Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:16]3[N:15]=2)[C:5](=[O:8])[NH:6][CH:7]=1.[H-].[Li+].Br[CH2:31][CH2:32][CH2:33][N:34]1[C:42](=[O:43])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]1=[O:44]>CN(C=O)C>[O:44]=[C:35]1[C:36]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:42](=[O:43])[N:34]1[CH2:33][CH2:32][CH2:31][N:6]1[CH:7]=[C:2]([F:1])[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:16]3[N:15]=2)[C:5]1=[O:8]
Reactant: CCOC(=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)c[nH]c3=O)nc12
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Agent: [H-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)cn(CCCN4C(=O)c5ccccc5C4=O)c3=O)nc12
Temperature: 25 °C
Yield: 66.3 %

Procedure:
To a DMF (5 mL) suspension of (R)-ethyl 5-(2-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (0.20 g, 0.54 mmol) was added LiH (6.8 mg, 0.81 mmol) at 0° C., followed first by 20-minute stirring, then addition of a DMF (1 mL) solution of 2-(3-bromopropyl)isoindoline-1,3-dione (0.29 g, 1.1 mmol). The reaction was warmed to ambient temperature and stirred for 17 hours. After cooling to 0° C. the reaction was quenched with ice-water (30 mL) and the aqueous was extracted with EtOAc (3×50 mL). The combined organic layers were backwashed with water and brine, dried (MgSO4), filtered, and concentrated. The crude material was purified by silica column chromatography, eluting with 2% MeOH/DCM to yield the desired product (0.2 g, 66% yield). MS (apci) m/z=559.0 (M+H).
Reaction SMILES: Br[C:2]1[C:10]([F:11])=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:12])[N:7]=2)[C:3]=1[C:13]([O:15][CH3:16])=[O:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[C:42]([O:46][CH3:47])(=[O:45])[CH:43]=[CH2:44]>CN(C)C=O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:11][C:10]1[C:2](/[CH:44]=[CH:43]/[C:42]([O:46][CH3:47])=[O:45])=[C:3]([C:13]([O:15][CH3:16])=[O:14])[C:4]2[C:8]([CH:9]=1)=[N:7][N:6]([CH3:12])[CH:5]=2
Reactant: COC(=O)c1c(Br)c(F)cc2nn(C)cc12
Reactant: C=CC(=O)OC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)/C=C/c1c(F)cc2nn(C)cc2c1C(=O)OC
Temperature: 100 °C
Yield: 88.4 %

Procedure:
A suspension of methyl 5-bromo-6-fluoro-2-methyl-2H-indazole-4-carboxylate (503 mg, 1.75 mmol), palladium acetate (39.3 mg, 0.175 mmol), triphenylphosphine (91.8 mg, 0.350 mmol), potassium carbonate (266 mg, 1.93 mmol) and methyl acrylate (314 μL, 3.50 mmol) in N,N-dimethylformamide (8.8 mL) was stirred with heating at 100° C. for 1 hr. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→60/40) to give the title compound (452 mg, yield 88%).
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:12])[C:9]([CH3:11])=[CH2:10].[OH:14][CH:15]1[C:25]2=[C:26]3[C:21](=[CH:22][CH:23]=[CH:24]2)[CH:20]=[CH:19][CH:18]=[C:17]3[CH2:16]1>C1(C)C=CC=CC=1>[C:8]([O:14][CH:15]1[C:25]2=[C:26]3[C:21](=[CH:22][CH:23]=[CH:24]2)[CH:20]=[CH:19][CH:18]=[C:17]3[CH2:16]1)(=[O:12])[C:9]([CH3:11])=[CH2:10]
Reactant: OC1Cc2cccc3cccc1c23
Reactant: C=C(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: C=C(C)C(=O)OC1Cc2cccc3cccc1c23

Procedure:
With stirring and ice cooling, 111 g of triethylamine was added to a mixture of 120 g of methacrylic acid chloride, 170 g of 1-hydroxyacenaphthene, and 1500 g of toluene. The mixture was stirred at room temperature for 16 hours. By standard aqueous work-up and solvent distillation, a crude product was obtained. It was purified by column chromatography, yielding the target compound, acenaphthenyl methacrylate.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:11].C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[CH2:18]([O:11][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=1[NH2:1])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: BrCc1ccccc1
Reactant: Nc1c(O)cccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1c(OCc2ccccc2)cccc1[N+](=O)[O-]
Reaction time: 1.5 h

Procedure:
6.16 g (40 mM) of 2-amino-3-nitrophenol, 60 ml of dimethylformamide and 6.62 g (48 mM) of dipotassium carbonate are introduced into a round-bottomed flask. 4.75 ml (40 mM) of benzyl bromide are then added dropwise and the reaction mixture is brought to 80° C. After havingbeen stirred under an inert atmosphere for 1.5 hours, the mixture is pouredinto ice-cold water and then extracted with 200 ml of ethyl acetate. The organic phase is separated by settling and, after washing with a saturatedsodium chloride solution, it is dried over magnesium sulphate and evaporated to dryness. The product is chromatographed on a silica column (eluent: 10% ethyl acetate and 90% hexane) to lead to 8.8 g (90%) of the expected compound in the form of an orangey oil.
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][C:7]2[C:8](=[O:19])[O:9][C:10]3[C:15]([C:16]=2[CH3:17])=[CH:14][CH:13]=[C:12]([OH:18])[CH:11]=3)=[CH:4][CH:3]=1.[N:22]1([C:28](Cl)=[O:29])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[C:8](=[O:19])[O:9][C:10]3[C:15]([C:16]=2[CH3:17])=[CH:14][CH:13]=[C:12]([O:18][C:28]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[O:29])[CH:11]=3)=[CH:20][CH:21]=1
Reactant: O=C(Cl)N1CCOCC1
Reactant: Cc1c(Cc2ccc(F)cc2)c(=O)oc2cc(O)ccc12
Product: Cc1c(Cc2ccc(F)cc2)c(=O)oc2cc(OC(=O)N3CCOCC3)ccc12

Procedure:
The title compound was prepared from 3-(4-fluorobenzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and morpholine-4-carbonyl chloride. The crude product was recrystallized (ethanol) (78%, crystals). HPLC-MS m/z=398.0 (M+1), Rt: 4.3 min.
Reaction SMILES: [C:1]([C:3]1[C:8]([CH3:9])=[CH:7][C:6]([C:10]2[CH2:11][CH2:12][N:13]([C:16]([C@@H:18]3[C@@H:23]([C:24]([O:26][CH3:27])=[O:25])[CH2:22][C@@H:21]([OH:28])[CH2:20][N:19]3[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:17])[CH2:14][CH:15]=2)=[CH:5][C:4]=1[CH3:36])#[N:2].O1CCCC1.[Cl:42][C:43]1[CH:44]=[C:45](O)[CH:46]=[N:47][CH:48]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>>[Cl:42][C:43]1[CH:44]=[C:45]([O:28][C@@H:21]2[CH2:20][N:19]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[C@H:18]([C:16]([N:13]3[CH2:12][CH:11]=[C:10]([C:6]4[CH:7]=[C:8]([CH3:9])[C:3]([C:1]#[N:2])=[C:4]([CH3:36])[CH:5]=4)[CH2:15][CH2:14]3)=[O:17])[C@@H:23]([C:24]([O:26][CH3:27])=[O:25])[CH2:22]2)[CH:46]=[N:47][CH:48]=1
Reactant: Oc1cncc(Cl)c1
Reactant: COC(=O)[C@H]1C[C@@H](O)CN(C(=O)OC(C)(C)C)[C@@H]1C(=O)N1CC=C(c2cc(C)c(C#N)c(C)c2)CC1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)[C@H]1C[C@H](Oc2cncc(Cl)c2)CN(C(=O)OC(C)(C)C)[C@@H]1C(=O)N1CC=C(c2cc(C)c(C#N)c(C)c2)CC1
Temperature: 70 °C
Yield: 36.9 %

Procedure:
To a solution of 1-tert-butyl 3-methyl(2S,3S,5R)-2-[4-(4-cyano-3,5-dimethylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl-5-hydroxypiperidine-1,3-dicarboxylate (100 mg, 0.0002 mol) in tetrahydrofuran (0.912 mL, 0.0112 mol) was added 5-chloropyridin-3-ol (35.0 mg, 0.000270 mol), triphenylphosphine (70.8 mg, 0.000270 mol), followed by diisopropyl azodicarboxylate (0.0532 mL, 0.000270 mol). The mixture was heated at 70 Celsius overnight. After concentrated to dry, the mixture was purified on silica gel, elution with 0 to 40% EtOAc in hexane, to yield the desired product (45 mg, 32.84%). MS (ESI) (M+H) 609.1.
Reaction SMILES: O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:13]([C:17]1[CH2:24][S:23][CH:22]2[N:19]([C:20](=[O:33])[CH:21]2[NH:25]C(OC(C)(C)C)=O)[C:18]=1[C:34]([O:36][CH:37]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35])[C:14]([CH3:16])=[O:15]>C(#N)C>[CH2:13]([C:17]1[CH2:24][S:23][CH:22]2[N:19]([C:20](=[O:33])[CH:21]2[NH2:25])[C:18]=1[C:34]([O:36][CH:37]([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:35])[C:14]([CH3:16])=[O:15]
Reactant: CC(=O)CC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)OC(C)(C)C)C2SC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CC#N
Product: CC(=O)CC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(N)C2SC1
Reaction time: 0.5 h

Procedure:
A solution of p-toluenesulphonic acid monohydrate (3.8 g) in acetonitrile (50 cc) is added, in the course of 30 minutes, to a solution of 3-acetonyl-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (5.23 g) in acetonitrile (50 cc) at 40° C. The mixture is kept at 40° C. for 30 minutes and then concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. to a volume of about 30 cc. It is diluted with methylene chloride (150 cc) and the solution is washed with a saturated aqueous solution of sodium bicarbonate (50 cc) and dried over magnesium sulphate. This yields a solution of 3-acetonyl-7-amino-2-benzhydryloxycarbonyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene, which is identical to the product described in Reference Example 2.
Reaction SMILES: [NH:1]([C:3]1[NH:7][C:6]2[CH:8]=[CH:9][C:10]([CH3:12])=[CH:11][C:5]=2[N:4]=1)[NH2:2].[C:13]([CH:16]([CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1)[C:17](OCC)=[O:18])(=O)[CH3:14]>>[CH3:14][C:13]1[C:16]([CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=2)=[C:17]([OH:18])[N:1]([C:3]2[NH:7][C:6]3[CH:8]=[CH:9][C:10]([CH3:12])=[CH:11][C:5]=3[N:4]=2)[N:2]=1
Reactant: Cc1ccc2[nH]c(NN)nc2c1
Reactant: CCOC(=O)C(Cc1ccc2ccccc2c1)C(C)=O
Product: Cc1ccc2[nH]c(-n3nc(C)c(Cc4ccc5ccccc5c4)c3O)nc2c1

Procedure:
Using 2-hydrazino-5-methyl-1H-benzimidazole (4) obtained in Example 1, step 3 and ethyl 2-acetyl-3-(2-naphthyl)propanoate (39), and by a method similar to that in Example 1, step 4, 3-methyl-1-(5-methyl-1H-benzimidazol-2-yl)-4-(2-naphthylmethyl)-1H-pyrazol-5-ol (40) was obtained.
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9]([NH:11][CH2:12][C@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2CNC(=O)OC(C)(C)C)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(C(F)(F)F)=O>ClCCl>[NH:14]1[CH2:15][CH2:16][CH2:17][C@@H:13]1[CH2:12][NH:11][C:9](=[O:10])[O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(C)OC(=O)NCN1CCC[C@@H]1CNC(=O)OCc1ccccc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(NC[C@H]1CCCN1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 74.2 %

Procedure:
To a solution of 1,1-dimethylethyl (2R)-2-[({[(phenylmethyl)oxy]carbonyl}amino)methyl]-1-pyrrolidinylmethylcarbamate (D108, 2.07 g, 6.1 mmol) in 16 ml of dichloromethane, cooled to 0° C., were added 4 ml of TFA. The reaction mixture was allowed to warm-up to r.t. and then it was stirred at this temperature for 30 mins. The title compound (1.06 g, y=88%) was isolated after purification by SCX. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.00-7.66 (m, 5 H) 4.90-5.20 (m, 2 H) 3.12-3.24 (m, 1 H) 2.97-3.09 (m, 1 H) 2.84-2.97 (m, 2 H) 2.61-2.82 (m, 2 H) 1.44-1.83 (m, 3 H) 1.14-1.40 (m, 1 H)
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH:11]=O)[CH:4]=[CH:3][CH:2]=1.N1(C2C=C[C:21]([CH:22]=[O:23])=CC=2)C=CC=N1>>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH:11]=[CH:21][CH:22]=[O:23])[CH:4]=[CH:3][CH:2]=1
Reactant: O=Cc1cccc2cccnc12
Reactant: O=Cc1ccc(-n2cccn2)cc1
Product: O=CC=Cc1cccc2cccnc12

Procedure:
The title compound was prepared by a procedure analogous to Reference Example 30 by substituting 8-quinolinecarboxaldehyde (prepared as described in J. Am. Chem. Soc. 1997, 119, 8891) for the 4-(1H-pyrazol-1-yl)-benzaldehyde of Reference Example 30. MS 184 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4](/[CH:10]=[C:11](\[C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)/[C:12]#[N:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].C([NH:33][C@H:34]([C:39]([NH2:41])=[O:40])[CH2:35][CH2:36][CH2:37][NH2:38])(OC(C)(C)C)=O.[ClH:42].O1CCOCC1.C(OCC)C>ClCCl>[NH2:1][C:2]1[CH:3]=[C:4](/[CH:10]=[C:11](\[C:14]2[CH:15]=[C:16]([O:24][CH3:25])[C:17]([O:22][CH3:23])=[C:18]([O:20][CH3:21])[CH:19]=2)/[C:12]#[N:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[ClH:42].[NH2:33][C@H:34]([C:39]([NH2:41])=[O:40])[CH2:35][CH2:36][CH2:37][NH2:38]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCN)C(N)=O
Agent: COc1ccc(/C=C(/C#N)c2cc(OC)c(OC)c(OC)c2)cc1N
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOCC
Solvent: ClCCl
Product: NCCC[C@H](N)C(N)=O

Procedure:
(E)-3-(3Amino-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-prop-2-enenitrile-Boc-L-ornithineamide (730 mg, 1.11 mmols) was dissolved in 5 ml of dichloromethane, and 5 ml of a solution of 4-M hydrochloric acid and dioxane were added thereto. The mixture was reacted at room temperature for 1 hour. One-hundred milliliters of diethyl ether were added thereto, and the resulting mixture was filtered. The thus-obtained powder was recrystallized from a mixture of methanol and ethyl acetate at a ratio by volume of 1:1 to produce 286 mg (0.542 mmols) of the final compound in a yield of 48%.
Reaction SMILES: [C:1]([C@:3]1([OH:24])[CH:9]=[CH:8][C@H:7]2[C@H:10]3[C@H:19]([CH2:20][CH2:21][C@:4]12[CH2:5][CH3:6])[C@@H:18]1[C:13](=[CH:14][C:15](=[O:23])[CH2:16][C@@H:17]1[OH:22])[CH2:12][CH2:11]3)#[CH:2].[C:25](OC(=O)C)(=[O:27])[CH3:26]>N1C=CC=CC=1>[C:25]([O:22][C@@H:17]1[C@H:18]2[C:13]([CH2:12][CH2:11][C@@H:10]3[C@@H:19]2[CH2:20][CH2:21][C@@:4]2([CH2:5][CH3:6])[C@H:7]3[CH:8]=[CH:9][C@:3]2([C:1]#[CH:2])[OH:24])=[CH:14][C:15](=[O:23])[CH2:16]1)(=[O:27])[CH3:26]
Reactant: CC(=O)OC(C)=O
Reactant: C#C[C@]1(O)C=C[C@H]2[C@@H]3CCC4=CC(=O)C[C@H](O)[C@@H]4[C@H]3CC[C@@]21CC
Solvent: c1ccncc1
Product: C#C[C@]1(O)C=C[C@H]2[C@@H]3CCC4=CC(=O)C[C@H](OC(C)=O)[C@@H]4[C@H]3CC[C@@]21CC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
200 mg of 17α-ethynyl-1α,17-dihydroxy-18-methyl-4,15-estradien-3-one is dissolved in 10 ml of pyridine and combined under ice-cooling dropwise with 3 m of acetic anhydride. The solution is then allowed to warm up and agitated at room temperature overnight. Thereafter the reaction mixture is stirred into ice water, the precipitated, oily-crystalline product is vacuum-filtered, taken up in ethyl acetate, washed neutral, dried over Na2SO4, and concentrated to dryness under vacuum. The remaining residue is crystallized from ether/hexane, thus obtaining 165 mg of 1α-acetoxy-17α-ethynyl-17-hydroxy-18-methyl-4,15-estradien-3-one, mp 123°-126° C.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[NH:4][N:3]=1.Cl[C:12]([O:14][CH2:15][CH:16]=[CH2:17])=[O:13]>O1CCOCC1>[C:7]([C:5]1[NH:4][N:3]=[C:2]([NH:1][C:12](=[O:13])[O:14][CH2:15][CH:16]=[CH2:17])[CH:6]=1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)c1cc(N)n[nH]1
Reactant: C=CCOC(=O)Cl
Solvent: C1COCCO1
Product: C=CCOC(=O)Nc1cc(C(C)(C)C)[nH]n1
Yield: 43.7 %

Procedure:
5.5 g of Compound [II] was dissolved in 30 ml of dioxane, and 4.2 g of allyl chloroformate was added to the solution. The mixture was allowed to react for 8 hours under refluxing. After completion of the reaction, the solvent was distilled off, and hexane and a potassium carbonate aqueous solution were added to the residue to form crystals. Thus, 3.4 g of allyl N-(5-t-butyl-3-pyrazolyl)carbamate was obtained. This compound was recrystallized from hydrous methanol and found to have a melting point of 131° C. to 132° C.
Reaction SMILES: [F:1][C:2]1[C:3](F)=[C:4]2[O:9][CH2:8][CH:7]([CH3:10])[N:6]3[CH:11]=[C:12]([C:17]([OH:19])=[O:18])[C:13](=[O:16])[C:14]([CH:15]=1)=[C:5]23.[NH:21]1[CH2:25][CH2:24][CH:23]([CH2:26][NH2:27])[CH2:22]1>C(#N)C>[NH2:27][CH2:26][CH:23]1[CH2:24][CH2:25][N:21]([C:3]2[C:2]([F:1])=[CH:15][C:14]3[C:13](=[O:16])[C:12]([C:17]([OH:19])=[O:18])=[CH:11][N:6]4[CH:7]([CH3:10])[CH2:8][O:9][C:4]=2[C:5]=34)[CH2:22]1
Reactant: CC1COc2c(F)c(F)cc3c(=O)c(C(=O)O)cn1c23
Reactant: NCC1CCNC1
Solvent: CC#N
Product: CC1COc2c(N3CCC(CN)C3)c(F)cc3c(=O)c(C(=O)O)cn1c23
Yield: 922.4 %

Procedure:
0.75 g (0.27 mmole) of 9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, 40 ml acetonitrile, and 0.80 g (8.0 mmole) of 3-pyrrolidinemethanamine were refluxed overnight. The solvent was removed at reduced pressure and the residue titurated with 40 ml of ethanol/ether (1:1), to give 0.90 g of 10-[3-(aminomethyl)-1-pyrrolidinyl]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, mp 213°-216° C.
Reaction SMILES: N(C(C)=O)(CNC(C)=O)CNC(C)=O.C=O.O.[C:18]([OH:21])(=[O:20])[CH3:19].N(CC(O)=O)CC(O)=O.[C:31]([NH:34][CH2:35][C:36]([OH:38])=[O:37])(=[O:33])[CH3:32]>CC(C)=O>[C:31]([N:34]([CH2:35][C:36]([OH:38])=[O:37])[CH2:19][C:18]([OH:21])=[O:20])(=[O:33])[CH3:32]
Reactant: CC(=O)NCC(=O)O
Reactant: CC(=O)O
Agent: C=O
Agent: CC(=O)NCN(CNC(C)=O)C(C)=O
Agent: O=C(O)CNCC(=O)O
Solvent: CC(C)=O
Solvent: O
Product: CC(=O)N(CC(=O)O)CC(=O)O
Temperature: 110 °C
Yield: 95 %

Procedure:
A 300 mL autoclave was charged with acetamide (VII)(11.8 g, 0.2 mole), 95% paraformaldehyde (13.6 g, 0.43 mole), water (12.9 g, 0.72 mole), acetic acid (2.1 g, 0.035 mole), acetone (90 mL) and Co2(CO)8 (2.1 g, 0.006 mol) and pressurized to 3200 psi (22,069 kPa) CO:H2 (95:5) at 25° C. This mixture was heated to 110° C. for 30 min. HPLC analysis of this stream indicated a 95% yield of (XVI), 0.5% (XIV), and 4.5% (XVIII).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[CH:5][C:4]=1[CH:13]=[CH:14]C.BrN1[C:21](=[O:22])CCC1=O>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[CH:5][C:4]=1[CH:13]([CH3:14])[CH:21]=[O:22]
Reactant: CC=Cc1cc(OC)c(OC)cc1OC
Reactant: O=C1CCC(=O)N1Br
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: [Br-]
Solvent: O
Product: COc1cc(OC)c(C(C)C=O)cc1OC
Yield: 43 %

Procedure:
A mixture of 2,4,5 trimethoxy phenyl propene (1 mmol), N-bromosuccinimide (1.2 mmol), water (14 ml), cetyltrimethyl ammonium bromide (0.3 mmol) were taken in a 100 ml round bottom flask fitted with a condenser. The flask was shaken well and placed inside the monomode microwave oven and irradiated (220 W, 200° C.) for 12 minutes in parts. After completion of reaction, the reaction mixture was worked up as in example-1 to provide the corresponding 2-(2,4,5 trimethoxy phenyl)propionaldehyde (43% yield) whose spectral data matched with that mentioned in example-1.
Reaction SMILES: Br[CH2:2][CH:3]=[CH:4][C:5]([OH:7])=[O:6].C([CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[NH:16]C2C(C=1)=CC=CC=2)(O)=O.CC(CCCC(Cl)=O)C(Cl)=O>>[C:5]([C:4]1[NH:16][C:15]2[C:2]([CH:3]=1)=[CH:11][CH:12]=[CH:13][CH:14]=2)([OH:7])=[O:6]
Reactant: O=C(O)C=CCBr
Reactant: O=C(O)CCCCc1cc2ccccc2[nH]1
Agent: CC(CCCC(=O)Cl)C(=O)Cl
Product: O=C(O)c1cc2ccccc2[nH]1

Procedure:
Refer to 32(a) using 4-bromo-2-butenoic acid as the alkylating agent. Preparation of 2-(4-carboxy-n-butyl) indole: Refer to Example 3 using methyl adipyl chloride as the acid chloride. The methyl ester was hydrolyzed in the cyclization workup to provide the product carboxyindole. In the alternative, refer to Example 32b) using 2-(4-carboxy-3-buten-1-yl) indole as the starting material.
Reaction SMILES: [F:1][C:2]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[N:19]=[C:18](Cl)[CH:17]=[C:16]([Cl:21])[N:15]=2)=[CH:9][CH:8]=1)=[O:5].[CH3:27][C:28]1[CH:29]=[C:30]([NH2:33])[NH:31][N:32]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>C(OCC)(=O)C.CN(C)C=O>[F:26][C:22]1[CH:23]=[CH:24][CH:25]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([S:13][C:14]2[N:15]=[C:16]([Cl:21])[CH:17]=[C:18]([NH:33][C:30]3[NH:31][N:32]=[C:28]([CH3:27])[CH:29]=3)[N:19]=2)=[CH:11][CH:12]=1)=[O:5]
Reactant: Cc1cc(N)[nH]n1
Reactant: O=C(Nc1ccc(Sc2nc(Cl)cc(Cl)n2)cc1)c1c(F)cccc1F
Agent: [I-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1cc(Nc2cc(Cl)nc(Sc3ccc(NC(=O)c4c(F)cccc4F)cc3)n2)[nH]n1
Temperature: 90 °C
Reaction time: 18 h
Yield: 99.3 %

Procedure:
A 50 ml round bottom flask was charged with 2,6-difluoro-N-[4-(4,6-dichloro-pyrimidin-2-ylsulfanyl)-phenyl]-benzamide (1.0 g, 2.3 mmol), 5-methyl-2H-pyrazol-3-ylamine (250 mg, 2.58 mmol), sodium iodide (351 mg, 2.34 mmol), diisopropylethyl amine (333 mg, 2.58 mmol) and dimethylformamide (5 ml) under nitrogen. The reaction mixture was stirred at 90° C. for 18 h, then allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate (25 ml), washed with saturated sodium bicarbonate solution and brine. The organic was dried over magnesium sulfate, filtered and concentrated in vacuo. The compound was purified by flash chromatography (75 to 80% ethyl acetate/petrol) to give the title compound (1.08 g, 98%). 1H NMR (DMSO) 2.00 (3H, s), 5.25 (1H, brs), 6.48 (1H, brs), 7.30-7.97 (7H, m), 10.28 (1H, s), 10.89 (1H, s), 11.90 (1H, s); MS(ES+): 473.4.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][OH:4].[C:12](=O)(OCC)[O:13]CC.Cl>C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>[CH2:5]([C@H:2]1[CH2:3][O:4][C:12](=[O:13])[NH:1]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCOC(=O)OCC
Reactant: N[C@H](CO)Cc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: O=C1N[C@@H](Cc2ccccc2)CO1
Reaction time: 3 h
Yield: 100 %

Procedure:
To a mixture of (2S)-2-amino-3-phenyl-1-propanol (0.649 g; 4.29 mmol) and diethyl carbonate (1.04 ml; 8.58 mmol), anhydrous potassium carbonate (20 mg; 0.14 mmol) was added, and the mixture was stirred at 120° to 130° C. for 3 hours. After cooling, to the resulting mixture 1N hydrochloric acid (1.5 ml) and ethyl acetate (about 50 ml) were added and stirred. The organic layer was separated and washed with brine, and dried over anhydrous magnesium sulfate. Distilling off the solvent under reduced pressure gave (4S)-4-benzyloxazolidin-2-one (0.760 g, quantitative yield) as a colorless solid. The sample for analysis was obtained by recrystallization from a mixed solvent of cyclohexane and toluene (1:1). Colorless crystals. M.P., 88°-89° C.
Reaction SMILES: [Li].C([O:4][C:5]([C:7]1[CH:8]=[C:9]2[CH:15]=[CH:14][O:13][C:10]2=[N:11][CH:12]=1)=[O:6])C>>[O:13]1[C:10]2=[N:11][CH:12]=[C:7]([C:5]([OH:6])=[O:4])[CH:8]=[C:9]2[CH:15]=[CH:14]1
Reactant: CCOC(=O)c1cnc2occc2c1
Agent: [Li]
Product: O=C(O)c1cnc2occc2c1

Procedure:
Furo[2,3-b]pyridine-5-carboxylic acid (31 mg) was obtained as a lithium salt from furo[2,3-b]pyridine-5-carboxylic acid ethyl ester described in Preparation Example P-4 (33 mg, 0.17 mmol) according to an analogous method to Example T-2.
Reaction SMILES: [CH3:1][N:2]([CH3:24])[S:3]([CH2:6][CH2:7][N:8]1[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[C:11]([OH:18])=[C:10]([C:19](OC)=[O:20])[C:9]1=[O:23])(=[O:5])=[O:4].[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][NH2:33])=[C:28]([S:34][CH3:35])[CH:27]=1>CCO>[CH3:1][N:2]([CH3:24])[S:3]([CH2:6][CH2:7][N:8]1[C:17]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[C:11]([OH:18])=[C:10]([C:19]([NH:33][CH2:32][C:29]2[CH:30]=[CH:31][C:26]([F:25])=[CH:27][C:28]=2[S:34][CH3:35])=[O:20])[C:9]1=[O:23])(=[O:5])=[O:4]
Reactant: CSc1cc(F)ccc1CN
Reactant: COC(=O)c1c(O)c2ncccc2n(CCS(=O)(=O)N(C)C)c1=O
Solvent: CCO
Product: CSc1cc(F)ccc1CNC(=O)c1c(O)c2ncccc2n(CCS(=O)(=O)N(C)C)c1=O

Procedure:
In a manner similar to that described in Example 2, methyl 1-{2-[(dimethylamino)sulfonyl]ethyl}-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate (0.3 g, 0.84 mmol) was suspended in 8 mL of absolute EtOH and treated with 1-[4-fluoro-2-(methylthio)phenyl]methanamine (0.21 g, 1.3 mmol). The mixture was brought to reflux for 4.5 hours, cooled, and the solids collected and washed with a little cold EtOH to give the product as a white solid.