Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:8][C:9]1[C:17]2[N:16]=[C:15]([CH2:18][CH2:19][CH2:20][CH3:21])[N:14]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]4[C:30]([C:35]([OH:37])=[O:36])=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:25][CH:24]=3)[C:13]=2[C:12]([CH3:38])=[CH:11][CH:10]=1)C1C=CC=CC=1.[H][H]>CO.CN(C)C=O.[OH-].[OH-].[Pd+2]>[CH2:18]([C:15]1[N:14]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([C:29]3[C:30]([C:35]([OH:37])=[O:36])=[CH:31][CH:32]=[CH:33][CH:34]=3)=[CH:27][CH:28]=2)[C:13]2[C:12]([CH3:38])=[CH:11][CH:10]=[C:9]([OH:8])[C:17]=2[N:16]=1)[CH2:19][CH2:20][CH3:21]
Reactant: CCCCc1nc2c(OCc3ccccc3)ccc(C)c2n1Cc1ccc(-c2ccccc2C(=O)O)cc1
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CO
Product: CCCCc1nc2c(O)ccc(C)c2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared in analogous manner to Example 57 from 4'-[(4-benzyloxy-2-n-butyl-7-methyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylic acid and hydrogen in methanol/dimethylformamide in the presence of 20% palladium hydroxide on carbon.
Reaction SMILES: I[C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH:9]#[C:10][CH2:11][CH2:12][CH3:13].C(N(CC)CC)C>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu](I)I.C(#N)C>[C:9]([C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4])#[C:10][CH2:11][CH2:12][CH3:13]
Reactant: C#CCCC
Reactant: Nc1ccccc1I
Agent: Cl[Pd]Cl
Agent: I[Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCC#Cc1ccccc1N
Temperature: 25 °C
Reaction time: 2 h
Yield: 68.9 %

Procedure:
A mixture of 2-iodoaniline (500 mg, 2.28 mmol), 1-pentyne (0.27 mL, 2.74 mmol), bis(triphenylphosphine)palladium (II) chloride (77 mg, 0.11 mmol), copper iodide (21 mg, 0.11 mmol), triethylamine (0.95 mL, 6.84 mmol), and acetonitrile (10 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. The residue was stirred in diethyl ether and filtered. The filtrate was concentrated under reduced pressure to afford 0.25 g of 2-pent-1-ynylaniline.
Reaction SMILES: CN(C)CCN.[CH:7]1([CH2:13][O:14][N:15]2C(=O)C3=CC=CC=C3C2=O)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.C(O)(=O)C.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][S:38]([C:41]([F:44])([F:43])[F:42])(=[O:40])=[O:39])=[C:33]([C:45](=O)[CH2:46][CH3:47])[CH:32]=1>CCO>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][S:38]([C:41]([F:44])([F:43])[F:42])(=[O:40])=[O:39])=[C:33]([C:45](=[N:15][O:14][CH2:13][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:46][CH3:47])[CH:32]=1
Reactant: CCC(=O)c1cc(Cl)ccc1NS(=O)(=O)C(F)(F)F
Reactant: O=C1c2ccccc2C(=O)N1OCC1CCCCC1
Agent: CN(C)CCN
Solvent: CCO
Solvent: CC(=O)O
Product: CCC(=NOCC1CCCCC1)c1cc(Cl)ccc1NS(=O)(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.5 %

Procedure:
N,N-Dimethylethylenediamine (1.53 mL, 13.18 mmol) was added to a solution of N-(cyclohexylmethoxy)phthalimide (2.33 g, 8.99 mmol) in EtOH (30 mL), and the reaction allowed to stir at RT for 2 hours. Glacial acetic acid (5 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of N-(4-chloro-2-propionylphenyl)trifluoromethanesulfonamide 22 (1.89 g, 5.99 mmol) in EtOH (10 mL), and the reaction stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in Et2O (50 mL) and washed with water, brine, dried over MgSO4 and the solvent removed under reduced pressure. The residue was purified by column chromatography (eluting with CH2Cl2/PE, 3:4 to 1:3) to afford N-[4-chloro-2-(1-cyclohexylmethoxyiminopropyl)phenyl]trifluoromethanesulfonamide 104 (2.34 g, 91%), as colorless crystals. 1H n.m.r. (400 MHz, CDCl3) δ 12.01, br s, 1H; 7.67, d, J=8.8 Hz, 1H; 7.48, d, J=2.4 Hz, 1H; 7.32, dd, J=2.4 and 8.8 Hz, 1H; 4.02, d, J=6 Hz, 2H; 2.81, q, J=7.6Hz, 2H; 1.74, m, 6H; 1.27, m, 3H; 1.19, t, J=7.6Hz, 3H; 1.01, m, 2H. HRMS (M+) 426.0971.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[O:12][C:13]=2[C:14]2[CH:19]=[CH:18][CH:17]=[C:16](C#N)[CH:15]=2)[CH:5]=[C:6](F)[CH:7]=1.BrC1C=C(C(OCC)=O)OC=1C1C=CC=C([Cl:39])C=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[O:12][C:13]=2[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:39])[CH:15]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc(-c2cc(F)cc(Cl)c2)c(-c2cccc(C#N)c2)o1
Reactant: CCOC(=O)c1cc(Br)c(-c2cccc(Cl)c2)o1
Product: CCOC(=O)c1cc(-c2cccc(Cl)c2)c(-c2cccc(Cl)c2)o1

Procedure:
The preparation of the title compound takes place in analogy to the synthesis of the compound from Example 11A starting with the compound from Example 5A. Extraction is carried out with dichloromethane and purification is by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient). 452 mg (34% of theory) of the title compound are obtained.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]([CH3:13])[C:5]2[C:10]([N:11]=1)=[CH:9][N:8]=[C:7]([CH3:12])[N:6]=2.[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]2[NH:22][CH:23]=[CH:24][N:25]=2)[N:16]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[F:14][C:15]1[N:16]=[C:17]([C:21]2[N:25]([CH2:2][C:3]3[N:4]([CH3:13])[C:5]4[C:10]([N:11]=3)=[CH:9][N:8]=[C:7]([CH3:12])[N:6]=4)[CH:24]=[CH:23][N:22]=2)[CH:18]=[CH:19][CH:20]=1
Reactant: Fc1cccc(-c2ncc[nH]2)n1
Reactant: Cc1ncc2nc(CCl)n(C)c2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ncc2nc(Cn3ccnc3-c3cccc(F)n3)n(C)c2n1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of 8-Chloromethyl-2,9-dimethyl-9H-purine (40 mg, 0.2 mmol), 2-Fluoro-6-(1H-imidazol-2-yl)-pyridine (40 mg, 0.25 mmol) and K2CO3 (55 mg, 0.4 mmol) in 2 mL of DMF is stirred at room temperature for four hours. The mixture is diluted with water (10 mL), and extracted with ethyl acetate three times. The combined extract is washed with brine, dried and concentrated. The residue is purified by preparative thin layer chromatography to give the title compound. 1H NMR (CDCl3): δ 8.92 (s, 1H), 8.18 (dd, 1H), 7.88 (q, 1H), 7.25 (s, 1H), 7.20 (s, 1H), 7.11 (s, 1H), 6.83 (dd, 1H), 6.22 (s, 2H), 3.89 (s, 3H), 2.8 (s, 3H). LRMS calcd 323. found 324 (MH+).
Reaction SMILES: O[C:2]([C@H:5]1[CH2:8][C@@H:7]([C:9]([OH:11])=[O:10])[C:6]1([CH3:13])[CH3:12])([CH3:4])[CH3:3].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[CH3:3][C:2]1([CH3:4])[C@H:5]2[CH2:8][C@H:7]([C:6]2([CH3:13])[CH3:12])[C:9](=[O:11])[O:10]1
Reactant: CC(C)(O)[C@H]1C[C@@H](C(=O)O)C1(C)C
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: CC1(C)OC(=O)[C@@H]2C[C@H]1C2(C)C
Temperature: 25 °C
Reaction time: 24 h
Yield: 75 %

Procedure:
To a solution of 2.66 g (14.28 mmol) of alcohol 3a in 15 mL of pyridine was added dropwise in 1.40 mL (15.00 mmol) of phosphorus oxychloride at ice-water cooling. The mixture was stirred at room temperature for 24 h, poured onto 75 g of ice, and extracted with ether. The ether extracts were washed with water, 2N hydrochloric acid, then water, saturated aqueous solution of sodium hydrogen carbonate, and brine. After drying over sodium sulfate, the solvent was removed, and the residue was purified by chromatography (30/70, ethyl acetate/hexanes) to afford 1.8 g (10.71 mmol) of pure lactone 4a in 75% yield. Optical purity: 80% ee; [α]24D+5.0 (c 0.1, MeOH); 1H NMR (CDCl3): δ 1.14 (3H, s), 1.37 (3H, s), 1.38 (3H, s), 1.49 (3H, s), 1.81 (1H, d, J=10.59 Hz), 2.10 (1H, dd, J=6.05, 5.67 Hz), 2.48 (1H, ddd, J=10.59, 5.67, 5.30 Hz), 2.63 (1H, dd, J=6.05, 5.30 Hz); 13C NMR (CDCl3): δ 175.04, 82.44, 50.34, 50.01, 40.91, 29.11, 26.11, 25.81, 25.27, 25.25; EI-MS m/z (%): 153 (26), 125 (20), 110 (40), 109 (55), 95 (100), 83 (27), 69 (72), 68 (78), 67 (60), 55 (42), 43 (35), 41 (38); HREIMS: obsd. 153.0911, calcd. for C9H13O2 (M+—CH3): 153.0916.
Reaction SMILES: [C:1]([C:3]1([C:8]2[CH:9]=[CH:10][C:11]([O:16][CH3:17])=[C:12]([CH:15]=2)[CH:13]=O)[CH2:7][CH2:6][CH2:5][CH2:4]1)#[N:2].[ClH:18].Cl.[C:20]1([C@H:26]2[C@@H:31]([NH2:32])[CH2:30][CH2:29][CH2:28][NH:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.Cl.C(C1(C2C=CC(OC)=C(C=2)CN[C@H]2CCCN[C@H]2C2C=CC=CC=2)CC1)#N>>[ClH:18].[ClH:18].[C:1]([C:3]1([C:8]2[CH:9]=[CH:10][C:11]([O:16][CH3:17])=[C:12]([CH:15]=2)[CH2:13][NH:32][C@H:31]2[CH2:30][CH2:29][CH2:28][NH:27][C@H:26]2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:7][CH2:6][CH2:5][CH2:4]1)#[N:2]
Reactant: COc1ccc(C2(C#N)CCCC2)cc1C=O
Reactant: N[C@H]1CCCN[C@H]1c1ccccc1
Agent: COc1ccc(C2(C#N)CC2)cc1CN[C@H]1CCCN[C@H]1c1ccccc1
Agent: Cl
Product: COc1ccc(C2(C#N)CCCC2)cc1CN[C@H]1CCCN[C@H]1c1ccccc1

Procedure:
This compound was prepared from Compound 51 and Compound 3 in the same manner of Compound 5.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][S:27](=[O:30])[CH2:26][CH2:25]2)[C:5]2[N:11]=[CH:10][N:9]=[C:8]([S:12][CH2:13][C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH:17]=[CH:16][CH:15]=3)[C:6]=2[N:7]=1.[NH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>>[C:14]1([CH2:13][S:12][C:8]2[C:6]3[N:7]=[C:2]([N:31]4[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]4)[N:3]=[C:4]([N:24]4[CH2:29][CH2:28][S:27](=[O:30])[CH2:26][CH2:25]4)[C:5]=3[N:11]=[CH:10][N:9]=2)[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: O=S1CCN(c2nc(Cl)nc3c(SCc4cccc5ccccc45)ncnc23)CC1
Reactant: C1CNCCN1
Product: O=S1CCN(c2nc(N3CCNCC3)nc3c(SCc4cccc5ccccc45)ncnc23)CC1

Procedure:
This compound was prepared analogous to Example 1 from 2-chloro-8-(1-naphthylmethyl-thio)-4-(1-oxidothiomorpholino)-pyrimido-[5,4-d]-pyrimidine (m.p.: 212°-215° C.) and piperazine.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([C:30]#[N:31])=[C:11]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C:12]2[N:13]([C:15]([C:18]3[CH:23]=[CH:22][N:21]=[C:20](F)[CH:19]=3)=[CH:16][N:17]=2)[CH:14]=1.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>CS(C)=O.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([C:30]#[N:31])=[C:11]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C:12]2[N:13]([C:15]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([N:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)[CH:19]=3)=[CH:16][N:17]=2)[CH:14]=1
Reactant: CC(C)COc1c(C#N)c(-c2ccc(Cl)cc2Cl)cn2c(-c3ccnc(F)c3)cnc12
Reactant: C1COCCN1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)COc1c(C#N)c(-c2ccc(Cl)cc2Cl)cn2c(-c3ccnc(N4CCOCC4)c3)cnc12
Temperature: 180 °C
Reaction time: 0.5 h

Procedure:
A mixture of 6-(2,4-dichloro-phenyl)-3-(2-fluoro-pyridin-4-yl)-8-isobutoxy-imidazo[1,2-a]pyridine-7-carbonitrile (46.6 mg, 0.10 mmol) and morpholine (0.045 mL, 0.51 mmol) in DMSO (0.8 mL) was heated at 180° C. and stirred for 30 min. The reaction mixture was cooled to RT, diluted in AcOEt (20 mL) and washed with water (2×10 ml). The organic layer was dried over Na2SO4, filtered, and evaporated to dryness to yield the crude 6-(2,4-dichloro-phenyl)-8-isobutoxy-3-(2-morpholin-4-yl-pyridin-4-yl)-imidazo[1,2-a]pyridine-7-carbonitrile intermediate.
Reaction SMILES: [K].[CH3:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:5]([C:6]([OH:8])=[O:7])[C:4]=1[NH2:12].[N+]([C:16]1[C:24](C)=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([OH:20])=[O:19])([O-])=O>[Pd].CO.O>[CH3:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:5]([C:6]([OH:8])=[O:7])[C:4]=1[NH:12][C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([OH:20])=[O:19]
Reactant: Cc1cccc(C(=O)O)c1N
Reactant: Cc1cccc(C(=O)O)c1[N+](=O)[O-]
Agent: [Pd]
Agent: [K]
Solvent: O
Solvent: CO
Product: Cc1cccc(C(=O)O)c1Nc1ccccc1C(=O)O
Temperature: 150 °C
Reaction time: 2 h

Procedure:
The potassium salt of 3-methylanthranilic acid was generated by hydrogenation (Palladium-charcoal catalyst) of a solution of the potassium salt of 2-nitro-3-methylbenzoic acid (37.4 gm) in methanol-H2O (1:4 v/v) with following clarification and evaporation to dryness. To this potassium salt were added 2-chlorobenzoic acid (34.5 gm), K2CO3 (34.5 gm), catalytic Cu powder (0.3 gm), CuBr (0.3 gm), N-methyl-2-pyrrolidone (45 ml) and 2-ethoxyethanol (45 ml) and the mixture was heated in an oil bath at 150° C. with stirring for 21/2 hr. Water (1.5 L) was added to the cooled mixture and the whole warmed until the salts had dissolved and crude product was precipitated from the clarified solution by acidiciation with excess HOAc. The product was washed well with boiling water, then dissolved in 5% aqueous Na2CO3 (500 ml) and decolourising charcoal (5 gm) stirred in. To the boiling clarified solution EtOH (500 ml) was added and the mixture acidified by the slow addition of HOAc. The crystalline diacid which separated from the hot solution was collected, washed with boiling water and dried (48.9 gm). Crystallisation from EtOH--H2O provided homogeneous material as colourless needles of mp 258°-259° C.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:28]=[CH:27][C:16]([CH2:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=2)[C:21](Cl)=[O:22])=[CH:15][CH:14]=1.[OH-].[NH4+:30]>O1CCCC1>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:28]=[CH:27][C:16]([CH2:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=2)[C:21]([NH2:30])=[O:22])=[CH:15][CH:14]=1
Reactant: O=C(Cl)c1cccc(Cc2ccc(OCc3ccc4ccccc4n3)cc2)c1
Reactant: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Product: NC(=O)c1cccc(Cc2ccc(OCc3ccc4ccccc4n3)cc2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-(4-(2-Quinolinylmethyloxy)benzyl)benzoyl chloride (0.05 mol) in tetrahydrofuran (300 ml) is treated with concentrated ammonium hydroxide (25 ml). The reaction mixture is stirred overnight at room temperature andthen evaporated and partitioned between ethyl acetate and water. The ethyl acetate fraction is dried and evaporated to give 3-(4-(2-quinolinylmethyloxy)benzyl)benzamide.
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[CH3:16][C:17]1([CH3:32])[C@@H:19](/[CH:20]=[CH:21]\[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@H:18]1[C:29]([OH:31])=[O:30].[O:33]([C:40]1[N:45]=[C:44]([CH:46](O)[CH3:47])[CH:43]=[CH:42][CH:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:16][C:17]1([CH3:32])[C@@H:19](/[CH:20]=[CH:21]\[C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[C@H:18]1[C:29]([O:31][CH:46]([C:44]1[CH:43]=[CH:42][CH:41]=[C:40]([O:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:45]=1)[CH3:47])=[O:30]
Reactant: CC(C)(C)OC(=O)/C=C\[C@H]1[C@@H](C(=O)O)C1(C)C
Reactant: CC(O)c1cccc(Oc2ccccc2)n1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC(OC(=O)[C@@H]1[C@H](/C=C\C(=O)OC(C)(C)C)C1(C)C)c1cccc(Oc2ccccc2)n1
Temperature: 20 °C
Reaction time: 4 h
Yield: 85.3 %

Procedure:
A solution of 55.7 g of dicyclohexylcarbodiimide, 2.6 g of 4-dimethylamino-pyridine and 450 ml of methylene chloride were added over 25 minutes at 0° C. to a mixture of 65 g of (1R,cis,Z)2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropane-carboxylic acid, 70 g of (RS)1-(6-phenoxy-2-pyridyl)-ethanol and 650 ml of methylene chloride and the mixture was stirred at 20° C. for 4 hours and was vaccum filtered. The filtrate was evaporated to dryness and the residue was chromatographed over silica gel. Elution with and 100-4 n-hexane-ethyl acetate mixture yielded 101 g of (RS)1-(6-phenoxy-2-pyridyl)-ethyl(1R,cis,Z)2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropane-carboxylate with a specific rotation of [α]D20 =+64° (c=1% in toluene).
Reaction SMILES: [CH3:1][N:2]([CH2:22][CH2:23][OH:24])[C:3](=[O:21])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[CH3:25][C:26]([CH3:31])([CH3:30])[C:27](Cl)=[O:28]>>[CH3:1][N:2]([CH2:22][CH2:23][O:24][C:27](=[O:28])[C:26]([CH3:31])([CH3:30])[CH3:25])[C:3](=[O:21])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CC(C)(C)C(=O)Cl
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)N(C)CCO
Product: CCCCCCCC/C=C\CCCCCCCC(=O)N(C)CCOC(=O)C(C)(C)C

Procedure:
N-methyl-N-(2-trimethylacetoxyethyl)oleamide was prepared by the procedure of example 1 from 34 gms. (0.1 mole) of N-methyl-N-(2-hydroxyethyl)oleamide and 12 gms. (0.1 mole) trimethylacetyl chloride. The structure of the final product was characterized on the basis of IR and NMR spectral analyses as described in example 1.
Reaction SMILES: Cl/[CH:2]=[CH:3]/[CH2:4][N:5]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=1)[CH2:6][CH3:7].C(N)CCC.[C:21]([C:25]#[CH:26])([CH3:24])([CH3:23])[CH3:22]>[Cu]I.O1CCCC1>[CH3:22][C:21]([CH3:24])([CH3:23])[C:25]#[C:26]/[CH:2]=[CH:3]/[CH2:4][N:5]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=1)[CH2:6][CH3:7]
Reactant: CCN(C/C=C/Cl)Cc1cccc(O)c1
Reactant: C#CC(C)(C)C
Agent: [Cu]I
Solvent: CCCCN
Solvent: C1CCOC1
Product: CCN(C/C=C/C#CC(C)(C)C)Cc1cccc(O)c1
Temperature: 25 °C
Reaction time: 20 h
Yield: 77 %

Procedure:
To 30 ml of tetrahydrofuran were added 4.51 g (20 mmol) of (E)-N-(3-chloro-2-propenyl)-N-ethyl-3-hydroxybenzylamine, 190.5 mg (1 mmol) of copper (I) iodide and 324 mg (0.28 mmol) of tetrakis (triphenylphosphine)palladium, and further, 3.95 ml (40 mmol) of n butylamine and 2.94 ml (24 mmol) of tert-butylacetylene under ice cooling. The mixture was stirred for 20 hours at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was subjected to silica gel chromatography (n-hexane→n-hexane/ethyl acetate=7/3). The desired fractions were put together and concentrated under reduced pressure to oil. The oil was cooled to crystallize and the crystals were suspended in cooled n-hexane. The crystals were collected by filtration and then dried to obtain 4.20 g (yield: 77%) of the above identified compound as slightly yellow crystalline powder.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=C(C#N)[C:11](=[O:14])[NH:12][CH:13]=1.Cl.[C:18]([OH:21])(=[O:20])[CH3:19]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[C:19]([C:18]([OH:21])=[O:20])[C:11](=[O:14])[NH:12][CH:13]=1
Reactant: N#Cc1cc(-c2ccccc2Cl)c[nH]c1=O
Reactant: CC(=O)O
Agent: Cl
Product: O=C(O)c1cc(-c2ccccc2Cl)c[nH]c1=O

Procedure:
A mixture of 19.0 g. of 5-(2-chlorophenyl)-1,2-dihydro-2-oxo-3-pyridinecarbonitrile and 1:1 concentrated hydrochloric acid and glacial acetic acid is heated at reflux temperature for 16 hours. A yellow solid is separated which is collected by filtration and is washed with water to give 18.4 g. of the product of the Example as yellow needles, m.p. 299°-303° C.
Reaction SMILES: [NH:1]([C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH:23]3[O:25][CH2:24]3)=[CH:17][CH:16]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][NH:27][CH3:28]>CN(C=O)C.CCO>[CH3:26][N:27]([CH2:24][CH:23]([OH:25])[CH2:22][O:21][C:18]1[CH:17]=[CH:16][C:15]([NH:14][C:10]2[N:9]=[C:8]([NH:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:13]=[CH:12][N:11]=2)=[CH:20][CH:19]=1)[CH3:28]
Reactant: CNC
Reactant: c1ccc(Nc2ccnc(Nc3ccc(OCC4CO4)cc3)n2)cc1
Solvent: CCO
Solvent: CN(C)C=O
Product: CN(C)CC(O)COc1ccc(Nc2nccc(Nc3ccccc3)n2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 18 %

Procedure:
4-Anilino-2-(4-(2,3-epoxypropoxy)anilino)pyrimidine (Reference Example I-1, 0.61 g, 1.84 mmol) was dissolved in DMF (2 ml) and treated with dimethylamine (6 mmol, 3 ml of a 2M solution in EtOH). After stirring overnight at ambient temperature the reaction mixture was partitioned between EtOAc and water. The organic phase was washed with water, dried over MgSO4 and evaporated at reduced pressure. The residue was purified by chromatography (0.1%NH3 (aq), 3–10% MeOH in DCM as eluent). Upon evaporation of the fractions, an oily product was obtained,this was triturated with ether to give the title product as a white solid (0.126 g, 18%). NMR (300 MHz): 2.2 (s, 6H), 2.3–2.8 (m, 2H), 3.75–3.95 (m, 3H(, 4.82 (brs, 1H), 6.17 (d, 1H), 6.82 (d, 2H), 6.97 (t, 1H), 7.27 (t, 2H), 7.58 (d, 2H), 7.66 (d, 2H), 7.95 (d, 1H), 8.95 (s, 1H), 9.25 (s, 1H); m/z: (ES+) 380.4 (MH+).
Reaction SMILES: Cl.[NH:2]1[CH2:5][CH:4]([C:6]2[O:10][N:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:29])=[C:15]([NH:17][C:18]([C:20]4[N:24]5[CH:25]=[CH:26][CH:27]=[CH:28][C:23]5=[N:22][CH:21]=4)=[O:19])[CH:16]=3)[N:7]=2)[CH2:3]1.Cl[S:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])(=[O:33])=[O:32]>N1C=CC=CC=1>[N:22]1[CH:21]=[C:20]([C:18]([NH:17][C:15]2[CH:16]=[C:11]([C:8]3[N:7]=[C:6]([CH:4]4[CH2:3][N:2]([S:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:39])([CH3:38])[CH3:40])(=[O:32])=[O:33])[CH2:5]4)[O:10][N:9]=3)[CH:12]=[CH:13][C:14]=2[CH3:29])=[O:19])[N:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=12
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)Cl
Reactant: Cc1ccc(-c2noc(C3CNC3)n2)cc1NC(=O)c1cnc2ccccn12
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccc(-c2noc(C3CN(S(=O)(=O)NC(=O)OC(C)(C)C)C3)n2)cc1NC(=O)c1cnc2ccccn12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirring solution of N-(5-(5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (21) (50 mg, 0.133 mmol) in anhydrous pyridine (1.5 mL) at 0° C. was added tert-butyl chlorosulfonylcarbamate (35 mg, 0.160 mmol). The reaction was stirred to room temperature for 1 hour. The reaction was quenched with water and the solvent was concentrated. The crude product tert-butyl 3-(3-(3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidin-1-ylsulfonylcarbamate (128) was purified by preparative HPLC. 1H NMR (400 MHz, d6-DMSO) δ 11.27 (s, 1H), 10.25 (s, 1H), 9.55-9.53 (m, 1H), 8.76 (s, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.93-7.90 (m, 1H), 7.84 (dd, J=1.6, 8.0 Hz, 1H), 7.75-7.71 (m, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.37-7.34 (m, 1H), 4.37-4.33 (m, 5H), 2.38 (s, 3H), 1.38 (s, 9H). MS m/z 554.17 (M+1)+.
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][CH3:3].[CH2:5]([CH:7]1[O:9][CH2:8]1)[Cl:6]>>[Cl:6][CH2:5][CH:7]([OH:9])[CH2:8][O:4][CH2:1][CH2:2][CH3:3]
Reactant: ClCC1CO1
Reactant: CCCO
Product: CCCOCC(O)CCl
Yield: 73.7 %

Procedure:
A mixture of 300 g 1-propanol (5.0 mol), 231 g epichlorohydrin and 10 g ion exchange resin was refluxed for 22 hours. The reaction mixture was then cooled, filtered and distilled to give 281 g of 1-chloro-3-propoxy-2-propanol (74% yield). Reaction of this product with paraformaldehyde (2.8 mol) gave 202 g of product (69% yield) having the following structure: ##STR23## b.p.: 132° C. at 2 mm Hg.
Reaction SMILES: ClC1C=C(Cl)C=CC=1C1N=C(CC)C(N[C@@H]2C3C(=CC=CC=3)C[C@@H]2O)=NC=1CC.Br[C:31]1[N:32]=[C:33]([CH3:48])[C:34]([NH:38][CH:39]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[CH2:41][CH2:40]2)=[N:35][C:36]=1[CH3:37].[CH3:49][C:50]1[CH:55]=[C:54]([O:56][CH3:57])[CH:53]=[CH:52][C:51]=1B(O)O>>[CH:39]1([NH:38][C:34]2[C:33]([CH3:48])=[N:32][C:31]([C:51]3[CH:52]=[CH:53][C:54]([O:56][CH3:57])=[CH:55][C:50]=3[CH3:49])=[C:36]([CH3:37])[N:35]=2)[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH2:41][CH2:40]1
Reactant: COc1ccc(B(O)O)c(C)c1
Reactant: Cc1nc(NC2CCc3ccccc32)c(C)nc1Br
Agent: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1c2ccccc2C[C@@H]1O
Product: COc1ccc(-c2nc(C)c(NC3CCc4ccccc43)nc2C)c(C)c1

Procedure:
Following the procedure for the preparation of (1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol but substituting 5-bromo-N-(2,3-dihydro-1H-inden-1-yl)-3,6-dimethylpyrazin-2-amine and 2-methyl-4-methoxy phenyl boronic acid, and making non-critical variations provided the title compound as a oil: 1H NMR (CDCl3) δ 1.92, 2.17, 2.26, 2.39, 2.80, 2.98, 3.07, 3.85, 4.54, 5.82, 6.84, 7.15, 7.30, 7.41; MS (ESI+) for C23H25N3O1 m/z 360.4 (M+H)+.