Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.Br[CH2:11][C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:17][CH:16]=1)=[O:13].BrCC(Br)=O.C(C1C=CC(N)=CC=1)(C)(C)C>>[N:1]1([CH2:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:17][CH:16]=2)=[O:13])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: c1ccc2[nH]cnc2c1
Reactant: CC(C)(C)c1ccc(NC(=O)CBr)cc1
Agent: CC(C)(C)c1ccc(N)cc1
Agent: O=C(Br)CBr
Product: CC(C)(C)c1ccc(NC(=O)Cn2cnc3ccccc32)cc1

Procedure:
The title compound was synthesised according to the procedure described in Example 94 from 1H-benzoimidazole and 2-bromo-N-(4-tert-butyl-phenyl)-acetamide. The latter was synthesized from bromoacetyl bromide and 4-tert-butyl-aniline. Calculated for C19H21N3O m/z: 307.3, found 308.4 [M+H]+.
Reaction SMILES: C[O:2][C:3]([C:5]1[O:6][C:7](/[CH:10]=[C:11](/[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])\[CH3:12])=[CH:8][CH:9]=1)=[O:4].[OH-].[Li+].Cl>CO>[C:16]([O:15][C:13](/[C:11](/[CH3:12])=[CH:10]/[C:7]1[O:6][C:5]([C:3]([OH:4])=[O:2])=[CH:9][CH:8]=1)=[O:14])([CH3:19])([CH3:17])[CH3:18]
Reactant: COC(=O)c1ccc(/C=C(\C)C(=O)OC(C)(C)C)o1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: C/C(=C\c1ccc(C(=O)O)o1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1.67 h

Procedure:
5-[(1E)-2-(tert-butoxycarbonyl)-prop-1-en-1-yl]furan-2-carboxylic acid methyl ester (1.11 g, 4.17 mmol) obtained in step 1 was dissolved in methanol (7.65 mL), 1N aqueous lithium hydroxide solution (6.25 mL, 6.25 mmol) was added, and the mixture was stirred at room temperature for 100 minutes. 1N aqueous hydrochloric acid solution (6.25 mL) was added, the mixture was stirred for 10 minutes, and the solvent was evaporated under reduced pressure. To the residue were added ethyl acetate and 0.5N aqueous hydrochloric acid solution, the organic layer was extracted, and the aqueous layer was extracted three times with ethyl acetate. The organic layers were collected, washed with saturated brine and dried by dehydration with sodium sulfate. The solvent of the filtrate after filtration was evaporated under reduced pressure to give the title compound.
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:30]=[CH:31][CH:32]=1)[CH2:6][NH:7][C:8](=[O:29])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH:18]=[CH:17][C:16]=2[N+:26]([O-])=O)[CH:10]=1>[Pd].CO>[F:33][C:2]([F:1])([F:34])[C:3]1[CH:4]=[C:5]([CH:30]=[CH:31][CH:32]=1)[CH2:6][NH:7][C:8](=[O:29])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH:18]=[CH:17][C:16]=2[NH2:26])[CH:10]=1
Reactant: CCN(CC)c1ccc([N+](=O)[O-])c(-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Agent: [Pd]
Solvent: CO
Product: CCN(CC)c1ccc(N)c(-c2cc(C(=O)NCc3cccc(C(F)(F)F)c3)ccn2)c1
Reaction time: 2 h
Yield: 89.7 %

Procedure:
A mixture of 500 mg of N-(3-(trifluoromethyl)benzyl)-2-(5-(diethylamino)-2-nitrophenyl)isonicotinamide, 120 mg of 10% Pd/C, and 30 mL of methanol was stirred for 2 h under a hydrogen atmosphere. The mixture was filtered and concentrated to give 0.42 g of product.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH2:16][CH2:17][O:18][CH3:19])[CH3:15])[C:11]([Cl:20])=[CH:10][C:9]=1[NH2:21])([CH3:4])([CH3:3])[CH3:2].C([O:27][C:28](=O)[CH2:29][C:30](=[O:50])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[C:41]([CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)=[CH:40][N:39]=[N:38]2)[CH:32]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH2:16][CH2:17][O:18][CH3:19])[CH3:15])[C:11]([Cl:20])=[CH:10][C:9]=1[NH:21][C:28](=[O:27])[CH2:29][C:30](=[O:50])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[C:41]([CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)=[CH:40][N:39]=[N:38]2)[CH:32]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2nncc2COC2CCCCO2)c1
Reactant: COCCN(C)c1cc(NC(=O)OC(C)(C)C)c(N)cc1Cl
Product: COCCN(C)c1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-n3nncc3COC3CCCCO3)c2)cc1Cl

Procedure:
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (200 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH:7]2[C:13]3=[CH:14][CH:15]=[CH:16][N:12]3[CH2:11][C:10]3[CH:17]=[CH:18][CH:19]=[CH:20][C:9]=3[O:8]2)[CH2:3][CH2:2]1.CS(O[CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1)(=O)=O.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[F:35][C:34]([F:36])([F:37])[C:31]1[CH:30]=[CH:29][C:28]([CH2:27][CH2:26][N:1]2[CH2:2][CH2:3][CH:4]([CH:7]3[C:13]4=[CH:14][CH:15]=[CH:16][N:12]4[CH2:11][C:10]4[CH:17]=[CH:18][CH:19]=[CH:20][C:9]=4[O:8]3)[CH2:5][CH2:6]2)=[CH:33][CH:32]=1
Reactant: CS(=O)(=O)OCCc1ccc(C(F)(F)F)cc1
Reactant: c1ccc2c(c1)Cn1cccc1C(C1CCNCC1)O2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: FC(F)(F)c1ccc(CCN2CCC(C3Oc4ccccc4Cn4cccc43)CC2)cc1
Temperature: 90 °C

Procedure:
A mixture of 11-(piperidin-4-yl)-5H,11H-pyrrolo[2,1-c][1,4]benzoxazepine (5.07 g, 0.019 mole), (p-trifluoromethylphenyl)ethyl methanesulfonate (6.08 g, 0.023 mole) and K2CO3 (10.7 g) in 150 ml dimethylformamide was heated at 90° C. for 7 hours.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C@@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:30][CH:31]([CH3:35])[C:32](Cl)=[O:33]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C@@H:19]([NH:21][C:32](=[O:33])[CH:31]([CH3:35])[CH3:30])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1
Reactant: CC(C)C(=O)Cl
Reactant: COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)N)c1
Product: COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NC(=O)C(C)C)c1

Procedure:
Prepared as described in Example 1 using (1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl)propan-2-amine (6a, 19 mg, 50 μmol) and 2-methylpropanoyl chloride (16 mg, 150 μmol). Yield 17 mg (74%).
Reaction SMILES: [Cl-].[Cl:2][C:3]1[CH:4]=[CH:5][C:6]2[N:7]([N:9]=[C:10]([CH2:12][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:11]=2)[CH:8]=1.[CH3:32][N:33]1[C:37]([CH:38]=O)=[N:36][C:35]([N:40]2[CH2:44][CH2:43][CH2:42][CH2:41]2)=[N:34]1>>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]2[N:7]([N:9]=[C:10]([CH:12]=[CH:38][C:37]3[N:33]([CH3:32])[N:34]=[C:35]([N:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)[N:36]=3)[N:11]=2)[CH:8]=1
Reactant: Clc1ccc2nc(C[P+](c3ccccc3)(c3ccccc3)c3ccccc3)nn2c1
Reactant: Cn1nc(N2CCCC2)nc1C=O
Agent: [Cl-]
Product: Cn1nc(N2CCCC2)nc1C=Cc1nc2ccc(Cl)cn2n1
Yield: 91.1 %

Procedure:
The desired product was prepared in analogy to Example 1 g) from ((6-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)triphenylphosphonium chloride (170 mg, 366 μmol, Eq: 1.00) and 1-methyl-3-(pyrrolidin-1-yl)-1H-1,2,4-triazole-5-carbaldehyde (66.0 mg, 366 μmol, Eq: 1.00). 110 mg (91%) of the desired product were obtained as a light yellow solid. MS: m/z=330.4 (M+H+)
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[Br:12][CH2:13][CH2:14][CH2:15]Br>>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:15][CH2:14][CH2:13][Br:12])=[CH:6][CH:5]=1
Reactant: BrCCCBr
Reactant: COC(=O)c1ccc(O)cc1
Product: COC(=O)c1ccc(OCCCBr)cc1

Procedure:
The title compound is prepared in a manner substantially analogous to Procedure A starting from 4-hydroxy-benzoic acid methyl ester and 1,3-dibromo-propane. MS (ES+) 272.9
Reaction SMILES: [C:1]1([CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[OH:2].[C:9](Cl)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CCCCOCCOCCCC>[C:9]([C:3]1[CH:4]=[C:5]([OH:6])[CH:7]=[CH:8][C:1]=1[OH:2])(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Oc1ccc(O)cc1
Reactant: O=C(Cl)c1ccccc1
Agent: CCCCOCCOCCCC
Product: O=C(c1ccccc1)c1cc(O)ccc1O
Temperature: 110 °C

Procedure:
In the solution of 220 g(2 mol) of hydroquinone in 500 ml of glycol dibutyl ether, 140.5 g(1 mol) of benzoyl chloride was drop-added for one hour while agitating the solution at 110° C. The mixture was maintained at 110° C. for two hours, and diethylene glycol dibutyl ether was distilled under vacuum. 1 liter of methylene chloride was added to the reaction mixture, and the unreacted excess hydroquinone was filtered and collected (recovered amount: 110 g, recycled without any purification process). A desired mono benzoyl hydroquinone was obtained by evaporating the residue under vacuum. (Yield: 207.0 g(97%). mp: 160-162° C., 1H-NMR(300 MHz, CDCl3, ppm) 5.80 (br, 1H), 6.72 (d,2H), 6.89 (d, 2H), 7.44-7.48 (m, 1H), 7.49-7.56 (m, 1H), 8.16 (d, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(Cl)(Cl)Cl.[C:20]([N:25]=[C:26]=[O:27])(=[O:24])[C:21]([CH3:23])=[CH2:22]>ClCCCl>[C:20]([NH:25][C:26](=[O:27])[O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][CH:7]=1)(=[O:24])[C:21]([CH3:23])=[CH2:22]
Reactant: O=C(c1ccccc1)c1ccc(O)cc1
Reactant: C=C(C)C(=O)N=C=O
Solvent: ClC(Cl)Cl
Solvent: ClCCCl
Product: C=C(C)C(=O)NC(=O)Oc1ccc(C(=O)c2ccccc2)cc1
Yield: 100.2 %

Procedure:
Into a three-necked flask purged with nitrogen gas, p-hydroxybenzophenone (1.98 g; 10 mmol) was charged, and chloroform (10 ml) was added thereto. To the resultant solution, a solution of methacryloyl isocyanate (1.11 g; 10 mmol) in 1,2-dichloroethane (5 ml) was dropwise added in 5 minutes under nitrogen stream while stirring. Chloroform and 1,2-dichloroethane were removed by evaporation under reduced pressure to give p-benzoylphenyl N-methacryloylcarbamate (3.1 g), which was recrysallized from a mixture of benzene and chloroform to give white granules. M.P., 96°-97° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:24])[NH:10][N:11]=[CH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.Br[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=1.N>>[F:32][C:29]1[CH:30]=[C:31]([N:10]2[C:9](=[O:24])[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[C:13]([C:14]3[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=3)[CH:12]=[N:11]2)[CH:26]=[CH:27][C:28]=1[F:33]
Reactant: Fc1ccc(Br)cc1F
Reactant: CS(=O)(=O)c1ccc(-c2cn[nH]c(=O)c2-c2ccc(Cl)cc2)cc1
Agent: N
Product: CS(=O)(=O)c1ccc(-c2cnn(-c3ccc(F)c(F)c3)c(=O)c2-c2ccc(Cl)cc2)cc1

Procedure:
The title compound was prepared according to Example 93, starting with 4-(4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 1-bromo-3,4-difluorobenzene in place of 4-bromothioanisole (yield: 310 mg, 65.7%). mp 187-188° C. 1H NMR (300 MHz, CDCl3) δ 3.09 (s, 3H), 7.18 (d, J=9, Hz, 2H), 7.29 (m, 3H), 7.41 (d, J=9 Hz, 2H), 7.52 (m, 1H), 7.65 (m, 1H), 7.92 (d, J=9 Hz, 2H), 8.01 (s, 1H). MS (DCI/NH3) m/z 473(M+H)+, 490 (M+NH4)+. Anal. calc. for C23H15ClF2N2O3S.0.5H2O: C, 57.38; H, 3.33; N, 5.82. Found: C, 57.44; H, 3.38; N, 5.52.
Reaction SMILES: Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][C@@H:4]1[NH:8][C:9](=[O:22])[C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:11]=1[N:17]1[N:21]=[CH:20][CH:19]=[N:18]1.CN1C(=O)CCC1.CCN(C(C)C)C(C)C.Br[C:40]1[N:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][N:41]=1>O>[CH3:16][C:14]1[CH:13]=[CH:12][C:11]([N:17]2[N:18]=[CH:19][CH:20]=[N:21]2)=[C:10]([CH:15]=1)[C:9]([NH:8][C@H:4]1[CH2:5][CH2:6][CH2:7][C@@H:3]1[NH:2][C:40]1[N:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][N:41]=1)=[O:22]
Reactant: Cc1ccc(-n2nccn2)c(C(=O)N[C@H]2CCC[C@@H]2N)c1
Reactant: FC(F)(F)c1cnc(Br)nc1
Agent: Cl
Solvent: O
Solvent: CN1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(-n2nccn2)c(C(=O)N[C@H]2CCC[C@@H]2Nc2ncc(C(F)(F)F)cn2)c1

Procedure:
To a mixture of N-[(1S,2S)-2-aminocyclopentyl]-5-methyl-2-(2H-1,2,3-triazol-2-yl)benzamide hydrochloride (Intermediate 7; 100 mg, 0.31 mmol) and NMP (1 ml) was added DIPEA (0.200 mg, 1.56 mmol) and 2-bromo-5-(trifluoromethyl)pyrimidine (70 mg, 0.31 mmol). The mixture was subjected to microwave irradiation at 150° C. for 1 hour. Upon cooling, the reaction mass was poured into water (5 ml) and extracted with ethyl acetate (2×10 ml). The combined organics were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% ammonia) to afford the title compound.
Reaction SMILES: [CH:1]1([NH:4][C:5]2[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][C:6]=2[S:14](=[O:17])(=[O:16])[NH2:15])[CH2:3][CH2:2]1.[CH3:18]O>S(=O)(=O)(O)O>[CH:1]1([NH:4][C:5]2[CH:13]=[CH:12][C:8]([C:9]([O:11][CH3:18])=[O:10])=[CH:7][C:6]=2[S:14](=[O:17])(=[O:16])[NH2:15])[CH2:2][CH2:3]1
Reactant: CO
Reactant: NS(=O)(=O)c1cc(C(=O)O)ccc1NC1CC1
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(NC2CC2)c(S(N)(=O)=O)c1

Procedure:
4-Cyclopropylamino-3-sulphamoylbenzoic acid (3.9 mmol), prepared according to the process described in Step B of Example 1 starting from the compound obtained in the Step above, is then dissolved in sulphuric acid (0.5 mL) and methanol (10 mL), and the mixture is heated at reflux for 4 hours. The solvent is then removed by distillation under reduced pressure and the residue is suspended in water (20 mL). The precipitate obtained is collected by filtration, washed with water and dried to yield the title product in the form of a white solid.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.Br[CH2:12][CH2:13][OH:14].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([S:1][CH2:12][CH2:13][OH:14])=[N:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(S)nc1
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=[N+]([O-])c1ccc(SCCO)nc1
Temperature: 55 °C
Reaction time: 1 h
Yield: 85 %

Procedure:
A heterogeneous mixture of 2-mercapto-5-nitropyridine (4) (0.50 g, 3.2 mmol), 2-bromoethanol (1) (0.238 mL, 3.3 mmol), and K2CO3 (2.0 g, 14 mmol) in acetone (11 mL) was stirred at 55° C. for 1 h. The cooled reaction mixture was filtered through Celite®, concentrated, and then purified by silica gel chromatography to give 2-[(5-nitro-2-pyridinyl)thio]ethanol (7) as an orange solid (0.545 g, 2.72 mmol). 1H NMR (CDCl3): δ 9.20 (d, J=3.0 Hz, 1H), 8.23 (dd, J=3.0 and 8.7 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 3.94 (t, J=6.0 Hz, 2H), 3.46 (d, J=6.0 Hz, 2H); LCMS: purity: 96%; MS (m/e): 201(MH+).
Reaction SMILES: [Br:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]([CH2:11][CH3:12])[C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.[Si:15]([O:22][C@H:23]1[CH2:32][C@H:31](O)[C@H:30]2[C:25]([CH:26]=[CH:27][C@H:28]([CH3:51])[C@@H:29]2[CH2:34][CH2:35][C@H:36]2[O:41][C:40](=[O:42])[CH2:39][C@H:38]([O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])[CH2:37]2)=[CH:24]1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>>[Si:15]([O:22][C@H:23]1[CH2:32][C@H:31]([O:9][C:8](=[O:10])[CH:7]([O:6][C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:14][CH:13]=2)[CH2:11][CH3:12])[C@H:30]2[C:25]([CH:26]=[CH:27][C@H:28]([CH3:51])[C@@H:29]2[CH2:34][CH2:35][C@H:36]2[O:41][C:40](=[O:42])[CH2:39][C@H:38]([O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:45])[CH3:46])[CH2:37]2)=[CH:24]1)([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:17])[CH3:16]
Reactant: C[C@H]1C=CC2=C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Reactant: CCC(Oc1ccc(Br)cc1)C(=O)O
Product: CCC(Oc1ccc(Br)cc1)C(=O)O[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O3)[C@H]21
Yield: 96 %

Procedure:
A procedure similar to that described in Example 1, above, was followed, but using 0.94 g of (2RS)-2-(4-bromophenoxy)butyric acid and 1.0 g of (4R,6R)-6-{(1S,2S,6S,8S,8aR)-2-[1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsilyloxy-8-hydroxy-2-methyl-1-naphthyl]ethyl}tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example B, above], to give 1.38 g of the title compound as a colorless foam.
Reaction SMILES: [C:1]1([S:7]([NH:10][N:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][C:16]([C:30]([F:33])([F:32])[F:31])=[C:17]([N:22]4[CH:26]=[C:25]([C:27]([OH:29])=[O:28])[N:24]=[CH:23]4)[CH:18]=3)[NH:13][C:12]2=[O:34])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:36]O>>[CH3:36][O:28][C:27]([C:25]1[N:24]=[CH:23][N:22]([C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][C:16]=2[C:30]([F:33])([F:32])[F:31])[NH:13][C:12](=[O:34])[N:11]([NH:10][S:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)(=[O:8])=[O:9])[C:20]3=[O:21])[CH:26]=1)=[O:29]
Reactant: CO
Reactant: O=C(O)c1cn(-c2cc3c(=O)n(NS(=O)(=O)c4ccccc4)c(=O)[nH]c3cc2C(F)(F)F)cn1
Agent: Cl
Product: COC(=O)c1cn(-c2cc3c(=O)n(NS(=O)(=O)c4ccccc4)c(=O)[nH]c3cc2C(F)(F)F)cn1

Procedure:
A solution of 20 mg (0.04 mmol) of 1-(3-benzenesulfonylamino-2,4-dioxo-7-trifluoromethyl-1,2,3,4-tetrahydro-quinazolin-6-yl)-1H-imidazole-4-carboxylic acid in 50 ml of a 6 M solution of hydrochloric acid in methanol is stirred at 70° C. for two days. Every half day another 50 ml of a 6 M solution of hydrochloric acid in methanol is added. Subsequently the solvent and hydrochloric acid are evaporated to yield 1-(3-benzenesulfonylamino-2,4-dioxo-7-trifluoromethyl-1,2,3,4-tetrahydro-quinazolin-6-yl)-1H-imidazole-4-carboxylic acid methyl ester: 1H-NMR; DMSO-d6 (400 MHz, ppm): 8.16 (s, 1H, imidazole); 8.10 (s, 1H, aromatic); 7.98 (s, 1H, imidazole); 7.70 (s, 1H, aromatic); 3.79 (s, 3H, COOCH3). LC-MS: 510 [M+H]+; Agilent LC/MSD 1100 Series, LC-MS method: Column: SunFireC8, 4.6*50 mm, 3.5 μm; positive MS; water/acetonitril 95:5 to 5:95 in 5 min, flow: 1.5 ml/min.
Reaction SMILES: [N:1]([C@@H:4]1[C@@H:11]([O:12]CC2C=CC(OC)=CC=2)[C@H:10]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:9]([CH2:30][O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=2)[O:8][C@H:5]1[S:6][CH3:7])=[N+:2]=[N-:3].C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>C(Cl)Cl.O>[N:1]([C@@H:4]1[C@@H:11]([OH:12])[C@H:10]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@@H:9]([CH2:30][O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=2)[O:8][C@H:5]1[S:6][CH3:7])=[N+:2]=[N-:3]
Reactant: COc1ccc(CO[C@@H]2[C@@H](N=[N+]=[N-])[C@H](SC)O[C@H](COCc3ccc(Cl)cc3)[C@H]2OCc2ccccc2)cc1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: O
Solvent: ClCCl
Product: CS[C@@H]1O[C@H](COCc2ccc(Cl)cc2)[C@@H](OCc2ccccc2)[C@H](O)[C@H]1N=[N+]=[N-]
Temperature: 25 °C
Reaction time: 3 h
Yield: 66 %

Procedure:
A mixture of methyl 2-azido-4-O-benzyl-6-O-(4-chlorobenzyl)-2-deoxy-3-O-(4-methoxybenzyl)-1-thio-β-D glucopyranoside (34) (580 mg, 1.01 mmol) and DDQ (270 mg, 1.2 mmol) in CH2Cl2—H2O 9:1 (10 mL) was stirred at room temperature for 3 hours. The reaction mixture was washed with saturated NaHCO3 solution (3×15 ml), dried over MgSO4 and evaporated. The residue was purified by chromatography using CHCl3-Hexane-MeOH 30:20:0.5 as the mobile phase to give methyl 2-azido-4-O-benzyl-6-O-(4-chlorobenzyl)-2-deoxy-1-thio-β-D glucopyranoside (35) (300 mg, 66%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][CH:17]=[N:18]3)=[C:13]([O:21][CH2:22][C@H:23]3[CH2:27][N:26]([C@@H](C4C=CC=CC=4)C)[C:25](=[O:36])[N:24]3[CH3:37])[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][CH:17]=[N:18]3)=[C:13]([O:21][CH2:22][C@@H:23]3[N:24]([CH3:37])[C:25](=[O:36])[NH:26][CH2:27]3)[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(-c2cc3ncccc3c(OC[C@H]3CN([C@H](C)c4ccccc4)C(=O)N3C)n2)cc1OC
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(-c2cc3ncccc3c(OC[C@H]3CNC(=O)N3C)n2)cc1OC
Temperature: 160 °C

Procedure:
78 mg (R)-4-[7-(3,4-Dimethoxy-phenyl)-[1,6]naphthyridine-5-yloxymethyl]-3-methyl-1-((R)-1-phenyl-ethyl)-imidazolidine-2-one (1.28) was placed in 1 mL of trifluoroacetic acid at ambient temperature. The reaction mixture was heated to 160° C. under microwave irradiation where it was maintained for 10 min. After this time the mixture was cooled to ambient temperature and concentrated under reduced pressure. Purification by silica gel chromatography (methanol/dichloromethane: 1-4%) gave the title compound.
Reaction SMILES: Cl.CC(C)(OC([NH:8][CH:9]([CH3:35])[C:10]([NH:12][C@@H:13]1[CH2:32][CH2:31][C@@:30]2([CH3:33])[C@@H:15]([CH2:16][CH2:17][C@@H:18]3[C@@H:29]2[CH2:28][CH2:27][C@@:26]2([CH3:34])[C@H:19]3[CH2:20][CH2:21][C@@H:22]2[C@@H:23]([OH:25])[CH3:24])[CH2:14]1)=[O:11])=O)C>C(O)C>[NH2:8][CH:9]([CH3:35])[C:10]([NH:12][C@@H:13]1[CH2:32][CH2:31][C@@:30]2([CH3:33])[C@@H:15]([CH2:16][CH2:17][C@@H:18]3[C@@H:29]2[CH2:28][CH2:27][C@@:26]2([CH3:34])[C@H:19]3[CH2:20][CH2:21][C@@H:22]2[C@@H:23]([OH:25])[CH3:24])[CH2:14]1)=[O:11]
Reactant: CC(NC(=O)OC(C)(C)C)C(=O)N[C@@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)O)CC[C@@H]32)C1
Agent: Cl
Solvent: CCO
Product: CC(N)C(=O)N[C@@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)O)CC[C@@H]32)C1
Reaction time: 8 h
Yield: 102.4 %

Procedure:
In a variation, 40 ml of 3.5 N ethanolic hydrochloric acid were added under an inert atmosphere to a solution of 2.7 g of the product of Step A in 10 ml of ethanol and the mixture was stirred for 8 hours and was then evaporated to dryness. The residue was taken up in ethyl acetate and the solution was iced and vacuum filtered. The product was washed with ethyl acetate, was dried at 60° C. under reduced pressure and was crystallized from methanol to obtain 2.2 g of (2S) 2-amino-N-[(20S)-5α-pregnan-20-ol-3α-yl]-propanamide hydrochloride melting at ≃220° C.
Reaction SMILES: [Cl:1][C:2]1[C:16]([Cl:17])=[CH:15][C:5]2[NH:6][C:7]([C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])=[N:8][C:4]=2[CH:3]=1.Br[CH2:19][C:20]#[C:21][CH2:22][CH3:23].[In]>C1COCC1.O.C(OCC)(=O)C>[Cl:17][C:16]1[C:2]([Cl:1])=[CH:3][C:4]2[NH:8][C:7]([C:9]([OH:14])([C:21]([CH2:22][CH3:23])=[C:20]=[CH2:19])[C:10]([F:13])([F:11])[F:12])=[N:6][C:5]=2[CH:15]=1
Reactant: CCC#CCBr
Reactant: O=C(c1nc2cc(Cl)c(Cl)cc2[nH]1)C(F)(F)F
Agent: [In]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: C=C=C(CC)C(O)(c1nc2cc(Cl)c(Cl)cc2[nH]1)C(F)(F)F

Procedure:
1-(5,6-Dichloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanone (2 g), 1-bromo-2-pentyne (1.1 ml) and indium (983 mg) were suspended in THF (15 mL) and H2O (45 mL) and stirred vigorously overnight. The reaction mixture was then diluted with water and ethyl acetate, the layers were separated and the aqueous layer was extracted with ethyl acetate. The combined extracts were washed with brine and dried over Na2SO4 to yield a crude material. The crude material was purified by column chromatography (SiO2; 5-30% ethyl acetate/hexanes) to yield the title compound as a peach-colored solid.