Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([C:11](OCC)=[O:12])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[C:1]([C:5]1[N:10]=[C:9]([CH2:11][OH:12])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)c1cccc(C(C)(C)C)n1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)c1cccc(CO)n1
Temperature: -30 °C
Reaction time: 0.08 h
Yield: 100.5 %

Procedure:
A solution containing the product from Example 115D (1.1 g, 5.3 mmol) in THF (20 mL) at −30° C. was treated with a solution of lithium aluminum hydride (5.3 mL, 1 M in THF), stirred at −30° C. for 5 minutes, treated with water (0.20 mL), 15% NaOH (0.20 mL), and water (0.40 mL) sequentially, stirred for 15 minutes at 25° C., filtered, rinsed with ethyl acetate, and concentrated to give the title compound (0.88 g, quantitative).
Reaction SMILES: [CH3:1][C:2]1[C:10]([O:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][C@H:14]([NH2:18])[CH2:13]2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[Cl:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH:22]=O.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO>[Cl:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH2:22][NH:18][C@H:14]1[CH2:15][CH2:16][CH2:17][C@@H:12]([O:11][C:10]2[C:2]([CH3:1])=[C:3]3[C:7](=[CH:8][CH:9]=2)[NH:6][N:5]=[CH:4]3)[CH2:13]1
Reactant: O=Cc1ccccc1Cl
Reactant: Cc1c(O[C@@H]2CCC[C@H](N)C2)ccc2[nH]ncc12
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Cc1c(O[C@@H]2CCC[C@H](NCc3ccccc3Cl)C2)ccc2[nH]ncc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66.4 %

Procedure:
To a solution of the cis-3-[(4-methyl-1H-indazol-5-yl) oxy]cyclohexanamine (100 mg, 0.407 mmol) obtained in Example 411 in methanol (5 ml) were added 2-chlorobenzaldehyde (46 μl, 0.407 mmol) and acetic acid (23 μl, 0.407 mmol), and the resulting mixture was stirred at room temperature for 30 minutes. Then, acetic acid (46 μl, 0.814 mmol) and sodium cyanoborohydride (28 mg, 0.447 mmol) were added thereto and stirred for 2 hours and a half. Subsequently, the reaction solution was poured into a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=30/1) to obtain cis-N-(2-chlorobenzyl)-3-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanamine (100 mg, 66%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[C:14]([C:22]([O:24][CH3:25])=[O:23])[C:15](=[CH:20][CH:21]=2)[C:16]([O:18][CH3:19])=[O:17])[CH:5]=[CH:6][C:7]=1[OH:8].C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36]>>[CH3:36][C:35]([CH3:38])([CH3:37])[C:34](=[O:39])[CH2:33][O:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[C:14]([C:22]([O:24][CH3:25])=[O:23])[C:15](=[CH:20][CH:21]=2)[C:16]([O:18][CH3:19])=[O:17])=[CH:3][C:2]=1[CH3:1]
Reactant: CC(C)(C)C(=O)CBr
Reactant: COC(=O)c1ccc(CCCc2ccc(O)c(C)c2)cc1C(=O)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COC(=O)c1ccc(CCCc2ccc(OCC(=O)C(C)(C)C)c(C)c2)cc1C(=O)OC

Procedure:
In a manner similar to Example 1g, by reacting 900 mg (2.6 mmol) of dimethyl 4-[3-(3-methyl-4-hydroxyphenyl)propyl]phthalate with 400 mg (2.9 mmol) of potassium carbonate and 390 μl (2.9 mmol) of 1-bromopinacolone. A colorless oil is obtained (m=910 mg; y=79%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([C:17]#[N:18])[C:12](=[CH:15][CH:16]=2)[C:13]#[N:14])=[N:5]1.[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[CH:29]=[C:28]([C:30](O)=[O:31])[NH:27][N:26]=1>>[C:17]([C:11]1[CH:10]=[C:9]([C:6]2[CH:7]=[CH:8][N:4]([CH2:3][CH2:2][NH:1][C:30]([C:28]3[NH:27][N:26]=[C:25]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][N:19]=4)[CH:29]=3)=[O:31])[N:5]=2)[CH:16]=[CH:15][C:12]=1[C:13]#[N:14])#[N:18]
Reactant: O=C(O)c1cc(-c2ccccn2)n[nH]1
Reactant: N#Cc1ccc(-c2ccn(CCN)n2)cc1C#N
Product: N#Cc1ccc(-c2ccn(CCNC(=O)c3cc(-c4ccccn4)n[nH]3)n2)cc1C#N

Procedure:
The title compound was prepared from 4-(1-(2-aminoethyl)-1H-pyrazol-3-yl)phthalonitrile (0.050 g) and 3-(pyridin-2-yl)-1H-pyrazole-5-carboxylic acid (0.042 g) using the method of Example 34(d). Yield 0.062 g. 1H-NMR (400 MHz; d6-DMSO): δ 3.72 (t, 2H), 4.40 (t, 2H), 7.01 (s, 1H), 7.27-7.40 (m, 2H), 7.88-7.94 (m, 3H), 8.14 (d, 1H), 8.32 (d, 1H), 8.35-8.65 (m, 3H), 13.9 (br s, 1H).
Reaction SMILES: Br[C:2]1[NH:3][C:4]2[CH:5]=[CH:6][CH:7]=[C:8]3[C:14](=[O:15])[NH:13][CH2:12][CH2:11][C:10]=1[C:9]=23.C([Sn](CCCC)(CCCC)[C:21]#[C:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)CCC.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>CN(C=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:23]1([C:22]#[C:21][C:2]2[NH:3][C:4]3[CH:5]=[CH:6][CH:7]=[C:8]4[C:14](=[O:15])[NH:13][CH2:12][CH2:11][C:10]=2[C:9]=34)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C1NCCc2c(Br)[nH]c3cccc1c23
Reactant: CCCC[Sn](C#Cc1ccccc1)(CCCC)CCCC
Agent: [Pd]
Agent: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O
Product: O=C1NCCc2c(C#Cc3ccccc3)[nH]c3cccc1c23
Temperature: 60 °C
Yield: 55.2 %

Procedure:
Tricyclic bromide 11 (58.6 mg, 0.22 mmol) in DMF (1 mL) was degassed and treated with tributyl(phenylethynyl)tin (95.2 mg, 0.24 mmol) and tetrakis(triphenylphosphine) palladium(0) (13 mg, 2 mol %). One crystal of 2,6-di-t-butyl-4-methyl phenol was added, and the solution was heated at 60° C. for 10 h. Starting material was still present, so the solution was heated at 100° C. for an additional 2 h. The reaction mixture was cooled to ambient temperature and diluted with water (2 mL) and extracted with EtOAc (5 mL×3). The organic solution was washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product was purified by radial chromatography (2 mm SiO2; 3% MeOH in CH2Cl2) to yield 17 as a white solid (34.8 mg, 55%). mp 255-256° C. (dec); 1H NMR (DMSO-d6) δ 11.86 (s, 1H), 8.17 (m, 1H), 7.75 (d, 1H, J=7.6 Hz), 7.63 (m, 3H), 7.51 (m, 3H), 7.33 (t, 1H, J=7.6 Hz), 3.50 (m, 2H), 3.09 (m, 2H); HRMS (FAB, M+H) Calcd for C19H14N2O+H: 287.1184, Found: 287.1192; Anal. (C19H14N2O.0.6 H2O) C, H, N.
Reaction SMILES: COC([CH:5]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])[C:8]2[CH:18]=[C:19]([Cl:23])[C:20]([Br:22])=[CH:21][C:7]=2[C:6]1=[O:24])=O>CC(O)=O.Cl.O>[CH:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][CH2:5][C:6](=[O:24])[C:7]2[CH:21]=[C:20]([Br:22])[C:19]([Cl:23])=[CH:18][C:8]1=2)=[O:13])([CH3:17])[CH3:16]
Reactant: COC(=O)C1CCN(C(=O)OC(C)C)c2cc(Cl)c(Br)cc2C1=O
Agent: Cl
Solvent: O
Solvent: CC(=O)O
Product: CC(C)OC(=O)N1CCCC(=O)c2cc(Br)c(Cl)cc21
Temperature: 100 °C
Yield: 80.3 %

Procedure:
A mixture of 7-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl ester (1.43 g, 3.42 mmol) in HOAc (30.0 ml), concentrated HCl (9.00 ml) and water (3.00 ml) was heated at 100° C. for 4 hours and then cooled down to room temperature overnight. The solvents were evaporated under reduced pressure, and the residue was partitioned between ethyl acetate (100 ml) and saturated NaHCO3 (aq) (100 ml). The aqueous layer was extracted with more ethyl acetate (20.0 ml). The combined organics washed with brine (3×120 ml), dried over Na2SO4, filtered and concentrated. The material obtained was subjected to the conditions described in step 2 to provide 7-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (0.990 g, 80%) as white solid. MS (ES+): 360, 362 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:3]=1[NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][C:13]=2[O:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23](OC(C)(C)C)=O)[CH2:19][CH2:18]2)[N:8]=[CH:7][N:6]=1.C=O>>[Br:1][C:2]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:3]=1[NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][C:13]=2[O:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)[N:8]=[CH:7][N:6]=1
Reactant: COc1ccc(Br)c(Nc2ncnc3cccc(OCC4CCN(C(=O)OC(C)(C)C)CC4)c23)c1
Agent: C=O
Product: COc1ccc(Br)c(Nc2ncnc3cccc(OCC4CCN(C)CC4)c23)c1

Procedure:
Using an analogous procedure to that described in Example 8, 4-(2-bromo-5-methoxyanilino)-5-[N-(tert-butoxycarbonyl)piperidin-4-ylmethoxy]quinazoline (0.22 g) was reacted with concentrated aqueous formaldehyde solution (0.4 ml) to give the title compound, as a formic acid salt (0.183 g); NMR Spectrum: (CDCl3) 1.7-1.9 (m, 2H), 2.06 (d, 2H), 2.2 (m, 1H), 2.58 (t, 2H), 2.68 (s, 3H), 3.51 (d, 2H), 3.8 (s, 3H), 4.24 (d, 2H), 6.64 (m, 1H), 6.94 (d, 1H), 7.48 (d, 1H), 7.54 (d, 1H), 7.69 (m, 1H), 8.2 (d, 1H), 8.3 (br s, 1H), 8.69 (s, 1H), 9.94 (s, 1H); Mass Spectrum: M+H+ 457 and 459.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18](O)=[O:19])=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:28][CH2:27][C:26]2([C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=[C:29]2[CH3:37])[CH2:25][CH2:24]1)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40]>>[CH2:1]([NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([C:18]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])=[O:19])=[C:13]2[N:12]=[CH:11][C:10]=1[C:21]([N:23]1[CH2:24][CH2:25][C:26]2([C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=[C:29]2[CH3:37])[CH2:27][CH2:28]1)=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC1=Cc2ccccc2C12CCN(C(=O)c1cnc3c(C(=O)O)cnn3c1NCc1ccccc1)CC2
Reactant: CS(N)(=O)=O
Product: CC1=Cc2ccccc2C12CCN(C(=O)c1cnc3c(C(=O)NS(C)(=O)=O)cnn3c1NCc1ccccc1)CC2
Yield: 61 %

Procedure:
In the same manner as in Example 1, step 6 and using 7-benzylamino-6-(2-methylspiro[inden-1,4′-piperidine]-1′-ylcarbonyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.078 g, 0.158 mmol) obtained in step 2 and methanesulfonamide (0.075 g, 0.791 mmol), the title compound (0.055 g, 61%) was obtained.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:24][C@H:25]([CH3:30])[C:26]([OH:29])([CH3:28])[CH3:27])=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:23])(=[N:17]C(OCC)=O)=[O:16])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.CC[O-].[Na+].[Na+].[Cl-]>C(O)C>[Br:1][C:2]1[C:3]([NH:24][C@H:25]([CH3:30])[C:26]([OH:29])([CH3:27])[CH3:28])=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:23])(=[NH:17])=[O:16])=[CH:11][CH:10]=2)=[N:6][CH:7]=1
Reactant: CCOC(=O)N=S(C)(=O)c1ccc(Nc2ncc(Br)c(N[C@H](C)C(C)(C)O)n2)cc1
Agent: CC[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CCO
Product: C[C@@H](Nc1nc(Nc2ccc(S(C)(=N)=O)cc2)ncc1Br)C(C)(C)O

Procedure:
1.65 g (3.30 mmol) of (RS)—S-[4-({5-bromo-4-[(R)-(2-hydroxy-1,2-dimethylpropyl)amino]pyrimidin-2-yl}amino)phenyl]-N-(ethoxycarbonyl)-S-methyl sulfoximide in 6.5 ml of ethanol is mixed with 19.1 ml (6.69 mmol) of a 0.35 molar solution of NaOEt in ethanol and stirred under reflux for 5 hours. The batch is stirred overnight at room temperature and then added to a saturated NaCl solution. It is extracted with ethyl acetate, and the combined organic phases are dried (Na2SO4), filtered and concentrated by evaporation. The remaining residue is purified by chromatography (DCM/EtOH 9:1). 0.95 g (2.22 mmol, corresponding to 67% of theory) of the product is obtained.
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].N1C=CC=CC=1.[Cl:14][CH:15]([O:17][C:18](Cl)=[O:19])[CH3:16].C(OCC)(=O)C>ClCCl>[CH2:1]([O:7][C:18]([O:17][CH:15]([Cl:14])[CH3:16])=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCO
Reactant: CC(Cl)OC(=O)Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CCCCCCOC(=O)OC(C)Cl
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 91 %

Procedure:
A mixture solution of 3.130 g of n-hexanol [Compound (10)] and 2.42 g of pyridine in 30 ml of dry dichloromethane was cooled to -78° C. To this mixture solution was added dropwise a solution of 4.289 g of 1-chloroethylchloroformate in 15 ml of dry dichloromethane for 1 hour. Then, the reaction mixture was stirred for 1.5 hour under ice-cooling and for 15 hours at room temperature. After the reaction, ethyl acetate was added to the reaction mixture. The organic layer was washed with 1N--HCl, saturated sodium bicarbonate aqueous solution and saturated saline solution respectively, and dried over magnesium sulfate. The solvent was removed under reduced pressure and the resulting residue was purified by silica gel column chromatography (hexane: chloroform=3:1) to give 5.697 g (91%) of 1-(n-hexyloxycarbonyloxy)ethyl-chloride [Compound (11)].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]([NH2:18])=[S:17])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.Br[CH:20]1[CH2:25][CH2:24][CH2:23][CH:22]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:21]1=O>C(O)C>[CH2:29]([O:28][C:26]([CH:22]1[C:21]2[N:18]=[C:16]([NH:15][C:5]3[CH:6]=[CH:7][C:8]([N:9]4[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]4)=[C:3]([O:2][CH3:1])[CH:4]=3)[S:17][C:20]=2[CH2:25][CH2:24][CH2:23]1)=[O:27])[CH3:30]
Reactant: COc1cc(NC(N)=S)ccc1-n1cnc(C)c1
Reactant: CCOC(=O)C1CCCC(Br)C1=O
Solvent: CCO
Product: CCOC(=O)C1CCCc2sc(Nc3ccc(-n4cnc(C)c4)c(OC)c3)nc21
Temperature: 25 °C
Yield: 87.3 %

Procedure:
A suspension of [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea (131 mg, 0.50 mmol) and of 2-bromo-6-(carbethoxy)-cyclohexanone (137 mg, 0.55 mmol) in ethanol (5 mL) was stirred at room temperature for 2 days and then heated to reflux under an atmosphere of nitrogen over night. After cooling to room temperature the solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel using dichloromethane/methanol (19:1 v/v) as eluent to yield the title compound (180 mg, 87%) as a white solid. MS ISP (m/e): 413.3 (100) [(M+H)+]. 1H NMR (DMSO-D6, 300 MHz): δ (ppm)=10.28 (s, 1H), 7.66 (d, 1H), 7.64 (s, 1H), 7.21 (d, 1H), 7.11 (d, 1H), 7.01 (s, 1H), 4.10 (q, 2H), 3.76 (s, 3H), 3.66 (m, 1H), 2.62 (m, 2H), 2.14 (s, 3H), 1.68-2.09 (m, 4H), 1.19 (t, 3H).
Reaction SMILES: [OH:1][C@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@@H:3]1[OH:4].O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O.O[C@H]1O[C@H]([C@@H](CO)O)[C@H](O)[C@@H]1O.O[C@@H]1O[C@H]([C@@H](CO)O)[C@H](O)[C@@H]1O.O=C[C@@H]([C@@H]([C@H]([C@H](CO)O)O)O)O.O[C@@H]1O[C@@H](CO)[C@H](O)[C@@H](O)[C@H]1O.O[C@H]1O[C@@H](CO)[C@H](O)[C@@H](O)[C@H]1O.O[C@@H]1O[C@@H]([C@H](CO)O)[C@@H](O)[C@H]1O.O[C@H]1O[C@@H]([C@H](CO)O)[C@@H](O)[C@H]1O>>[O:1]=[CH:2][C@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4]
Reactant: OC[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O
Agent: O=C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO
Agent: OC[C@@H](O)[C@H]1O[C@@H](O)[C@@H](O)[C@H]1O
Agent: OC[C@@H](O)[C@H]1O[C@H](O)[C@@H](O)[C@H]1O
Product: O=C[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
α-D-mannopyranose; β-D-mannopyranose; α-D-mannofuranose; β-D-mannofuranose; L-mannose; α-L-mannopyranose; β-L-mannopyranose; α-L-mannofuranose; β-L-mannofuranose
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([O:26]C(C)C)=[C:22]([F:30])[CH:21]=2)[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[C:4]([CH3:31])[CH:3]=1.B(Cl)(Cl)Cl.O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([F:30])[CH:21]=2)[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[C:4]([CH3:31])[CH:3]=1
Reactant: Cc1cc(Cl)ccc1C(CC(=O)c1ccc(=O)n(C)c1)c1ccc(OC(C)C)c(F)c1
Agent: ClB(Cl)Cl
Solvent: ClCCl
Solvent: O
Product: Cc1cc(Cl)ccc1C(CC(=O)c1ccc(=O)n(C)c1)c1ccc(O)c(F)c1
Temperature: -10 °C
Reaction time: 1 h

Procedure:
A solution of 5-[3-(4-Chloro-2-methyl-phenyl)-3-(3-fluoro-4-isopropoxy-phenyl)-propionyl]-1-methyl-1H-pyridin-2-one (example 323, step 4, 1.969 g) in dichloromethane (32.5 mL) was cooled to −10° C. At this temperature boron trichloride solution (1 M in dichloromethane, 13.4 mL) was slowly added. The reaction mixture was stirred at −10° C. for 1 h. The crude reaction mixture was poured into water/sat. sodium hydrogencarbonate-solution, extracted 3× with ethyl acetate, the organic layers were washed 2× with water, dried over magnesium sulfate and concentrated in vacuo to give the title compound as a light yellow solid, MS (ESI−): m/z=397.9 [M−H]−.
Reaction SMILES: [Br:1]Br.[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C:11](=[O:13])[CH3:12])[CH:8]=[CH:9][CH:10]=1>C(OCC)C>[Br:1][CH2:12][C:11]([C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH3:3])[CH:6]=1)=[O:13]
Reactant: COc1cccc(C(C)=O)c1
Reactant: BrBr
Solvent: CCOCC
Product: COc1cccc(C(=O)CBr)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Bromine (5.32 g, 33.3 mmol) was slowly added dropwise to a solution of 1-(3-methoxyphenyl)ethanone (5.00 g, 33.3 mmol) in diethyl ether (100 ml), and the mixture was stirred at room temperature for 4 hours. The reaction mixture was distilled off under reduced pressure to give the desired product as an oil quantitatively.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[CH3:27])[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[CH:4][CH:3]=1.[CH:28]1([S:31](Cl)(=[O:33])=[O:32])[CH2:30][CH2:29]1>N1C=CC=CC=1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([CH:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][S:31]([CH:28]3[CH2:30][CH2:29]3)(=[O:33])=[O:32])=[CH:3][CH:4]=2)[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[C:21]([CH3:27])[CH:22]=1
Reactant: O=S(=O)(Cl)C1CC1
Reactant: Cc1cc(Cl)ccc1C(CC(=O)c1ccc(=O)n(C)c1)c1ccc(N)cc1
Solvent: c1ccncc1
Product: Cc1cc(Cl)ccc1C(CC(=O)c1ccc(=O)n(C)c1)c1ccc(NS(=O)(=O)C2CC2)cc1

Procedure:
In analogy to example 353, step 2, 5-[3-(4-amino-phenyl)-3-(4-chloro-2-methyl-phenyl)-propionyl]-1-methyl-1H-pyridin-2-one (example 353, step 1) was reacted with cyclopropane-sulfonyl chloride in pyridine to give the title compound as an off-white solid, MS (ESI+): m/z=485.2 [M+H]+.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:21])=[C:11]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:12]=3[CH3:14])[C:7](=[O:22])[C:6]([C:23]([O:25]CC)=[O:24])=[CH:5]2)[CH2:3][CH2:2]1.[OH-].[Na+].Cl>>[O:18]1[CH2:19][CH2:20][N:15]([C:11]2[C:12]([CH3:14])=[C:13]3[C:8]([C:7](=[O:22])[C:6]([C:23]([OH:25])=[O:24])=[CH:5][N:4]3[CH:1]3[CH2:2][CH2:3]3)=[CH:9][C:10]=2[F:21])[CH2:16][CH2:17]1
Reactant: CCOC(=O)c1cn(C2CC2)c2c(C)c(N3CCOCC3)c(F)cc2c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cc1c(N2CCOCC2)c(F)cc2c(=O)c(C(=O)O)cn(C3CC3)c12
Yield: 40.3 %

Procedure:
To ethyl 1-cyclopropyl-7-morpholino-6-fluoro-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylate (0.67 g) is added 10% aqueous sodium hydroxide (7 ml), and the mixture is refluxed for 5 hours. After cooling, the mixture is acidified with diluted hydrochloric acid and is extracted with dichloromethane. The aqueous layer is adjusted to about pH 7.5 with sodium hydrogen carbonate, and the resulting precipitates are recrystallized from ethanol to give 7-morpholino-1-cyclopropyl-6-fluoro-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (0.25 g), as pale yellow flakes, m.p. 227.5°-228° C.
Reaction SMILES: O[CH2:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])O)[OH:4]>O>[CH2:11]1[O:12][C@@H:5]2[C@@H:3]([OH:4])[CH2:2][O:8][C@@H:7]2[C@@H:9]1[OH:10]
Reactant: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Solvent: O
Product: O[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2O
Temperature: 280 °C
Yield: 42.4 %

Procedure:
Sorbitol (25.21 g) was dissolved in water (500 ml) and then transferred to a 1 L autoclave reactor vessel. The catalyst, MFI-40 (HZSM-5 zeolite, 5.02 g), was added. After flushing three times with hydrogen, pressure was set to 300 psi and the reactor was heated with stirring to 280° C. The pressure increased to 1100 psi with heating. Timing began when the reactor reached 280° C. After 30 minutes a 42.4% yield of isosorbide (calculated as mol isosorbide produced/mol starting sorbitol) was obtained.
Reaction SMILES: [C:1]([OH:4])(=[O:3])[CH3:2].[C:5]([OH:8])(=[O:7])[CH3:6].O[C@H:10]1[CH2:27][CH2:26][C@@:25]2([CH2:28]O)[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][CH2:18][C:19]2=[O:30])[CH2:11]1.[H-].C(O[Al](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>O1CCCC1>[C:1]([O:4][C@H:10]1[CH2:27][CH2:26][C@@:25]2([CH2:28][O:7][C:5](=[O:8])[CH3:6])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][CH2:18][C@@H:19]2[OH:30])[CH2:11]1)(=[O:3])[CH3:2]
Reactant: C[C@]12CC[C@H]3[C@@H](CC[C@H]4C[C@@H](O)CC[C@@]43CO)[C@@H]1CCC2=O
Reactant: CC(=O)O
Agent: CC(C)(C)O[Al](OC(C)(C)C)OC(C)(C)C
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [H-]
Solvent: C1CCOC1
Product: CC(=O)OC[C@]12CC[C@H](OC(C)=O)C[C@@H]1CC[C@H]1[C@@H]3CC[C@H](O)[C@@]3(C)CC[C@@H]12

Procedure:
A tetrahydrofuran solution of 3β,19-dihydroxy-5α-androstan-17-one diacetate is added to lithium tri-t-butoxyaluminum hydride in tetrahydrofuran and the resultant solution stirred overnight at room temperature. Aqueous sodium potassium tartrate is added with stirring until a readily filterable precipitate forms. The filtrate is concentrated under reduced pressure and diluted with ether. The resulting solution is washed with water, dried over magnesium sulfate and the ether removed under vacuum. The residual 5α-androstane-3β,17β,19-triol 3,19-diacetate is crystallized from an acetone-hexane solution.
Reaction SMILES: C([N:3]([C:8]([N:10]1[CH2:15][CH2:14][N:13]2[C:16](=[O:31])[O:17][C:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]2[CH2:11]1)=[O:9])[CH2:4][C:5]([OH:7])=[O:6])C.[OH-].[Na+]>C(O)C.O1CCCC1>[O:31]=[C:16]1[N:13]2[CH2:14][CH2:15][N:10]([C:8]([NH:3][CH2:4][C:5]([OH:7])=[O:6])=[O:9])[CH2:11][CH:12]2[C:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:17]1
Reactant: CCN(CC(=O)O)C(=O)N1CCN2C(=O)OC(c3ccccc3)(c3ccccc3)C2C1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(O)CNC(=O)N1CCN2C(=O)OC(c3ccccc3)(c3ccccc3)C2C1
Temperature: 0 °C
Reaction time: 3 h
Yield: 84.3 %

Procedure:
Ethyl N-[(tetrahydro-3-oxo-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazin-7(1H)-yl)carbonyl]glycine (1.5 g, 3.6 mmol) was dissolved in ethanol (10 mL) and tetrahydrofuran (2 mL). With ice cooling, a 4 M aqueous sodium hydroxide solution (1.0 mL, 4.0 mmol) was added thereto, and the mixture was stirred at 0° C. for 3 hours. The reaction solution was concentrated under reduced pressure, and diethyl ether and water were added to the residue. The aqueous layer was neutralized with 4 M hydrochloric acid, which was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and hexane was added to the residue. The resulting mixture was powdered and dried to obtain the title compound (1.2 g, yield 84%).
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([C:12]([NH2:14])=[O:13])[O:7][C:8]=1[CH:9]([CH3:11])[CH3:10])([CH3:3])[CH3:2].Br[C:16]1[O:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:18][CH:17]=1>>[CH:1]([C:4]1[CH:5]=[C:6]([C:12]([NH:14][C:16]2[O:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:18][CH:17]=2)=[O:13])[O:7][C:8]=1[CH:9]([CH3:10])[CH3:11])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccc(Br)o1
Reactant: CC(C)c1cc(C(N)=O)oc1C(C)C
Product: COC(=O)c1ccc(NC(=O)c2cc(C(C)C)c(C(C)C)o2)o1
Yield: 48.9 %

Procedure:
4,5-Diisopropylfuran-2-carboxamide (55 mg, 0.282 mmol) and methyl 5-bromofuran-2-carboxylate (116 mg, 0.566 mmol) were coupled. The reaction mixture was treated in a conventional manner, and the resultant was purified by silica gel chromatography [hexane-ethyl acetate (9:1)] and recrystallized to obtain methyl 5-[(4,5-diisopropylfuran-2-carbonyl)amino]-2-furancarboxylate (44 mg, 49%) and the collected starting material (26 mg, 47%) as colorless needles.