O:29])=[O:17])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:40]=[CH:39][N:38]=1
Reactant: O=C(Nc1ccc(Oc2ccnc(Cl)c2)cn1)N1CCN(C2CCOCC2)C1=O
Reactant: Cc1cc(B2OC(C)(C)C(C)(C)O2)ccn1
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: [K+]
Solvent: C1COCCO1
Solvent: O
Product: Cc1cc(-c2cc(Oc3ccc(NC(=O)N4CCN(C5CCOCC5)C4=O)nc3)ccn2)ccn1
Temperature: 95 °C
Yield: 19.7 %

Procedure:
A mixture of Example C1 (0.250 g, 0.598 mmol), K2CO3 (0.165 g, 1.197 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.157 g, 0.718 mmol) in dioxane (8 mL) and water (2 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.069 g, 0.060 mmol), sparged again with Ar and heated at 95° C. for 36 h. The mixture was cooled to RT, treated with satd. NaHCO3 and extracted with EtOAc (4×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (56 mg, 20%). 1H NMR (400 MHz, DMSO-d6): δ 10.98 (s, 1 H), 8.59 (d, J=5.6 Hz, 1 H), 8.52 (d, J=5.2 Hz, 1H), 8.27 (d, J=3.0 Hz, 1 H), 8.08 (d, J=9.1 Hz, 1 H), 7.89 (s, 1 H), 7.81-7.74 (m, 2 H), 7.70 (d, J=2.4 Hz, 1 H), 6.97 (dd, J=5.6, 2.4 Hz, 1 H), 3.93-3.78 (m, 5 H), 3.49-3.35 (m, 4 H), 2.52 (s, 3 H), 1.77-1.65 (m, 2 H), 1.62-1.56 (m, 2H); MS (ESI) m/z: 475.2 (M+H+).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:8]([N:11]2[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([NH:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)=[O:19])=[CH:12]2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][O:37][C:38]2[CH:43]=[CH:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][CH:39]=2)[CH2:31][CH2:30]1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[CH3:28][N:29]1[CH2:30][CH2:31][N:32]([CH2:35][CH2:36][O:37][C:38]2[CH:43]=[CH:42][C:41]([C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([S:8]([N:11]4[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([NH:20][O:21][CH:22]5[CH2:27][CH2:26][CH2:25][CH2:24][O:23]5)=[O:19])=[CH:12]4)(=[O:10])=[O:9])[CH:3]=3)=[CH:40][CH:39]=2)[CH2:33][CH2:34]1
Reactant: CN1CCN(CCOc2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: O=C(/C=C/c1ccn(S(=O)(=O)c2cccc(Br)c2)c1)NOC1CCCCO1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CN1CCN(CCOc2ccc(-c3cccc(S(=O)(=O)n4ccc(/C=C/C(=O)NOC5CCCCO5)c4)c3)cc2)CC1
Temperature: 100 °C

Procedure:
(E)-3-[1-(3-Bromo-benzenesulfonyl)-1H-pyrrol-3-yl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide (7.9 g) and 1-methyl-4-{2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-ethyl}-piperazine (9.0 g) are dissolved in DME (300 mL). Under an inert gas atmosphere there are added (Ph3P)3PdCl2 (2.4 g) and 2M Na2CO3-solution (50 mL) and the mixture is heated to 100° C. for 2 h. The mixture is filtered, evaporated and the residue is treated with ethyl acetate and 5% solution of NaHCO3. The organic phase is dried and evaporated and the crude product is purified by silica gel flash chromatography. 5.7 g of the Ube compound are obtained.
Reaction SMILES: [S:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH2:5][N:4]([C:12](=[O:14])[CH3:13])[CH2:3][CH2:2]1.ClC1C=C(C=CC=1)C(OO)=[O:20]>ClCCl>[O:20]=[S:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH2:5][N:4]([C:12](=[O:14])[CH3:13])[CH2:3][CH2:2]1
Reactant: CC(=O)N1CCSc2ccccc2C1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CC(=O)N1CCS(=O)c2ccccc2C1
Reaction time: 0.25 h
Yield: 77.4 %

Procedure:
To a cooled solution of 1-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)ethanone (70 g, 0.33 mol) in dichloromethane (700 mL) was added a solution of 3-chloroperoxybenzoic acid (67 g, 0.33 mol) in dichloromethane (800 mL) dropwise at 0° C. After the addition, the reaction was stirred at the same temperature for 15 minutes. The resulting reaction mixture was washed with a saturated aqueous solution of sodium carbonate (500 mL×2) and a saturated aqueous solution of sodium sulfite (500 mL×2). The combined aqueous layers were extracted with dichloromethane (200 mL×2), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (eluting with 1-2% methanol in dichloromethane) to afford 57 g of the desired product (yield was 77%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[C:15]([O:19][C:20](=[O:31])[NH:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)([CH3:18])([CH3:17])[CH3:16].C(N(CC)CC)C.N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:15]([O:19][C:20](=[O:31])[NH:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:11]([F:14])([F:13])[F:12])[CH:4]=2)=[CH:26][CH:25]=1)([CH3:18])([CH3:16])[CH3:17]
Reactant: OB(O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)NCCc1ccc(O)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)NCCc1ccc(Oc2ccc(Cl)c(C(F)(F)F)c2)cc1
Reaction time: 0.25 h
Yield: 24157.4 %

Procedure:
Entire reaction was performed under dry air using syringe septa technique. 4 Å molecular sievies were added to a stirred solution of 4-chloro-3-(trifluoromethyl)phenylboronic acid (5.00 g, 0.022 mmol) and [2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert butyl ester (2.64 g, 0.051 mol, 2 eq) in dry DCM (120 ml) at ambient temperature in a flame dried flask flushed with dry air. The reaction was stirred for 15 min. After that, copper (II) acetate (5.33 g, 0.010 mol, 1.3 eq), triethylamine (7.34 ml, 0.052 mol, 5 eq) and pyridine (4.25 ml, 0.052 mol, 5 eq) were added in succession and the reaction was stirred for 50 hours. The reaction mixture was sequential washed with 0.5 M HCl (4×250 ml), water (3×150 ml) and brine (1×150 ml). Organic layers were combined, dried over Na2SO4/MgSO4, filtered and evaporated. Crude product was purified on Biotage SP1 Snap Si 100; 40 ml/min in the gradient of EtOAc in Cyclohexan: 0-30% in 25 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product {2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (2.21 g, yield=24%, purity=82%). [M+H]+=416.84 [M+H-56]+=360.27 1H NMR (300 MHz; CDCl3) δ/ppm 1.50 (s, 9H), 2.85 (t, J=6.97 Hz, 2H), 3.38-3.48 (m, 2H), 4.63 (br. S., 1H), 7.01 (d, J=8.57 Hz, 2H), 7.11 (dd, J=8.77, J=2.79 Hz, 1H), 7.25 (d, J=8.57 Hz, 2H), 7.36 (d, J=2.79 Hz, 1H), 7.47 (d, J=8.77 Hz, 1H)
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([C:32](O)=[O:33])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:35]([O:42][CH2:43][CH2:44][NH:45][CH:46]([CH3:48])[CH3:47])([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36].[Si](OCCN(C(C)C)C(C1C(OCC2C=CC=CC=2)=C(O)N=C(CC2(C3C=C(Cl)C=CC=3Cl)CCCC2)N=1)=O)(C(C)(C)C)(C)C>>[Si:35]([O:42][CH2:43][CH2:44][N:45]([CH:46]([CH3:48])[CH3:47])[C:32]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:33])([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36]
Reactant: CC(C)NCCO[Si](C)(C)C(C)(C)C
Reactant: O=C(O)c1nc(CC2(c3ccc4ccccc4c3)CCCC2)nc(O)c1OCc1ccccc1
Agent: CC(C)N(CCO[Si](C)(C)C(C)(C)C)C(=O)c1nc(CC2(c3cc(Cl)ccc3Cl)CCCC2)nc(O)c1OCc1ccccc1
Product: CC(C)N(CCO[Si](C)(C)C(C)(C)C)C(=O)c1nc(CC2(c3ccc4ccccc4c3)CCCC2)nc(O)c1OCc1ccccc1
Yield: 24.5 %

Procedure:
5-Benzyloxy-6-hydroxy-2-(1-naphthalen-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (219) (300.0 mg, 24.5%) was synthesized as a colorless liquid from 5-benzyloxy-6-hydroxy-2-(1-naphthalen-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (218) (850.0 mg, 1.87 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (610.5 mg, 2.80 mmol) following the procedure described for 5-benzyloxy-2-[1-(2,5-dichlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (206).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=3)[C:15]([OH:17])=O)[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(N(CC)CC)C.[Cl-].[N:30]1([CH2:35][CH2:36][NH2:37])[CH2:34][CH2:33][CH2:32][CH2:31]1>COCCOC>[NH2:1][C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=3)[C:15]([NH:37][CH2:36][CH2:35][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[O:17])[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Nc1ncnc2ccc(-c3cc(F)cc(C(=O)O)c3)nc12
Reactant: NCCN1CCCC1
Agent: [Cl-]
Solvent: COCCOC
Solvent: CCN(CC)CC
Product: Nc1ncnc2ccc(-c3cc(F)cc(C(=O)NCCN4CCCC4)c3)nc12
Reaction time: 1 h

Procedure:
3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-benzoic acid 3 (110 mg, 0.39 mmol) in DME (2 mL) was treated with triethylamine (0.11 mL, 0.77 mmol) and cooled in ice bath with salt, methanolsulfonyl chloride (0.05 mL, 0.58 mmol) was added, and continue stirred for 1 hour in ice bath, then 2-pyrrolidin-1-ylethanamine (CAS 7154-73-6) (0.07 mL, 0.58 mmol) was added, the reaction was stirred overnight. The reaction mixture was purified with prep HPLC to give pure 3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-N-(2-(pyrrolidin-1-yl)ethyl)benzamide 13. LC/MS (ESI+): m/z 381 (M+H). 1H NMR (400 MHz, DMSO) δ 8.75 (t, J=5.6 Hz, 1H), 8.66-8.49 (m, 3H), 8.44 (s, 1H), 8.29 (s, 1H), 8.20 (t, J=4.4 Hz, 2H), 8.05 (s, 1H), 7.73 (d, J=9.4 Hz, 1H), 3.62-3.39 (m, 2H), 2.65 (t, J=7.0 Hz, 2H), 2.54 (s, 4H), 1.82-1.59 (m, 4H).
Reaction SMILES: [NH2:1][C@@H:2]([CH3:22])[C:3]([NH:5][C@@H:6]([CH3:21])[C:7]([NH:9][CH2:10][CH2:11][CH2:12][NH:13][C:14]1[S:15][C:16]([CH:19]=[O:20])=[CH:17][N:18]=1)=[O:8])=[O:4].[CH3:23][C@H:24]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:25](O)=[O:26].ON1C2N=CC=CC=2N=N1.CN1CCOCC1.C(Cl)CCl>C(Cl)Cl>[CH:19]([C:16]1[S:15][C:14]([NH:13][CH2:12][CH2:11][CH2:10][NH:9][C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][C:25](=[O:26])[C@@H:24]([NH:28][C:29](=[O:30])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH3:23])[CH3:22])[CH3:21])=[N:18][CH:17]=1)=[O:20]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: C[C@H](N)C(=O)N[C@@H](C)C(=O)NCCCNc1ncc(C=O)s1
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: CN1CCOCC1
Solvent: ClCCCl
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCCCNc1ncc(C=O)s1
Temperature: 25 °C
Reaction time: 18 h
Yield: 80.1 %

Procedure:
Following the procedure as described in Example 24, except using the material from Example 72 (255 mg, 0.539 mmol), N-alpha-t-BOC-L-Alanine (117 mg, 0.620 mmol), 1-hydroxy-7-azabenzotriazole (36.7 mg, 0.269 mmol), CH2Cl2 (10 mL), N-methylmorpholine (250 μlit, 2.27 mmol), EDC (124 mg, 0.647 mmol), and stirring at room temp for 18 h, 215.3 mg (80%) of the title compound is obtained as a white solid. The desired product crystallized out of the reaction, is collected by vacuum filtration and dried under high vacuum for several hours. LC/MS (Condition A): ret. T=2.70 min, (M+H)+ 499.26. 1H NMR (500 MHz, methanol-d4) δ ppm 9.61 (1 H, d, J=2.14 Hz), 7.96 (1 H, d, J=2.14 Hz), 4.16-4.38 (2 H, m), 3.92-4.07 (1 H, m), 3.43 (2 H, t, J=6.26 Hz), 1.88 (2 H, t, J=5.95 Hz), 1.26-1.51 (18 H, m).
Reaction SMILES: [NH2:1][C:2]1[O:3][CH:4]([CH:8]([CH3:10])[CH3:9])[C:5](=[O:7])[N:6]=1.[Cl:11][C:12]1[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=1[CH2:14]N>>[Cl:11][C:12]1[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=1[CH2:14][NH:1][C:2]1[O:3][CH:4]([CH:8]([CH3:10])[CH3:9])[C:5](=[O:7])[N:6]=1
Reactant: CC(C)C1OC(N)=NC1=O
Reactant: NCc1ccccc1Cl
Product: CC(C)C1OC(NCc2ccccc2Cl)=NC1=O

Procedure:
Synthesis was performed from 2-amino-5-isopropyl-1,3-oxazol-4(5H)-one and 2-Chlorobenzylamine according to Method G+H.
Reaction SMILES: [C:1]([C:5]1[C:6]([O:18][CH2:19][O:20][CH3:21])=[C:7](B(O)O)[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:22]([C:25]1[S:29][C:28]2[CH:30]=[CH:31][CH:32]=[C:33](I)[C:27]=2[CH:26]=1)(=[O:24])[CH3:23].C(O)C.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:22]([C:25]1[S:29][C:28]2[CH:30]=[CH:31][CH:32]=[C:33]([C:7]3[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]=3[O:18][CH2:19][O:20][CH3:21])[C:27]=2[CH:26]=1)(=[O:24])[CH3:23]
Reactant: CC(=O)c1cc2c(I)cccc2s1
Reactant: COCOc1c(B(O)O)cc(C(C)(C)C)cc1C(C)(C)C
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: Cc1ccccc1
Solvent: CCO
Product: COCOc1c(-c2cccc3sc(C(C)=O)cc23)cc(C(C)(C)C)cc1C(C)(C)C
Yield: 70 %

Procedure:
A mixture of 620 mg (2.1 mmol) 3,5-di-tert-butyl-2-methoxymethoxy phenylboronic acid, 377 mg (1.24 mmol) of 2-acetyl-4-iodo benzo[b]thiophene, 72 mg (0.105 mmol, 5%) Pd(PPh3)4 6 mL of ethanol, 1.25 mL of Na2CO3 in 8 mL of toluene was heated to reflux for 12 hours. After cooling and work-up, the crude product was purified over a short silica gel plug (eluent: ethyl acetate/hexane: 10/90) to give 368.6 mg (0.868 mmol, yield: 70%) of pure 2-acetyl-4-(2-methoxymethoxy-3,5-di-tert-butylphenyl)benzo[b]thiophene as a clear oil. 1H-NMR (CDCl3), δ: 7.84 (d, J=7.9 Hz, 1H), 7.79 (s, 1H), 7.53 (t, J=7.4 Hz, 1H), 7.46 (d, J=2.6 Hz, 1H), 7.44 (d, J=2.6 Hz, 1H), 7.19 (d, J=2.5 Hz, 1H), 4.47 (d, J=4.5 Hz, 1H), 4.06 (dd, J=14.2, 7.0 Hz, 2H), 2.81 (s, 3H), 2.54 (s, 3H), 2.02 (s, 3H), 1.49 (s, 9H), 1.33 (s, 9H), 1.23 (t, J=7.3 Hz, 3H).
Reaction SMILES: [C:1]1([CH:7](O)[CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C1(C)C=CC=CC=1>[CH3:9][CH:8]=[CH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCC(O)c1ccccc1
Reactant: [H][H]
Solvent: Cc1ccccc1
Product: CC=Cc1ccccc1
Yield: 90 %

Procedure:
Compounds of Formula 1 readily catalyse the dehydration of olefins. Standard conditions were used to conduct these reactions. For example heating cyclohexanol in the presence of compounds of Formula 1 where R and R1 are hydrogen or R is hydrogen and R1 is a C1-40 alkyl, C2-40 alkenyl, C2-40 alkynyl, aryl or C1-8 alkylaryl fragment gave the desired cyclohexene. In a similar fashion treatment of 1-phenyl-1-propanol in toluene with catalysts of Formula 1 where R and R1 are hydrogen or R is hydrogen and R1 is a C1-40 alkyl, C2-40 alkenyl, C2-40 alkynyl, aryl or C1-8 alkylaryl fragment in toluene at 75° C. gave β-methyl styrene in greater than 90% yield. An advantage of this procedure is that the catalyst can simply be filtered off and reused without any apparent reduction in activity.