Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:4]([F:15])[CH:3]=1.[N:16]([CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])=[N+:17]=[N-:18]>C1C=CC=CC=1>[CH2:13]([O:12][C:10]([C:9]1[N:16]([CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:17]=[N:18][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[F:15])=[O:11])[CH3:14]
Reactant: CCOC(=O)C#Cc1ccc(Br)cc1F
Reactant: C[Si](C)(C)CN=[N+]=[N-]
Solvent: c1ccccc1
Product: CCOC(=O)c1c(-c2ccc(Br)cc2F)nnn1C[Si](C)(C)C
Temperature: 90 °C
Reaction time: 4 h

Procedure:
In a 50 mL pear-shaped flask, ethyl 3-(4-bromo-2-fluorophenyl)propiolate (1.27 g, 4.68 mmol) and (azidomethyl)trimethylsilane (2.42 g, 2.78 mL, 18.7 mmol, Eq: 4) were combined with benzene (3.5 mL) to give a light yellow solution. The reaction mixture was heated to 90° C. and stirred for 4 h. The reaction mixture was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 20% EtOAc in heptane) to afford 616 mg (33%) of the desired less polar regio-isomer as a white solid. (M+H)+=400.0/402.0 m/e.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([NH2:13])[CH:7]=1.C([O:17][C:18](=O)[CH:19]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=1)[C:20](=O)[CH:21]([CH3:23])[CH3:22])C.O1CCOCC1>O>[CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]2[C:7]=1[C:18](=[O:17])[C:19]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]([S:32]([CH3:35])(=[O:33])=[O:34])=[CH:30][CH:31]=1)=[C:20]([CH:21]([CH3:22])[CH3:23])[NH:13]2
Reactant: CCOC(=O)C(Cc1ccc(S(C)(=O)=O)cc1)C(=O)C(C)C
Reactant: COC(=O)COc1ccc(Cl)c(N)c1
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)COc1ccc(Cl)c2[nH]c(C(C)C)c(Cc3ccc(S(C)(=O)=O)cc3)c(=O)c12
Temperature: 120 °C

Procedure:
A mixture of (3-amino-4-chlorophenoxy)acetic acid methyl ester (0.70 g), 2-(4-methanesulfonylbenzyl)-4-methyl-3-oxopentanoic acid ethyl ester (1.4 g), polyphosphoric acid (3.5 g) and dioxane (50 mL) was heated at 120° C. for 2 days. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (1:1 by volume) to afford title compound. 0.79 g.
Reaction SMILES: C(O[C:6]([NH:8][C@@H:9]([CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[N:30])[CH:24]=1)[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])(C)(C)C.[C:31]([C:33]1[CH:41]=[CH:40][C:36](C(O)=O)=[CH:35][CH:34]=1)#[N:32].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl>Cl.O1CCOCC1.C(Cl)Cl>[C:31]([C:33]1[CH:41]=[CH:40][C:36]([C:6]([NH:8][C@@H:9]([CH2:20][CH2:21][O:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[N:30])[CH:24]=2)[C:10]([O:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:11])=[O:7])=[CH:35][CH:34]=1)#[N:32]
Reactant: N#Cc1ccc(C(=O)O)cc1
Reactant: CC(C)(C)OC(=O)N[C@@H](CCOc1cccc(C#N)c1)C(=O)OCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: N#Cc1ccc(C(=O)N[C@@H](CCOc2cccc(C#N)c2)C(=O)OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1.12 g (2.73 mmol) of benzyl (2S)-2-t-butoxycarbonylamino-4-(3-cyanophenoxy)butanoate was dissolved in 10 ml of 4 N solution of hydrogen chloride in dioxane, and they were stirred at room temperature for 2 hours. The solvent was evaporated, and the obtained oily residue was dissolved in 14 ml of dichloromethane. 390 mg (2.73 mmol) of 4-cyanobenzoic acid, 405 mg (3.00 mmol) of HOBt, 0.83 ml (6.00 mmol) of triethylamine and 575 mg (3.00 mmol) of WSC.HCl were successively added to the solution under cooling with ice, and they were stirred at room temperature overnight. After the treatment with methylene chloride as the extractant in an ordinary manner, the title compound was obtained.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[C:12]2[C:11](=[O:13])[N:10]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:9]=[CH:8][C:7]=2[N:6]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:5]=1.[CH3:30]C(C)([O-])C.[Na+].CI>O>[CH3:30][O:1][CH2:2][CH2:3][C:4]1[C:12]2[C:11](=[O:13])[N:10]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:19])([CH3:20])[CH3:21])[N:9]=[CH:8][C:7]=2[N:6]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:27])[CH3:29])[CH:5]=1
Reactant: C[Si](C)(C)CCOCn1ncc2c(c(CCO)cn2COCC[Si](C)(C)C)c1=O
Reactant: CC(C)(C)[O-]
Agent: [Na+]
Solvent: O
Solvent: CI
Product: COCCc1cn(COCC[Si](C)(C)C)c2cnn(COCC[Si](C)(C)C)c(=O)c12
Reaction time: 2 h
Yield: 88.8 %

Procedure:
To 5 ml of mixed solvent (dehydrated tetrahydrofuran:N,N-dimethylformamide=3:1 (V/V)) solution containing 1.29 g (2.93 mmol) of 3-(2-hydroxyethyl)-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 57-(e) was added 0.56 g (5.83 mmol) of sodium tert-butoxide under room temperature, and the mixture was stirred at the same temperature for 2 hours. Then, 1.1 ml (17.7 mmol) of methyl iodide was added to the mixture, and the mixture was further stirred for 16-hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then, concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=1:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 1.18 g of the title compound as a slightly yellowish oil. (Yield: 89%)
Reaction SMILES: COC(N([C@@H](C1C=CC=CC=1)C)C(=O)[CH:7]([CH2:14][CH:15]=[CH2:16])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])=O.[CH3:26][O-:27].[Na+].[CH3:29][OH:30]>>[CH2:11]([CH:10]([CH2:9][CH2:8][CH2:7][CH2:14][CH2:15][CH3:16])[C:26]([O:30][CH3:29])=[O:27])[CH:12]=[CH2:13]
Reactant: C[O-]
Reactant: CO
Reactant: C=CCC(CCCCCC)C(=O)N(C(=O)OC)[C@H](C)c1ccccc1
Agent: [Na+]
Product: C=CCC(CCCCCC)C(=O)OC
Reaction time: 22 h
Yield: 51 %

Procedure:
A solution of 0.345 g (1.0 mmol) of N-methyloxycarbonyl-N-(2-allyloctanoyl)-1-(R)-phenylethylamine in 5 ml of methanol was cooled to 0° C., 0.386 g (2.0 mmol) of NaOMe (28% solution in methanol) was added, and the mixture was stirred for 22 hours. The reaction was terminated by addition of 2 ml of 1 N hydrochloric acid, and the product was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was isolated/purified on a silica gel column to give 0.10 g (51%) of the title compound. N-(2-Allyloctanoyl)-(R)-1-phenylethylamine was formed as a byproduct in 45% yield.
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][CH3:12])=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[NH2-].[Na+].C1([O:21][C:22](=O)[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)C=CC=CC=1>O1CCCC1>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][CH3:12])=[CH:8][CH:9]=2)[CH2:4][CH:3]1[C:22](=[O:21])[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1
Reactant: COc1ccc(C(=O)Oc2ccccc2)cc1
Reactant: COc1ccc2c(c1)CCC2=O
Agent: [NH2-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(C(=O)C2Cc3cc(OC)ccc3C2=O)cc1
Temperature: 0 °C
Yield: 51 %

Procedure:
A solution of 22.2 g (137 mmol) of 1-oxo-5-methoxyindane in tetrahydrofuran was added dropwise to a cold suspension of 11 g (274 mmol) of sodium amide in tetrahydrofuran. The resulting mixture was stirred for ten minutes and a solution of 31.3 g (137 mmol) of phenyl-4-methoxybenzoate in tetrahydrofuran was added. Cooling was discontinued and a slight exothermic reaction occurred. The mixture was stirred at ambient temperature for an additional two hours. A thick precipitate developed and the reaction mixture was poured into ice-water. The aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was evaporated to dryness to obtain 20.7 g of the title compound. mp: 160° C.-162° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:15]=[C:14]([O:16][C:17]2[CH:18]=[N:19][C:20]([C:23](=[O:27])[N:24]([CH3:26])[CH3:25])=C[CH:22]=2)[C:8]2[CH2:9][C:10]([CH3:13])([CH3:12])[O:11][C:7]=2[CH:6]=1)=[O:4].C[N:29](C)C(C1N=CC(Br)=CN=1)=O.COC(C1C=C(O)C2CC(C)(C)OC=2C=1)=O>>[CH3:1][O:2][C:3]([C:5]1[CH:15]=[C:14]([O:16][C:17]2[CH:22]=[N:29][C:20]([C:23](=[O:27])[N:24]([CH3:25])[CH3:26])=[N:19][CH:18]=2)[C:8]2[CH2:9][C:10]([CH3:12])([CH3:13])[O:11][C:7]=2[CH:6]=1)=[O:4]
Reactant: COC(=O)c1cc(Oc2ccc(C(=O)N(C)C)nc2)c2c(c1)OC(C)(C)C2
Reactant: CN(C)C(=O)c1ncc(Br)cn1
Agent: COC(=O)c1cc(O)c2c(c1)OC(C)(C)C2
Product: COC(=O)c1cc(Oc2cnc(C(=O)N(C)C)nc2)c2c(c1)OC(C)(C)C2

Procedure:
The title compound was prepared in a similar manner as described for Intermediate 161b, from 5-bromo-pyrimidine-2-carboxylic acid dimethylamide (164a) (271 mg, 1.18 mmol) and 4-hydroxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester (3e) (262 mg, 1.18 mmol) to give a white foam (110 mg, 25% yield). 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 2 H) 7.24-7.36 (m, 1 H) 7.20 (s, 1 H) 3.88 (s, 3 H) 3.17 (s, 3 H) 3.00 (s, 3 H) 2.95 (s, 2 H) 1.51 (s, 6 H); LCMS for C19H21N3O5 m/z 372.00 (M+H+).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[OH:12])[CH:7]=[O:8])[CH3:2].C(=O)([O-])[O-].[K+].[K+].I[CH2:20][CH3:21]>CN(C)C=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[O:12][CH2:20][CH3:21])[CH:7]=[O:8])[CH3:2]
Reactant: CCOc1cc(C=O)ccc1O
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOc1ccc(C=O)cc1OCC
Reaction time: 0.17 h
Yield: 93.5 %

Procedure:
3-Ethoxy-4-hydroxy-benzaldehyde (Aldrich, 100 g, 0.602 mole) was dissolved in N,N-dimethylformamide (1 L). The reaction was placed under N2. Solid potassium carbonate (103 g, 0.662 moles) was added and the reaction was stirred 10 minutes. Iodoethane (175 g, 1.26 moles) was added and the reaction was stirred for 16 hours at room temperature. The reaction was monitored by thin-layer chromatography which indicated complete consumption of the phenol to give a new product. The reaction was filtered to remove the potassium carbonate and solvent removed in vacuo. The residue was dissolved in methylene chloride and filtered. Silica gel (200 g) was added and the dichloromethane removed in vacuo. The crude product absorbed on silica gel was submitted to flash chromatography (hexane, 100%, 2L, then ethyl acetate:hexane, 1:3, 2L, then ethyl acetate:hexane, 1:1) to yield 109.36 g of 3,4-diethoxy-benzaldehyde HNMR (CDCl3): 9.83 (s, 1H), 7.41 (m, 2H), 6.96 (d, 1H), 4.17 (m, 4H), 1.50 (t, 3H) 1.47 (t, 3H).
Reaction SMILES: [CH:1]1([NH:7][C:8]([C:10]2[N:11]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)=[CH:18][CH:17]=3)[N:12]=[C:13]([CH3:15])[CH:14]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:29]1(=O)[CH2:33][CH2:32][CH2:31][CH2:30]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:1]1([NH:7][C:8]([C:10]2[N:11]([C:16]3[CH:17]=[CH:18][C:19]([O:22][CH:23]4[CH2:24][CH2:25][N:26]([CH:29]5[CH2:33][CH2:32][CH2:31][CH2:30]5)[CH2:27][CH2:28]4)=[CH:20][CH:21]=3)[N:12]=[C:13]([CH3:15])[CH:14]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C1CCCC1
Reactant: Cc1cc(C(=O)NC2CCCCC2)n(-c2ccc(OC3CCNCC3)cc2)n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: Cc1cc(C(=O)NC2CCCCC2)n(-c2ccc(OC3CCN(C4CCCC4)CC3)cc2)n1
Reaction time: 1 h
Yield: 3.4 %

Procedure:
To a solution of 5-methyl-2-[4-(piperidin-4-yloxy)phenyl]-2H-pyrazole-3-carboxylic acid cyclohexylamide (60 mg, 0.157 mmol) in methylene chloride (9 mL) was added cyclopentanone (21 μL, 0.24 mmol) and acetic acid (150 μL). After 1 hour at room temperature, sodium triacetoxyborohydride (51 mg, 0.24 mmol) was added and the reaction was allowed to stir for an additional 4 hours. The reaction was quenched with 10% NaOH and extracted with methylene chloride. The methylene chloride solution was dried (MgSO4) and concentrated. The residue was purified by semi-prep LC-MS to give 2.4 mg of the desired product. LC-MS (C27H38N4O2 calculated 450) m/z 451 (M+H); 1H NMR (300 MHz, CDCl3) 7.34-7.31 (m, 2H), 7.01-6.98 (m, 2H), 6.78 (d, J=8.4 Hz, 1H), 6.70 (s, 1H), 4.42 (m, 1H), 3.95-3.93 (m, 1H), 2.87-2.83 (m, 2H), 2.68-2.54 (m, 3H), 2.23 (s, 3H), 2.15-1.14 (m, 22H).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[N:8][N:7]([C@@H:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[C:19]([F:22])([F:21])[F:20])[CH3:11])[C:6]=2[CH:23]=1.C(O[C:29]([N:31]1[CH2:36][CH:35]=[C:34](B(O)O)[CH2:33][CH2:32]1)=[O:30])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>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.C1(C)C=CC=CC=1.C(O)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C@H:10]([N:7]2[C:6]3[CH:23]=[C:2]([C:34]4[CH2:33][CH2:32][N:31]([C:29]([C@H:32]5[CH2:33][CH2:34][CH2:35][CH2:36][NH:31]5)=[O:30])[CH2:36][CH:35]=4)[CH:3]=[CH:4][C:5]=3[N:9]=[N:8]2)[CH3:11])=[C:13]([C:19]([F:22])([F:21])[F:20])[CH:14]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(B(O)O)CC1
Reactant: C[C@H](c1ccc(Cl)cc1C(F)(F)F)n1nnc2ccc(Br)cc21
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: Cc1ccccc1
Solvent: CCO
Product: C[C@H](c1ccc(Cl)cc1C(F)(F)F)n1nnc2ccc(C3=CCN(C(=O)[C@H]4CCCCN4)CC3)cc21
Temperature: 100 °C
Yield: 162.5 %

Procedure:
A mixture of (R)-6-bromo-1-(1-(4-chloro-2-(trifluoromethyl)phenyl)ethyl)-1H-benzo[d][1,2,3]triazole (0.32 g, 0.8 mmol), (N-t-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)boronic acid pincol ester (0.27 g, 0.8 mmol), Pd(PPh3)4 (0.046 g, 0.039 mmol), and 2 M aqueous potassium carbonate (1.2 mL, 2.4 mmol) in 2:1 toluene/ethanol (3.6 mL) was purged with nitrogen for 5 min, and then heated at 100° C. for 2 h. After cooling to room temperature, the mixture was extracted with ethyl acetate (15 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated in vacuo. The resulting crude material was purified by flash chromatography (SiO2, 0-100% ethyl acetate in hexanes) to afford the desired product (0.33 g, 0.65 mmol, 83%).
Reaction SMILES: I[C:2]1[C:3]([CH:11]([CH3:13])[CH3:12])=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=12.[O:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=2)[CH2:16][CH2:15]1.C(C1C(C2C=C(N)C=CC=2)=C2C=CC=CN2N=1)(C)C>>[CH:11]([C:3]1[C:2]([C:23]2[CH:22]=[CH:21][C:20]([N:17]3[CH2:16][CH2:15][O:14][CH2:19][CH2:18]3)=[CH:25][CH:24]=2)=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1)([CH3:13])[CH3:12]
Reactant: CC(C)c1nn2ccccc2c1I
Reactant: OB(O)c1ccc(N2CCOCC2)cc1
Agent: CC(C)c1nn2ccccc2c1-c1cccc(N)c1
Product: CC(C)c1nn2ccccc2c1-c1ccc(N2CCOCC2)cc1

Procedure:
2-Isopropyl-3-(4-morpholin-4-yl-phenyl)-pyrazolo[1,5-a]pyridine was prepared from 3-iodo-2-isopropyl-pyrazolo[1,5-a]pyridine and 4-morpholinophenylboronic acid following the method used in Step 3 of the synthesis of 3-(2-Isopropyl-pyrazolo[1,5-a]pyridin-3-yl)-phenylamine (Example 59) (157 mg, 16%). 1H-NMR (250 MHz, DMSO-d6) δ 8.61 (d, J=6.3 Hz, 1H), 7.45 (d, J=9.0 Hz, 1H), 7.30 (d, J=7.0 Hz, 2H), 7.15-7.06 (m, 3H), 6.81 (t, J=6.5 Hz, 1H), 3.79-3.75 (m, 4H), 3.25 (sept, J=6.3 Hz, 1H), 3.22-3.15 (m, 4H), 1.27 (d, J=6.8 Hz, 6H); LC/MS 322.3 m/z (M+H+). Compound 1102.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][I:10].[C:11]1([P:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1(C)C=CC=CC=1>[I-:10].[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][P+:17]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: Brc1ccccc1CCI
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Brc1ccccc1CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [I-]
Temperature: 100 °C
Yield: 75.7 %

Procedure:
To a solution of 1-bromo-2-(2-iodoethyl)benzene (0.3244 g, 1.043 mmol) in toluene (1.739 ml) in a pressure tube was added triphenylphosphine (0.274 g, 1.043 mmol) and the tube was sealed and stirred at 100° C. The mixture was cooled to room temperature. The product solidified and the solvent was decanted off. The solid was taken up in DCM and concentrated to give the title compound (0.4526 g, 0.790 mmol, 76% yield) as a white foam. LCMS (M+H) calcd for C26H24BrP: 447.07. found: 448.0.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[C:15]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]>>[N+:12]([C:3]1[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=1[N:25]1[CH2:24][CH2:23][N:22]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:27][CH2:26]1)([O-:14])=[O:13]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)ccc1F
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)cc2[N+](=O)[O-])CC1
Yield: 99 %

Procedure:
Method 1 was followed using 1-fluoro-2-nitro-4-(trifluoromethyl)benzene (1.0 eq), 1-Boc-piperazine (1.2 eq), and TEA (2.0 eq) at 55° C. for 1 hour yielding tert-butyl 4-(2-nitro-4-(trifluoro-methyl)phenyl)piperazine-1-carboxylate (99%). LCMS (m/z): 376.1 (MH+); LC Rt=3.58 min.
Reaction SMILES: N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[NH2:17][C:18]1[N:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)=[CH:20][C:19]=1[C:31]1[O:32][C:33]2[C:38]([N:39]=1)=[CH:37][CH:36]=[CH:35][N:34]=2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:59]1([CH2:64][CH2:65][CH2:66]O)[CH2:63][CH2:62][CH2:61][CH2:60]1>ClCCl.CN(C=O)C>[N:39]1[C:38]2[C:33](=[N:34][CH:35]=[CH:36][CH:37]=2)[O:32][C:31]=1[C:19]1[C:18]([NH2:17])=[N:23][CH:22]=[C:21]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH2:66][CH2:65][CH2:64][N:59]3[CH2:63][CH2:62][CH2:61][CH2:60]3)=[CH:26][CH:25]=2)[CH:20]=1
Reactant: OCCCN1CCCC1
Reactant: Nc1ncc(-c2ccc(O)cc2)cc1-c1nc2cccnc2o1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Nc1ncc(-c2ccc(OCCCN3CCCC3)cc2)cc1-c1nc2cccnc2o1
Temperature: 25 °C
Reaction time: 2 h
Yield: 26.4 %

Procedure:
A solution of di-tert-butyl azodicarboxylate (DTAD) (227 mg) in dichloromethane (1 ml) was added to a stirred solution of 4-(6-amino-5-oxazolo[5,4-b]pyridin-2-yl-3-pyridyl)phenol (100 mg), polystyrene bound triphenylphosphine (330 mg, 3 mmol/g) and 3-pyrrolidin-1-ylpropan-1-ol (64 mg) in DMF (2 ml) at room temperature under argon. The resulting suspension was stirred at room temperature for 2 hours. The mixture was filtered and the resulting solid was washed with methanol. The filtrates were combined, concentrated to dryness and diluted with DCM/TFA (1 ml: 1 ml). The mixture was stirred for 30 min and concentrated. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 micron silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 1% acetic acid) and Methanol as eluent. The fractions containing the desired compound were evaporated to dryness to afford 3-oxazolo[5,4-b]pyridin-2-yl-5-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyridin-2-amine (36 mg) as a solid. NMR Spectrum: (DMSOd6) 1.86 (bs, 4H), 2.03-2.15 (m, 2H), 3.02-3.33 (m partially hidden by H2O, 6H), 4.11 (t, 2H), 7.06 (d, 2H), 7.53 (dd, 1H), 7.68 (d, 2H), 7.77 (bs, 2H), 8.30 (dd, 1H), 8.40 (dd, 1H), 8.46 (d, 1H), 8.58 (d, 1H); Mass spectrum: M+H+ 416. The 4-(6-amino-5-oxazolo[5,4-b]pyridin-2-yl-3-pyridyl)phenol used as starting material was made as follows:
Reaction SMILES: [CH:1]([N:4]1[C:10]2[CH:11]=[C:12]([N+:15]([O-])=O)[CH:13]=[CH:14][C:9]=2[C:8](=[O:18])[NH:7][CH2:6][CH2:5]1)([CH3:3])[CH3:2].C(O)C.C(Cl)Cl>[Pd].CO>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]2[C:8](=[O:18])[NH:7][CH2:6][CH2:5][N:4]([CH:1]([CH3:2])[CH3:3])[C:10]=2[CH:11]=1
Reactant: CC(C)N1CCNC(=O)c2ccc([N+](=O)[O-])cc21
Agent: [Pd]
Solvent: ClCCl
Solvent: CCO
Solvent: CO
Product: CC(C)N1CCNC(=O)c2ccc(N)cc21
Temperature: 25 °C
Reaction time: 64 h
Yield: 61.3 %

Procedure:
To a 500 ml round bottom flask, 1-isopropyl-8-nitro-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (4.10 g, 16 mmoles), ethanol (300 ml), and palladium (320 mg) were added. The mixture was evacuated and charged with hydrogen (3 times). The reaction was stirred at room temperature under hydrogen balloon for the weekend (64 hrs). The solid was filtered through celite and washed with methanol. The solvent was then removed under vacuum to afford a brown oil. The desired product (2.15 g, 60% yield) was isolated via column chromatography with DCM and methanol as eluant (0 to 25% methanol). NMR 1H-(DMSO)-δ-7.32-7.52 (m, 1H), 7.00 (bs, 1H), 6.80 (bs, 1H), 4.80 (p, 1H), 3.40 (bs, 4H), 1.10 (d, 6H, J=6.58 Hz)
Reaction SMILES: [S:1]1[CH2:5][C:4](=[O:6])[NH:3][C:2]1=[O:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[F:43][C:44]1[CH:52]=[C:51]2[C:47]([C:48](=[CH:54][C:55]3[NH:56][CH:57]=[C:58]([CH2:60][N:61]4[CH2:66][CH2:65][O:64][CH2:63][CH2:62]4)[CH:59]=3)[C:49](=[O:53])[NH:50]2)=[CH:46][C:45]=1[CH2:67]O.N(C(OC(C)(C)C)=O)=NC([O-])=O>C1COCC1.CC#N>[F:43][C:44]1[CH:52]=[C:51]2[C:47]([C:48](=[CH:54][C:55]3[NH:56][CH:57]=[C:58]([CH2:60][N:61]4[CH2:62][CH2:63][O:64][CH2:65][CH2:66]4)[CH:59]=3)[C:49](=[O:53])[NH:50]2)=[CH:46][C:45]=1[CH2:67][N:3]1[C:4](=[O:6])[CH2:5][S:1][C:2]1=[O:7]
Reactant: O=C1Nc2cc(F)c(CO)cc2C1=Cc1cc(CN2CCOCC2)c[nH]1
Reactant: O=C1CSC(=O)N1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: CC(C)(C)OC(=O)N=NC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CC#N
Product: O=C1Nc2cc(F)c(CN3C(=O)CSC3=O)cc2C1=Cc1cc(CN2CCOCC2)c[nH]1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
Thiazolidine-2,4-dione (0.350 mmol) and triphenylphosphine on resin (1.66 mmol/g, 0.415 mmol) are stirred for 10 min. at ambient temperature in anhydrous THF (9 ml) under nitrogen. The mixture is cooled in an ice bath and di-tert-butyl azodicarboxylate (0.369 mmol) is added all at once. The mixture is stirred at 0° C. for 10 min, and then the compound obtained in Step D (0.238 mmol) is added all at once. The mixture is stirred at 0° C. for 1.5 hours, and then thiazolidine-2,4-dione (0.350 mmol), three portions of triphenylphosphine on resin (1.66 mmol/g; 0.166 mmol, 0.415 mmol and 0.166 mmol) and three portions of tert-butyl azodicarboxylate (each portion 0.369 mmol) are added over a period of 48 hours. Silica gel is added and the mixture is evaporated in vacuo. The residue obtained is purified by flash chromatography (DCM/MeOH 100:0 to 95:5) to yield a dark yellow solid which, after trituration in CH3CN, yields the title product in the form of a yellow solid.