Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([Si:3]([CH2:8][CH3:9])([CH2:6][CH3:7])[C:4]#[CH:5])[CH3:2].C(N(CC)CC)C.Br[C:18]1[C:19]([NH2:25])=[N:20][CH:21]=[C:22]([Br:24])[N:23]=1>O1CCCC1.CCOC(C)=O.[NH4+].[OH-].[Cu]I.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>[Br:24][C:22]1[N:23]=[C:18]([C:5]#[C:4][Si:3]([CH2:8][CH3:9])([CH2:6][CH3:7])[CH2:1][CH3:2])[C:19]([NH2:25])=[N:20][CH:21]=1
Reactant: C#C[Si](CC)(CC)CC
Reactant: Nc1ncc(Br)nc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC[Si](C#Cc1nc(Br)cnc1N)(CC)CC
Temperature: 25 °C
Reaction time: 18 h
Yield: 91 %

Procedure:
Triethyl(ethynyl)silane (6.102 g, 7.793 mL, 43.49 mmol) followed by triethylamine (5.201 g, 7.164 mL, 51.40 mmol) was added to a thoroughly degassed suspension of 3,5-dibromopyrazin-2-amine (10 g, 39.54 mmol), copper(I) iodide (753.0 mg, 3.954 mmol) and Pd(PPh3)2Cl2 (2.775 g, 3.954 mmol) in tetrahydrofuran (200.0 mL) and the resulting solution stirred at ambient temperature over 18 hours. (On addition reaction mixture changes colour rapidly from yellow to orange to red to dark red and brown and then orange). Reaction mixture is cooled to ambient temperature and then diluted with EtOAc and 10% solution of NH4OH (100 mL) added and the layers separated. EtOAc layer washed once more with 10% NH4OH. Aqueous layer extracted further with EtOAc (×3) and combined organics dried over (MgSO4), filtered and concentrated in vacuo to a brown oil. Purified on Companion using a 330 g pre-packed silica column loading with DCM and eluting with 0-100% Petrol/DCM. Relevant fractions combined and concentrated in vacuo to give a brown oil (11.24 g, 91%). 1H NMR (400.0 MHz, DMSO) δ 0.67-0.74 (m, 6H), 0.99-1.03 (m, 9H), 6.72 (s, 2H) and 8.14 (s, 1H) ppm; MS (ES+) 314.06.
Reaction SMILES: Br[C:2]1[CH:24]=[CH:23][C:5]([CH2:6][N:7]2[CH:22]=[C:10]3[C:11](=[O:21])[N:12]([CH3:20])[C:13]4[N:14]([CH2:15][C:16]([CH3:19])([CH3:18])[N:17]=4)[C:9]3=[N:8]2)=[CH:4][CH:3]=1.[C:25]1([OH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1C(=O)CCC1.O.Cl[Cu]>[O:31]([C:2]1[CH:24]=[CH:23][C:5]([CH2:6][N:7]2[CH:22]=[C:10]3[C:11](=[O:21])[N:12]([CH3:20])[C:13]4[N:14]([CH2:15][C:16]([CH3:19])([CH3:18])[N:17]=4)[C:9]3=[N:8]2)=[CH:4][CH:3]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CN1C(=O)c2cn(Cc3ccc(Br)cc3)nc2N2CC(C)(C)N=C12
Reactant: Oc1ccccc1
Agent: Cl[Cu]
Agent: CC(C)(C)C(=O)CC(=O)C(C)(C)C
Agent: O=C([O-])[O-]
Solvent: CN1CCCC1=O
Solvent: O
Product: CN1C(=O)c2cn(Cc3ccc(Oc4ccccc4)cc3)nc2N2CC(C)(C)N=C12
Temperature: 120 °C
Yield: 84.4 %

Procedure:
2-(4-Bromobenzyl)-7,8-dihydro-5,7,7-trimethyl-[2H]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one (118 g, 304 mmol) is added into a suspension of phenol (57 g, 606 mmol) and cesium carbonate (200 g, 614 mmol) in NMP (900 mL), followed by 2,2,6,6-tetramethylheptane-3,5-dione (7 mL, 33.5 mmol) and CuCl (15 g, 152 mmol). The reaction mixture is heated at 120° C. under argon atmosphere for 10 h. After the completion of the reaction, the mixture is diluted with water (4 L), and then extracted with ethyl acetate. The combined organic phase is evaporated to dryness. The obtained crude product is purified by silica gel column chromatography to give 103 g of product (yield: 84%). MS (ESI) m/z 402.2 [M+H]+.
Reaction SMILES: CCOCC.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([S:22][C:23]2[S:24][CH:25]=[CH:26][CH:27]=2)=[C:17]([CH:21]=1)[C:18](O)=[O:19]>O>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([S:22][C:23]2[S:24][CH:25]=[CH:26][CH:27]=2)=[C:17]([CH:21]=1)[CH2:18][OH:19]
Reactant: O=C(O)c1cc(Cl)ccc1Sc1cccs1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: OCc1cc(Cl)ccc1Sc1cccs1

Procedure:
To 30 ml of abs. ether cooled to 3° is added under nitrogen 1.14 g (0.03 mole) of lithium aluminium hydride, and there is then added dropwise at 5°-10° with stirring, within half an hour, a solution of 5.4 g (0.02 mole) of 5-chloro-2-(2-thienylthio)-benzoic acid (produced according to Swiss Patent Specification No. 405,354; C.A. 66, P 2550e) in 45 ml of abs. ether. After completion of the dropwise addition, the mixture is refluxed for 16 hours; and there is thereupon slowly added dropwise at 3°-7° 5 ml of water. The occurring precipitate is filtered off with suction, and subsequently well washed with ether. The filtrate is concentrated in vacuo, and the residue is recrystallised from carbon tetrachloride to yield 5-chloro-2-(2-thienylthio)-benzyl alcohol having a melting point of 95°-96°.
Reaction SMILES: C1(N=C=O)C=CC=CC=1.[C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][CH:13]=1)#[CH:11].[N+:22]([CH2:25][CH3:26])([O-])=[O:23].C(N(CC)CC)C>C1C=CC=CC=1.O>[CH3:26][C:25]1[CH:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:16][CH:17]=2)[O:23][N:22]=1
Reactant: C#Cc1ccc(C(C)(C)C)cc1
Reactant: CC[N+](=O)[O-]
Solvent: O
Solvent: CCN(CC)CC
Solvent: O=C=Nc1ccccc1
Product: Cc1cc(-c2ccc(C(C)(C)C)cc2)on1

Procedure:
4.57 ml (42.12 mmol) of phenyl isocyanate are added dropwise at room temperature to a solution of 5 g (31.59 mmol) of 1-ethynyl-4-(tert-butyl)benzene, 0.75 ml (10.53 mmol) of nitroethane and 0.29 ml (2.10 mmol) of triethylamine in 100 ml of benzene. The reaction mixture is then stirred under reflux for 12 h. After cooling, the suspension is mixed with water (50 ml) and stirred at room temperature for a further 4 h. The precipitate is filtered off with suction and washed with benzene (10 ml). The organic phase of the filtrate is separated off, dried with magnesium sulfate and concentrated. The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 9:1). 989 mg (14% of theory) of the title compound are obtained as a colorless oil.
Reaction SMILES: C([C:9]1([O:18][CH2:17][C@:15]([C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([OH:16])[C@:13]([C:27](=[O:34])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([OH:14])[C@@:11]1([C:35](=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[OH:12])[OH:10])(=O)C1C=CC=CC=1.[BrH:43].C(O)(=O)C.ClCCl>O>[Br:43][C:9]1([O:18][CH2:17][C@:15]([C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([OH:16])[C@:13]([C:27](=[O:34])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([OH:14])[C@@:11]1([C:35](=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[OH:12])[OH:10]
Reactant: Br
Reactant: O=C(c1ccccc1)C1(O)OC[C@@](O)(C(=O)c2ccccc2)[C@@](O)(C(=O)c2ccccc2)[C@]1(O)C(=O)c1ccccc1
Solvent: O
Solvent: CC(=O)O
Solvent: ClCCl
Product: O=C(c1ccccc1)[C@]1(O)[C@](O)(C(=O)c2ccccc2)COC(O)(Br)[C@@]1(O)C(=O)c1ccccc1
Temperature: 10 °C
Reaction time: 6 h
Yield: 70 %

Procedure:
While the internal temperature of the reactor containing 2.946 kg (5.20 mol) of 1,2,3,4-tetrabenzoyl-L-arabinopyranose was maintained at 0-20° C., 4.21 kg of a 30-33% hydrogen bromide/acetic acid solution was added dropwise thereto, and the mixture was stirred at room temperature for 6 hours. After completion of the reaction, 1.296 liters of dichloromethane was added to the reaction solution, which was then stirred for 30 minutes. Next, the solution was added dropwise to a reactor containing 4.162 liters of purified water, and was stirred for 30 minutes, and then separated into layers. The water layer was back-extracted with 1.296 liters of dichloromethane. The oil layer was washed two times with 0.195 kg of aqueous saturated sodium chloride solution and one time with 0.248 kg of aqueous saturated sodium bicarbonate solution, and then dried with sodium sulfate, and the solvent was removed by concentration. To the concentrated residue, 1.30 liters of dichloromethane was added, the solution was stirred for 2-3 hours, and 6.50 liters of hexane was added thereto. The resulting solution was cooled to 0-5° C., stirred for 3-4 hours, and then filtered. The filtered solids were washed with 2.76 liters of hexane and dried in a vacuum, thus obtaining 1.912 kg (70% yield) of 1-bromo-2,3,4-tribenzoyl-L-arabinopyranose. 1H NMR (CDCl3): δ 8.20˜7.90 (dd, 4H), 7.90˜7.80 (d, 2H), 7.70˜7.20 (m, 9H), 6.93 (d, 1H), 5.97 (dd, 1H), 5.82 (m, 1H), 5.70 (dd, 1H), 4.50 (d, 1H), 4.25 (d, 1H).
Reaction SMILES: C([O:4][CH2:5][CH2:6][C:7]([O:10][C:11](=[O:24])[C:12]([O:14][C:15]([CH3:23])([CH2:17][CH2:18][O:19]C(=O)C)[CH3:16])=[O:13])([CH3:9])[CH3:8])(=O)C>C(Cl)Cl.C(NC(C)C)(C)C>[OH:4][CH2:5][CH2:6][C:7]([O:10][C:11](=[O:24])[C:12]([O:14][C:15]([CH3:23])([CH2:17][CH2:18][OH:19])[CH3:16])=[O:13])([CH3:8])[CH3:9]
Reactant: CC(=O)OCCC(C)(C)OC(=O)C(=O)OC(C)(C)CCOC(C)=O
Solvent: ClCCl
Solvent: CC(C)NC(C)C
Product: CC(C)(CCO)OC(=O)C(=O)OC(C)(C)CCO

Procedure:
The cleavable diol is made in the following manner. To a solution of compound (73) in methylene chloride, diisopropylamine is added and the solution is stirred until reaction is complete. A standard aqueous workup is done and the diol should remain in the organic phase. Evaporate the solvent and collect bis(4-hydroxy-2-methylbutan-2-yl)oxalate (74).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:11][CH:12]([OH:15])[CH2:13][NH2:14].C(N(CC)CC)C>C(O)C>[N+:8]([C:7]1[C:2]([NH:14][CH2:13][CH:12]([OH:15])[CH3:11])=[N:3][CH:4]=[CH:5][CH:6]=1)([O-:10])=[O:9]
Reactant: CC(O)CN
Reactant: O=[N+]([O-])c1cccnc1Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(O)CNc1ncccc1[N+](=O)[O-]
Yield: 95.8 %

Procedure:
A mixture of 2-chloro-3-nitropyridine (10.0 g, 0.063 mole), DL-1-amino-2-propanol (7.1 g, 0.095 mole), and triethylamine (8.75 ml, 0.063 mole) in absolute ethanol was heated at reflux for 11/2 hours. The reaction mixture was evaporated to dryness and the residue was partitioned between water and methylene chloride. The water layer was separated and extracted with methylene chloride (2×). The combined methylene chloride layers were extracted with water and dried over sodium sulfate. The filtrate was evaporated to a yellow oil. The oil was purified on a silica gel column (200 g) eluting first with methylene chloride, followed by 5%, 10%, 25% (500 ml each), and finally 50% ethyl acetate/methylene chloride. The appropriate fractions (TLC using ethyl acetate) were combined and evaporated to an oil. A sample of the oil was dried at 50°-60° C., then at 70° C. for 6 hours to give 11.9 g (96%) of a yellow oil.
Reaction SMILES: Br[CH2:2][CH2:3][OH:4].[CH2:5]([SH:17])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C1(C)C=CC=CC=1>[CH2:5]([S:17][CH2:2][CH2:3][OH:4])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCS
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCSCCO
Temperature: 22 °C
Reaction time: 10 h
Yield: 76.5 %

Procedure:
A mixture of 2-bromoethanol (6.08 g, 48.7 mmol), dodecanethiol (9.86 g, 48.7 mmol) and potassium carbonate (11 g) in dry N,N-dimethylformamide (100 ml) was stirred at 22° C. for 10 h. The reaction mixture was then diluted with toluene (400 ml) washed with water and dried (magnesium sulfate). The solvent was evaporated under reduced pressure and the residue was filtered through a silica gel pad (toluene -ethyl acetate 95:5) and distilled under vacuum to give 9.18 g (77%) of 2-(dodecylthio)ethanol as a clear oil which solidified on standing: b.p. 100-105° C./0,01 torr (bulb to bulb distillation, air bath temperature); m.p. 31-32° C.
Reaction SMILES: Cl[C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3.[CH2:17]([NH:24][CH:25]([CH3:27])[CH3:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC([O-])(C)C.[Na+]>O1CCOCC1.CS(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:17]([N:24]([CH:25]([CH3:27])[CH3:26])[C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=c1[nH]c2ncccc2c2cc(Cl)ccc12
Reactant: CC(C)NCc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: CS(C)=O
Solvent: C1COCCO1
Product: CC(C)N(Cc1ccccc1)c1ccc2c(=O)[nH]c3ncccc3c2c1
Temperature: 150 °C
Reaction time: 0.08 h
Yield: 7 %

Procedure:
6 (200 mg, 0.87 mmol), N-benzylpropan-2-amine (0.58 mL, 3.47 mmol), Pd(OAc)2 (8 mg, 0.03 mmol), X-Phos (33 mg, 0.07 mmol), and NaOtBu (250 mg, 2.6 mmol) were suspended in dioxane (3 mL), and stirred for 5 minutes at 150° C. via microwave. The reaction solution was diluted with DMSO and filtered. The crude product was purified directly via prep-LC-MS to provide 448 (21 mg, 7% yield) as a white powder. LC-MS (M+H=344, obsd.=344). 1H NMR (400 MHz, DMSO-D6) δ 11.45 (m, 1H), 8.53 (m, 1H), 8.38 (m, 1H), 8.00 (s, 1H), 7.49 (m, 1H), 7.32 (m, 5H), 7.18 (m, 1H), 7.00 (m, 1H), 4.66 (s, 2H), 1.25 (d, J=6.6, 6H), 0.84 (m, 1H).
Reaction SMILES: P([O-])([O-])([O-])=O.I[C:7]1[CH:8]=[C:9](/[CH:17]=[CH:18]\[C:19]2[CH:24]=[CH:23][C:22](OC)=[C:21](O)[CH:20]=2)[CH:10]=[C:11](OC)[C:12]=1OC>>[C:9]1(/[CH:17]=[CH:18]\[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:10]=[CH:11][CH:12]=[CH:7][CH:8]=1
Reactant: COc1ccc(/C=C\c2cc(I)c(OC)c(OC)c2)cc1O
Agent: O=P([O-])([O-])[O-]
Product: C(=C\c1ccccc1)\c1ccccc1
Yield: 321.2 %

Procedure:
The phosphorylation reaction used to obtain phosphate 15 was repeated with Z-stilbene 14a (2.39 g, 0.95 mmol) to obtain 0.55 g of Z-stilbene 17 in 86% yield as a colorless oil: b.p. dec. 274° C. (0.01 mmHg); HRMS calc for C31H31PO7 [M+H]+ 673.0852; found [M+H]+, 673.0808. 1H-NMR (300 MHz, CDCl3) δ 3.51 (s, 3H), 3.65 (s, 3H), 3.72 (s, 3H), 5.04 (s, 2H), 5.06 (s, 2H), 6.36 (d, 1H, J=9Hz), 6.42 (d, 1H, J=9Hz), 6.77 (d, 1H, J=1.2 Hz), 6.89 (d, 1H, J=6 Hz), 7.02 (d, 1H, J=6 Hz), 7.01 (s, 1H), 7.19 (d, 1H, J=1.2 Hz), 7.28 (m, 10H); and 13C-NMR (75 MHz, CDCl3) δ 56.20, 56.50, 60.73, 71.18, 71.24, 92.73, 113.72, 114.23, 122.58, 122.61, 128.10, 128.93, 129.50, 129.56, 130.18, 130.85, 130.86, 131.87, 136.26, 136.66, 136.73, 140.32, 140.39, 149.12, 151.21, 151.25, 153.26.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][NH:8][CH2:9]2)=[CH:4][CH:3]=1.[CH:12]([O:15][C:16]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][C:17]=1[C:18](O)=[O:19])([CH3:14])[CH3:13]>>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:18]([C:17]3[CH:21]=[C:22]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:23]=[CH:24][C:16]=3[O:15][CH:12]([CH3:14])[CH3:13])=[O:19])[CH2:9]2)=[CH:4][CH:3]=1
Reactant: Brc1ccc2c(c1)CNCC2
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)O
Product: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCc2ccc(Br)cc2C1

Procedure:
Prepared in analogy to example 1.1 from 7-bromo-1,2,3,4-tetrahydro-isoquinoline (CA [17680-55-6]) and 2-isopropoxy-5-methanesulfonyl-benzoic acid (Example 2.1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-])=O)=[C:6]([O:8][CH3:9])[CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].C(N(CC)CC)C.[C:26](Cl)(=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28]>C(O)C.C(O)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:10][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])=[C:6]([O:8][CH3:9])[CH:7]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: COc1cc(Cl)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCO
Product: COc1cc(Cl)ccc1NC(=O)C(C)(C)C
Temperature: 0 °C
Yield: 96.8 %

Procedure:
A stirred solution of 22.6 g (100 mmol) of stannous chloride dihydrate in 40 mL of absolute ethanol was heated to reflux and treated with 3.75 g (20 mmol) of 5-chloro-2-nitroanisole in 20 mL of 1:1 ethanol-tetrahydrofuran over 3 min. Stirring at reflux for an additional 10 minutes gave a clear solution which was then cooled to 0° C. The mixture was treated with aqueous Na2CO3 until a pH of 8-9 was reached. The colloidal suspension was extracted twice with ethyl acetate, and the combined organic extracts were washed with saturated NaHCO3 then brine. The solution was dried (MgSO4) and concentrated under reduced pressure. The crude oil was dissolved in 40 mL of CH2Cl2 and cooled to 0° C. The solution was treated with 4.2 mL (30 mmol) of triethylamine followed by 2.8 mL (23 mmol) of pivaloyl chloride. After stirring 2 h at 0° C. the mixture was quenched with 0.5N HCl, and the phases were separated. The aqueous phase was extracted with 100 mL of 1:1 ether-hexanes, and the combined organic extracts were washed sequentially with 0.1N HCl, dilute K2CO3, water, and brine. The solution was dried (MgSO4) and concentrated under reduced pressure to give 4.68 g (97%) of 4'-chloro-2'-methoxy-2,2-dimethylpropionanilide as an tan solid, mp 66°-69° C. 1H NMR (300 MHz, CDCl3) δ8.36(d, 1H, J=8.8 Hz); 8.03(br. s, 1H); 6.94(dd, 1H, J=8.8, 2.2 Hz); 6.86(d, 1H, J=2.2 Hz); 3.90(s, 3H); 1.32(s, 9H). High resolution mass spec: calculated for C12H17NO2Cl(M+H)+ : 242.0948, found: 242.0943. Analysis calculated for C12H16NO2Cl: C, 59.63; H, 6.67; N, 5.79; Cl, 14.67. Found: C, 59.73; H, 6.67; N, 5.57; Cl, 14.42.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[N:20]=[C:19]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[N:18]=[C:17]([O:28][CH2:29][CH2:30][C:31]([OH:33])=O)[C:16]=2[O:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[O:41][CH3:42])(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH:43]([C:46]1[CH:52]=[CH:51][CH:50]=[CH:49][C:47]=1[NH2:48])([CH3:45])[CH3:44]>>[CH:43]([C:46]1[CH:52]=[CH:51][CH:50]=[CH:49][C:47]=1[NH:48][C:31](=[O:33])[CH2:30][CH2:29][O:28][C:17]1[C:16]([O:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[O:41][CH3:42])=[C:15]([NH:14][S:11]([C:8]2[CH:7]=[CH:6][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:10][CH:9]=2)(=[O:12])=[O:13])[N:20]=[C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)[N:18]=1)([CH3:45])[CH3:44]
Reactant: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(N2CCN(C)CC2)nc1OCCC(=O)O
Reactant: CC(C)c1ccccc1N
Product: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(N2CCN(C)CC2)nc1OCCC(=O)Nc1ccccc1C(C)C

Procedure:
The procedure described in Example 2 was repeated by use of 3-[6-(4-t-butylphenylsulfonylamino)-5-(2-methoxyphenoxy)-2-(4-methylpiperazinyl)-4-pyrimidinyloxy]propionic acid and 2-isopropylaniline, to thereby obtain the title compound as a pale yellow solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[CH2:10]([O:12][C:13](=[O:24])[CH2:14][CH:15]([NH2:23])[C:16]1([CH3:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH3:11].C(N(CC)C(C)C)(C)C>C1COCC1.CO>[Cl:1][C:2]1[N:7]=[C:6]([NH:23][CH:15]([C:16]2([CH3:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][C:13]([O:12][CH2:10][CH3:11])=[O:24])[C:5]([F:9])=[CH:4][N:3]=1
Reactant: CCOC(=O)CC(N)C1(C)CCCCC1
Reactant: Fc1cnc(Cl)nc1Cl
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCOC(=O)CC(Nc1nc(Cl)ncc1F)C1(C)CCCCC1
Temperature: 95 °C

Procedure:
A mixture of 2,4-dichloro-5-fluoro-pyrimidine (1.83 g, 85.33 mmol), racemic ethyl-3-amino-3-(1-methylcyclohexyl)propanoate, 205a, (2.34 g, 11.0 mmol) and N,N-diisopropylethylamine (4.79 g, 27.50 mmol) in THF (40 mL) and methanol (10 mL) was heated at 95° C. for 3 hours. The solution was cooled to room temperature and the solvent was evaporated under reduced pressure. The crude residue was purified by silica gel chromatography (0-60% EtOAc/Hexanes gradient) to afford 620 mg of the desired product as a white foamy solid: 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J=2.6 Hz, 1H), 5.37 (m, 1H), 4.59 (m, 1H), 4.00 (q, 7.2 Hz, 2H), 2.62 (dd, J=14.7, 3.8 Hz, 1H), 1.67 (m, 1H), 1.17 (m, 10H), 1.10 (t, J=7.1 Hz, 3H), 0.85 (s, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.69 minutes (M+H) 344.39.
Reaction SMILES: [CH2:1]([N:8]=[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[K])(C)(C)C>C(O)=O.CCN(CC)CC>[CH2:1]([NH:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=NCc1ccccc1)c1ccccc1
Agent: CC(C)(C)O[K]
Solvent: O=CO
Solvent: CCN(CC)CC
Product: CC(NCc1ccccc1)c1ccccc1
Reaction time: 24 h
Yield: 23 %

Procedure:
The catalyst of formula 1.3 (10 μmol) was added to N-benzyl acetophenone imine (1 mmol) and tBuOK (5.6 mg, 50 μmol) was added too. Now 0.5 ml of a HCO2H/Et3N (3:2) mixture was added and the solution was stirred under nitrogen at 400 C for 24 h. After 36 h at ambient temperature 23% N-benzyl-1-phenylethylamine had formed.
Reaction SMILES: [C:1]([O:20][CH:21]1[CH2:25][C:24](=[O:26])[CH:23]=[CH:22]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[I-].[Li+].COC(C)(C)C>C1(C)C=CC=CC=1>[C:1]([O:20][C@@H:21]1[CH2:25][C@H:24]([OH:26])[CH:23]=[CH:22]1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1C=CC(OC(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Agent: [Al+3]
Agent: [H-]
Agent: [I-]
Solvent: Cc1ccccc1
Solvent: COC(C)(C)C
Product: O[C@@H]1C=C[C@H](OC(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Temperature: -20 °C
Reaction time: 1 h
Yield: 94.5 %

Procedure:
A slurry of 4-trityloxy-2-cyclopentenone (1.03 g, 3.03 mmol, prepared in example 27) in toluene (8 mL) is cooled to -20° C. and treated sequentially with lithium aluminum hydride (76 mg, 2.0 mL), lithium iodide (1.06 g, 7.9 mmol) and dropwise with tert-butyl methyl ether (2 mL, over 5 minutes). The reaction is stirred for 1 hour at -20° C., warmed to 0° C. over 30 minutes, and stirred at 0° C. to 15° C. for 4 hours. The reaction is quenched by slow addition of 1N NaOH (2 mL) and then the reaction is filtered. The solids are washed with tert-butyl methyl ether and the phases of the filtrate are separated. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue is purified by column chromatography (silica gel, 20% ethyl acetate/hexane) to provide the title compound as a white foam (980 mg, 95%). 1H NMR (CDCl3) δ7.5 (m, 6H), 7.3 (m, 9H), 5.79 (d, 1H), 5.14 (d, 1H), 4.5 (m, 1H), 4.4 (m, 1H), 2.2 (m, 1H), 1.42 (d, 1H); 13C NMR (CDCl3) δ145.1, 136.2, 135.9, 129.0, 128.1, 127.3, 87.7, 77.4, 74.9, 43.2; IR (KBr) νmax 3422, 3057, 1491, 1364, 1084, 1065, 1024 cm-1.