Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[O:10][C:9]3[N:11]=[CH:12][CH:13]=[CH:14][C:8]=3[C:6]=2[N:7]=1.[NH:21]1[C:29]2[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[C:24]=2[CH:23]=[CH:22]1.C(=O)([O-])O.[Na+].C(O)C>O.C1(C)C=CC=CC=1>[NH:21]1[C:29]2[C:24](=[C:25]([C:2]3[N:3]=[C:4]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:5]4[O:10][C:9]5[N:11]=[CH:12][CH:13]=[CH:14][C:8]=5[C:6]=4[N:7]=3)[CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22]1
Reactant: OB(O)c1cccc2[nH]ccc12
Reactant: Clc1nc(N2CCOCC2)c2oc3ncccc3c2n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: c1cc(-c2nc(N3CCOCC3)c3oc4ncccc4c3n2)c2cc[nH]c2c1
Temperature: 120 °C

Procedure:
Under Ar(g), to a mixture of compound 5 (25 mg, 0.086 mmol), indole-4-boronic acid (15.2 mg, 0.095 mmol), dichloro-bis(triphenylphosphine)palladium (II) (3 mg, 0.004 mmol) and sodium hydrogen carbonate (22 mg, 0.26 mmol) was added ethanol (1 mL) followed by toluene (1.6 mL) and then water (0.5 mL). The reaction mixture was then heated in a microwave at 120° C. (300 W) for 45 min, and was subsequently cooled to rt; the mixture was then partitioned between CH2Cl2 and water, and the organic layer was separated, dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica (eluant 30-60% EtOAc/Hex) furnished B (24.5 mg, 0.067 mol, 77%) as an off-white solid.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]([OH:17])=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(C)(C)C.C(N(CC)CC)C.C([Li])CCC.[CH3:37][C@H:38]1[C@@H:42]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[O:41][C:40](=[O:49])[NH:39]1.C(OC(=O)C(C)(C)C)(=O)C(C)(C)C>C1COCC1>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([CH2:14][C:15]([N:39]2[C@@H:38]([CH3:37])[C@@H:42]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[O:41][C:40]2=[O:49])=[O:17])=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)Cc1ccc(Oc2ccccc2)cc1
Reactant: C[C@@H]1NC(=O)O[C@@H]1c1ccccc1
Agent: CC(C)(C)C(=O)Cl
Agent: CC(C)(C)C(=O)OC(=O)C(C)(C)C
Agent: [Li]CCCC
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[C@H]1[C@@H](c2ccccc2)OC(=O)N1C(=O)Cc1ccc(Oc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 64.2 %

Procedure:
To a solution containing 4-phenoxyphenylacetic acid (10.0 g, 43.8 mmol) in THF (62.6 mL) at -78° C. was added pivaloyl chloride (5.49 g, 45.6 mmol) followed by triethylamine (4.61 g, 45.6 mmol). The mixture was stirred at -78° C. for 15 minutes, at 0° C. for 1 hour, and then recooled to -78° C. In a separate flask, 2.5M n-butyllithium (20 mL, 50 mmol) was added to a solution of (4S,5R)-(-)-4-methyl-5-phenyl-2-oxazolidinone (8.86 g, 50 mmol) in THF (100 mL) at -78° C. This mixture was stirred for 15 minutes and then transferred to the flask containing pivalic anhydride via cannula. The mixture was stirred for 15 minutes at -78° C. then at room temperature for 18 hours. The solvent was removed, and the residue was partitioned between diethyl ether (500 mL) and 1N HCl (500 mL). The organic layer was dried (MgSO4), filtered and concentrated to provide a light yellow solid. The solid was chromatographed with 10% ethyl acetate in hexane to yield 10.9 g (64%) of the title compound as a white solid.
Reaction SMILES: C([O:3][C:4](=O)/[C:5](/[F:26])=[C:6](\[C:8]1[CH:9]=[C:10]([CH:23]([CH3:25])[CH3:24])[CH:11]=[C:12]2[C:17]=1[N:16]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:14][C:13]2([CH3:22])[CH3:21])/[CH3:7])C.[H-]>>[F:26]/[C:5](=[C:6](/[C:8]1[CH:9]=[C:10]([CH:23]([CH3:24])[CH3:25])[CH:11]=[C:12]2[C:17]=1[N:16]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:14][C:13]2([CH3:22])[CH3:21])\[CH3:7])/[CH2:4][OH:3]
Reactant: CCCN1CCC(C)(C)c2cc(C(C)C)cc(/C(C)=C(/F)C(=O)OCC)c21
Agent: [H-]
Product: CCCN1CCC(C)(C)c2cc(C(C)C)cc(/C(C)=C(/F)CO)c21

Procedure:
Following General Procedure F, (E)-3-(1-n-propyl-6-isopropyl-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-8-yl)-2-fluoro-but-2-enoic acid ethyl ester (Intermediate 17, 1.43 g, 3.82 mmol) and a 1 M solution of diisobutylalluminum hydride in hexanes (15.3 ml, 15.3 mmol) were reacted to give the title compound as a light yellow oil after purification by flash chromatography (SiO2, first eluted with 5:95 ethyl acetate:hexane, followed by 1:9 ethyl acetate:hexane).
Reaction SMILES: C[O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.[ClH:24]>>[ClH:24].[CH2:16]([N:13]1[CH2:12][CH2:11][N:10]([C:7]2[CH:6]=[CH:5][C:4]([C:3]([OH:23])=[O:2])=[CH:9][CH:8]=2)[CH2:15][CH2:14]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: COC(=O)c1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Agent: Cl
Product: O=C(O)c1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Temperature: 2 °C

Procedure:
4-(4-Benzyl-piperazin-1-yl)-benzoic acid methyl ester (0.84 mmol) is dissolved in 4N HCl (2 ml) and heated under reflux for 8 hours. The mixture is cooled in an ice bath to 0-4° C. and the solid material formed is filtered off, washed with cold acetone and dried (vacuum). A grey powder with mp. >270° C., Rf=0.18 (CH2Cl2/MeOH=95:5) is obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:15]=1)[C:7](=[O:14])[C:8]([C:11]([OH:13])=O)=[CH:9][N:10]=2.C(N(CC)CC)C.ClC(OC)=O.[CH:28]1([NH2:33])[CH2:32][CH2:31][CH2:30][CH2:29]1>C(Cl)(Cl)Cl>[CH:28]1([NH:33][C:11]([C:8]2[C:7](=[O:14])[N:6]3[CH:15]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[O:13])[CH2:32][CH2:31][CH2:30][CH2:29]1
Reactant: Cc1ccc2ncc(C(=O)O)c(=O)n2c1
Reactant: NC1CCCC1
Agent: COC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: Cc1ccc2ncc(C(=O)NC3CCCC3)c(=O)n2c1
Reaction time: 0.08 h
Yield: 49.1 %

Procedure:
A mixture containing 1.22 g (0.006 mol) of 7-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid and 0.84 ml (0.006 mol) of triethylamine in 40 ml of chloroform is cooled below -10° C. by ice-salt. A solution of 0.46 ml (0.006 mol) of methyl chloroformate in 3 ml of chloroform is dropped to the above mixture at -18° C. during 10 minutes. After stirring for 5 minutes, 0.56 g (0.0066 mol) of cyclopentylamine dissolved in 6 ml of chloroform is dropped to the above solution which is then stirred at -10° C. for 1 hour and allowed to stand overnight under cooling by ice. For working up, the reaction mixture is washed 3 times with 15 ml of 5% sodium hydrogen carbonate solution each, then 3 times with 15 ml of water each. The organic phase is dried over anhydrous sodium sulfate, filtered and evaporated to give 0.8 g (49.2%) of the named compound as white crystals after recrystallization from ethanol, m.p.: 162°-164° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([C:28]2[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=2)=[C:8]2[C:12](=[CH:13][C:14]=1[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[C@@H:11]1[CH2:24][CH2:25][CH2:26][N:10]1[C:9]2=[O:27])=[O:5])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:49]([NH2:55])[C:50]1[O:54][CH:53]=[CH:52][CH:51]=1>C1COCC1>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][CH2:15][C:14]2[CH:13]=[C:12]3[C:8]([C:9](=[O:27])[N:10]4[CH2:26][CH2:25][CH2:24][C@H:11]43)=[C:7]([C:28]3[CH:29]=[CH:30][C:31]([C:32]([NH:55][CH2:49][C:50]4[O:54][CH:53]=[CH:52][CH:51]=4)=[O:33])=[CH:35][CH:36]=3)[C:6]=2[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:18][CH:19]=1
Reactant: NCc1ccco1
Reactant: CCOC(=O)c1c(CCc2ccc(F)cc2)cc2c(c1-c1ccc(C(=O)O)cc1)C(=O)N1CCC[C@@H]21
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCOC(=O)c1c(CCc2ccc(F)cc2)cc2c(c1-c1ccc(C(=O)NCc3ccco3)cc1)C(=O)N1CCC[C@@H]21
Temperature: 25 °C
Reaction time: 12 h
Yield: 70000 %

Procedure:
A solution of Example 49 (241 mg, 0.49 mmol) and carbonyldimidazole (0.54 mmol, 88.2 mg) in THF (anhydrous, 15 ml) was stirred for 1 hr at r.t. Then was added dropwise a solution of furfurylamine (96.1 mg, 0.99 mmol) in THF (2 ml) and the mixture stirred at r.t. for 12 hr. Then the reaction mixture concentrated and the yellow oil purified on SiO2 (ethyl acetate:hexanes 1:5) to afford the title compound as a white solid (194 mg, 343 mmol): 1H NMR (400 MHz, d6-DMSO) δ 9.03 (t, 1H), 7.82 (d, J=8.6 Hz, 2H), 7.53 (d, J=8.2 Hz, 2H), 7.26 (d, J=8.2 Hz, 2H), 7.20–7.17 (m, 2H), 7.09–7.04 (m, 2H), 6.36 (d, J=4.0 Hz, 1H), 6.25 (d, J=4.0 Hz, 1H), 4.69–4.65 (m, 1H), 4.46–4.44 (m, 2H), 3.91 (q, 2H), 3.39–3.36 (m, 1H), 3.19–3.13 (m, 1H), 2.90–2.79 (m, 4H), 2.28–2.18 (m, 3H), 1.13–1.08 (m, 1H), 1.08 (t, 3H) ppm. ESI-MS m/z 567 (M+H)+. HPLC (99%). Anal. calcd. for C34H31N2O5F 0.41H2O: C, 71.14; H, 5.59; N, 4.88. Found: C, 71.14; H, 5.66; N, 4.84.
Reaction SMILES: C(O[C@@H:6]1[O:20][C@H:19]([C@@H:21]([CH2:27][O:28][C:29](=[O:32])[CH2:30][CH3:31])[O:22][C:23](=[O:26])[CH2:24][CH3:25])[C@H:13]([O:14][C:15](=[O:18])[CH2:16][CH3:17])[C@H:7]1[O:8][C:9](=[O:12])[CH2:10][CH3:11])(=O)CC.[C:33]1([OH:39])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.B(F)(F)F.CCOCC>C(Cl)Cl>[C:9]([O:8][C@@H:7]1[C@@H:13]([O:14][C:15](=[O:18])[CH2:16][CH3:17])[C@@H:19]([C@@H:21]([CH2:27][O:28][C:29](=[O:32])[CH2:30][CH3:31])[O:22][C:23](=[O:26])[CH2:24][CH3:25])[O:20][C@H:6]1[O:39][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=[O:12])[CH2:10][CH3:11]
Reactant: Oc1ccccc1
Reactant: CCC(=O)OC[C@@H](OC(=O)CC)[C@H]1O[C@@H](OC(=O)CC)[C@H](OC(=O)CC)[C@H]1OC(=O)CC
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: CCC(=O)OC[C@@H](OC(=O)CC)[C@H]1O[C@@H](Oc2ccccc2)[C@H](OC(=O)CC)[C@H]1OC(=O)CC
Reaction time: 8 h
Yield: 75.7 %

Procedure:
1,2,3,5,6-Penta-O-propanoyl-β-D-glucofuranose (1.0 g, 2.2 mmol) and phenol (0.41 g, 4.3 mmol) were dissolved in CH2Cl2 (10 mL) and boron trifluoride diethyl etherate (134 μL, 1.1 mmol) was added dropwise. The solution was left at room temperature overnight by which time the reaction was complete by TLC. The reaction mixture was washed with saturated aqueous NaHCO3 (30 mL), water, dried (MgSO4) and concentrated in vacuo. Flash silica chromatography of the residue, eluting with 15% ethyl acetate in petroleum ether, gave phenyl 2,3,5,6-tetra-O-propanoyl-β-D-glucofuranoside as a colourless syrup (0.8 g, 77%); δH (CDCl3) 7.29 (2H, dd, J 7.4 and 8.4, 3′-and 5′-H), 7.02 (1H, t, J 7.4, 4′-H), 7.01 (2H, d, J 8.4, 2′- and 6′-H), 5.63 (1H, s, 1-H), 5.46 (1H, d, J 5.0, 3-H), 5.31 (1H, ddd, J 9.4, 4.6 and 2.4, 5-H), 5.27 (1H, s, 2-H), 4.62 (1H, dd, J 9.4 and 5.0, 4-H), 4.54 (1H, dd, J 12.3 and 2.4, 6a-H), 4.09 (1H, dd, J 12.3 and 4.6, 6b-H), 2.42 (2H, q, J 7.5, CH2), 2.39 (2H, q, J 7.5, CH2), 2.33 (2H, q, J 7.5, CH2), 2.25 (2H, q, J 7.5, CH2), 1.17 (3H, t, J 7.5, CH3), 1.15 (3H, t, J 7.5, CH3), 1.13 (3H, t, J 7.5, CH3), 1.08 (3H, t, J 7.5, CH3); δC (CDCl3) 174.3, 173.3, 173.3, 173.0 (4×C═O), 156.6 (1′-C), 130.0 (3′- and 5′-C), 122.9 (4′-C), 116.9 (2′- and 6′-C), 104.6 (1-C), 80.7 (2-C), 79.7 (4-C), 73.6 (3-C), 68.9 (5-C), 63.2 (6-C), 27.8, 27.8, 27.8, 27.7 (4×CH2), 9.4, 9.2, 9.2, 9.1 (4×CH3).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])[C:7](Cl)=[O:8])([O-:3])=[O:2].[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][N:18]=1.N1C=CC=CC=1>C1(C)C=CC=CC=1>[C:23]([C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:7](=[O:8])[C:6]2[CH:10]=[CH:11][C:12]([N+:13]([O-:15])=[O:14])=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[N:18][CH:19]=1)#[N:24]
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])c([N+](=O)[O-])c1
Reactant: N#Cc1ccc(N)nc1
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: N#Cc1ccc(NC(=O)c2ccc([N+](=O)[O-])c([N+](=O)[O-])c2)nc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3,4-Dinitro-benzoyl chloride (0.69 g, 3.0 mmol) in 2 mL toluene was added to a stirred mixture of 2-amino-5-cyanopyridine (0.357 g, 3.0 mmol) and 5 mL pyridine. After stirring overnight at ambient temperature the mixture was concentrated i.vac. The residue was taken up in ethyl acetate and 5% NaHCO3 (aq). The organic layer was washed with water and brine, separated, dried and concentrated i.vac. The residue was purified by chromatography on silica gel (eluent gradient: dichloromethane/ethanol=100:0->100:2).
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]([NH:5][CH:6]([CH3:17])[CH2:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=1[I:16])=[O:4].C([O-])([O-])=O.[K+].[K+].[OH-].[K+].[CH2:28](Br)[CH:29]=[CH2:30].Cl>C1(C)C=CC=CC=1.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-]>[CH2:30]([N:5]([CH:6]([CH3:17])[CH2:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=1[I:16])[C:3](=[O:4])[C:2]([F:1])([F:18])[F:19])[CH:29]=[CH2:28]
Reactant: C=CCBr
Reactant: COc1ccc(I)c(CC(C)NC(=O)C(F)(F)F)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: C=CCN(C(=O)C(F)(F)F)C(C)Cc1cc(OC)ccc1I
Reaction time: 8 h
Yield: 66.3 %

Procedure:
A solution of N-trifluoroacetyl-1-(2-iodo-5-methoxyphenyl)-2-propylamine (6.09 g, 15.7 mmol) in toluene (450 mL) was treated with K2CO3 (2.82 g, 20.4 mmol), KOH (2.45 g, 47.1 mmol), n-Bu4NBr (0.506 g, 1.57 mmol) and allyl bromide (2.47 g, 20.4 mmol), and stirred overnight at 80 C. The product mixture was acidified with 10% aqueous HCl, separated, the aqueous phase extracted with ether (500 mL), the combined organic phases were washed with brine (200 mL), dried with Na2SO4 ari concentrated to give 4.45 g of a brown oil.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39](=[O:61])[N:40]([CH2:51][CH2:52][O:53][Si](C(C)(C)C)(C)C)[CH2:41][CH2:42][O:43][Si](C)(C)C(C)(C)C)=[CH:33][CH:32]=1)[C:9](=[O:30])[NH:10][CH:11]([C:20]1[NH:24][C:23]2[CH:25]=[C:26]([I:29])[CH:27]=[CH:28][C:22]=2[N:21]=1)[CH:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][C@H:8]([C:31]1[CH:32]=[CH:33][C:34]([O:37][CH2:38][C:39](=[O:61])[N:40]([CH2:51][CH2:52][OH:53])[CH2:41][CH2:42][OH:43])=[CH:35][CH:36]=1)[C:9]([NH:10][C@H:11]([C:20]1[NH:24][C:23]2[CH:25]=[C:26]([I:29])[CH:27]=[CH:28][C:22]=2[N:21]=1)[C@H:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])=[O:30]
Reactant: CC(c1ccccc1)C(NC(=O)C(NC(=O)OC(C)(C)C)c1ccc(OCC(=O)N(CCO[Si](C)(C)C(C)(C)C)CCO[Si](C)(C)C(C)(C)C)cc1)c1nc2ccc(I)cc2[nH]1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H](c1ccccc1)[C@H](NC(=O)[C@H](N)c1ccc(OCC(=O)N(CCO)CCO)cc1)c1nc2ccc(I)cc2[nH]1
Temperature: 0 °C
Reaction time: 1 h
Yield: 93.8 %

Procedure:
{[4-({Bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamoyl}-methoxy)-phenyl]-[1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propylcarbamoyl]-methyl}-carbamic acid tert-butyl ester (270 mg, 0.27 mmol) was dissolved in dry dichloromethane (6 mL) and cooled in an ice bath. To the stirred solution was added triflouroacetic acid (3.12 mL, 40.5 mmol). The reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was concentrated in vacuo, dissolved in dichloromethane (1 mL) and the crude trifluoroacetate salt precipitated with ether (5 mL) and pentane (10 mL). The precipitate was triturated then filtered. The solid was taken into dichloromethane (50 mL) and tetrahydrofuran added to form a clear solution. The solution was washed with saturated aqueous sodium hydrogen carbonate (2×50 mL), the layers separated and the aqueous layer extracted with dichloromethane (4×50 mL). The combined organic extracts were dried over sodium sulfate filtered and concentrated in vacuo. The resulting solid was triturated with a mixture of ether (1 mL) and pentane (5 mL), filtered and dried to give (R)-2-amino-2-(4-{[bis-(2-hydroxy-ethyl)-carbamoyl]-methoxy}-phenyl)-N-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-acetamide (170 mg, 93.8%).
Reaction SMILES: C([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][NH:17][CH2:18][C:19]([O:21]C)=[O:20])([O:6]CC)=[O:5])C.[ClH:23]>>[ClH:23].[P:4]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][NH:17][CH2:18][C:19]([OH:21])=[O:20])([OH:6])([OH:5])=[O:3]
Reactant: CCOP(=O)(Cc1ccccc1CNCC(=O)OC)OCC
Agent: Cl
Product: O=C(O)CNCc1ccccc1CP(=O)(O)O

Procedure:
A solution of methyl N-[[2[(diethoxyphosphinyl)methyl]phenyl]methyl]glycinate (Example 1) (0.5 g, 1.5 mmol) in 6N hydrochloric acid solution (10 ml) is stirred at reflux in an oil bath for 18 hours. The water is removed in vacuo to give 0.4 g of a white solid.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11]2([CH2:18][CH2:17][N:16]([C:19]([N:21]3[C@@:25]([C:27]4[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=4)([CH3:26])[C@@:24]([C:35]4[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=4)([CH3:34])[N:23]=[C:22]3[C:42]3[CH:43]=[N:44][C:45]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:46][C:47]=3[O:48][CH2:49][CH3:50])=[O:20])[CH2:15][CH2:14]2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>>[C:51]([C:45]1[N:44]=[CH:43][C:42]([C:22]2[N:21]([C:19]([N:16]3[CH2:15][CH2:14][C:11]4([CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)[CH2:18][CH2:17]3)=[O:20])[C@@:25]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)([CH3:26])[C@@:24]([C:35]3[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=3)([CH3:34])[N:23]=2)=[C:47]([O:48][CH2:49][CH3:50])[CH:46]=1)([CH3:52])([CH3:53])[CH3:54]
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC2(CCN(C(=O)OC(C)(C)C)CC2)CC1
Solvent: O=C(O)C(F)(F)F
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC2(CCNCC2)CC1

Procedure:
9-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-3,9-diaza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (example 74) was treated with trifluoroacetic acid to give the title compound. HR-MS (ES, m/z) calculated for C38H48Cl2N5O2 [(M+H)+] 676.318, observed 676.3177.
Reaction SMILES: [CH3:1][C:2]1[C:19]([C:20]#[N:21])=[C:6]2[N:7]=[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N+:16]([O-])=O)[O:9][C:5]2=[C:4]([N:22]2[CH2:26][CH2:25][C@H:24]([N:27]([CH3:29])[CH3:28])[CH2:23]2)[C:3]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[H][H]>[C].[Pd].C(OCC)(=O)C>[NH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[C:8]1[O:9][C:5]2[C:6](=[C:19]([C:20]#[N:21])[C:2]([CH3:1])=[C:3]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:4]=2[N:22]2[CH2:26][CH2:25][C@H:24]([N:27]([CH3:28])[CH3:29])[CH2:23]2)[N:7]=1
Reactant: Cc1c(-c2ccccc2)c(N2CC[C@H](N(C)C)C2)c2oc(-c3ccccc3[N+](=O)[O-])nc2c1C#N
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cc1c(-c2ccccc2)c(N2CC[C@H](N(C)C)C2)c2oc(-c3ccccc3N)nc2c1C#N
Yield: 55 %

Procedure:
10% Palladium-carbon (150 mg) was added to an ethyl acetate (30 ml) solution of 5-methyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-(2-nitrophenyl)-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-211) (128 mg, 0.27 mmol), followed by stirring at the same temperature under atmospheric pressure of hydrogen for 1.5 hours. The catalyst was removed by filtration with washing with ethyl acetate, the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography. Elution with a mixed solvent of chloroform/methanol (99:1→96:4, v/v) gave the entitled compound (65 mg, 55%) as a pale yellow solid.
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:13][C@@H:12]([N:14]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)C(=O)C(F)(F)F)[CH2:11][CH2:10][N:9]1[C:29](=[O:38])[C:30]1[CH:35]=[C:34]([Cl:36])[CH:33]=[C:32]([Cl:37])[CH:31]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>>[CH2:1]([C@@H:8]1[CH2:13][C@@H:12]([NH:14][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:11][CH2:10][N:9]1[C:29](=[O:38])[C:30]1[CH:31]=[C:32]([Cl:37])[CH:33]=[C:34]([Cl:36])[CH:35]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(c1cc(Cl)cc(Cl)c1)N1CC[C@H](N(CCc2ccccc2)C(=O)C(F)(F)F)C[C@H]1Cc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Product: O=C(c1cc(Cl)cc(Cl)c1)N1CC[C@H](NCCc2ccccc2)C[C@H]1Cc1ccccc1

Procedure:
0.130 g (0.231 mmol) of (2R*,4S*)-2-benzyl-1-(3,5-dichlorobenzoyl)-N-(2-phenylethyl)-N-trifluoroacetyl-4-piperidinamine is reacted with 0.035 g (0.923 mmol) of sodium borohydride in analogy to Example 2. The title compound ##STR81## is obtained (0.101 g, 94%) as oil. TLC: methylene chloride/methanol/conc. ammonia (700:50:1) Rf =0.34, FD-MS: M+ =466, 468.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1[Cl:10])=O.[Cl:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[NH:17])=[CH:14][CH:13]=1>C(Cl)(Cl)Cl>[Cl:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]2[NH:17][C:3]([C:5]3[S:6][CH:7]=[CH:8][C:9]=3[Cl:10])=[CH:2][N:18]=2)=[CH:14][CH:13]=1
Reactant: N=C(N)c1ccc(Cl)cc1
Reactant: O=C(CBr)c1sccc1Cl
Solvent: ClC(Cl)Cl
Product: Clc1ccc(-c2ncc(-c3sccc3Cl)[nH]2)cc1

Procedure:
Compounds of this invention with Formula IV may be prepared as illustrated by the exemplary reaction in Scheme 3. Reaction of 2-bromo-1-(3-chloro-thiophen-2-yl)-ethanone with 4-chloro-benzamidine in chloroform produces the product 2-(4-chloro-phenyl)-5-(3-chloro-thiophen-2-yl)-1H-imidazole.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]([N+:13]([O-])=O)([CH2:11][OH:12])[CH2:9][OH:10])[CH:5]=[CH:6][CH:7]=1.[H][H]>CCO.[Ni]>[NH2:13][C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)([CH2:11][OH:12])[CH2:9][OH:10]
Reactant: [H][H]
Reactant: O=[N+]([O-])C(CO)(CO)c1cccc(Br)c1
Agent: [Ni]
Solvent: CCO
Product: NC(CO)(CO)c1cccc(Br)c1

Procedure:
A solution of 2-(3-bromo-phenyl)-2-nitro-propane-1,3-diol (6.79 g, 24.59 mmol) in 100 ml of EtOH was hydrogenated in the presence of 5 g of Raney-Ni. When the take-up of hydrogen had ceased, the mixture was filtered through Celite, and the filtrate was chromatographed on silica gel (EtOAc/MeOH/25% aqueous NH3, 5%) to give the title compound in the form of a colourless solid. TLC (EtOAc/MeOH/25% aqueous NH3, 5%): Rf=0.24; HPLC: RtH2=2.354 min; 1H-NMR (400 MHz, CD3OD): 7.73 (s, 1H), 7.50 (d, 1H), 7.44 (d, 1H), 7.29 (t, 1H), 3.79 (d, 2H), 3.72 (d, 2H); MS: 246, 248 [(M+H)+].
Reaction SMILES: C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[CH:16]=[C:17]([C:21]3[CH:26]=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)[CH:24]=[C:23]([CH3:37])[N:22]=3)[CH:18]=[N:19][CH:20]=2)[CH:10]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[CH3:37][C:23]1[N:22]=[C:21]([C:17]2[CH:18]=[N:19][CH:20]=[C:15]([C:11]3[CH:10]=[C:9]([S:6]([NH2:5])(=[O:8])=[O:7])[CH:14]=[CH:13][CH:12]=3)[CH:16]=2)[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:29][CH:28]=2)[CH:24]=1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cncc(-c3cccc(S(=O)(=O)NC(C)(C)C)c3)c2)n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cncc(-c3cccc(S(N)(=O)=O)c3)c2)n1
Yield: 95.5 %

Procedure:
To a stirred and cooled suspension of N-tert-butyl-3-[6-methyl-4-(4-trifluoromethylphenyl)-[2,3′]bipyridinyl-5′-yl]-benzenesulfonamide (example 288) (0.150 g, 0.29 mmol) in dichloromethane (0.9 mL) was added TFA (6.3 mL) and the reaction mixture was allowed to stir at room temperature for 16 h. The mixture was evaporated to dryness and saturated NaHCO3 solution (5 mL), diethyl ether and heptane were added. The mixture was stirred at room temperature for 1 h, the precipitate was collected by filtration, washed with water and heptane/diethyl ether and dried to yield the title compound as a white solid (0.130 g, 97%). MS (ISP) 470.3 [(M+H)+]; mp 235° C. (dec.).