Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:11]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][C:14]=2[F:21])[CH:9]=[CH:8][C:5]=1[C:6]#[N:7].Cl[C:23]1[CH:24]=[C:25]2[N:32]([CH3:33])[CH2:31][CH2:30][N:26]2[C:27](=[O:29])[N:28]=1>C1COCC1>[F:3][C:4]1[CH:11]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][O:20][C:23]3[CH:24]=[C:25]4[N:32]([CH3:33])[CH2:31][CH2:30][N:26]4[C:27](=[O:29])[N:28]=3)=[CH:15][C:14]=2[F:21])[CH:9]=[CH:8][C:5]=1[C:6]#[N:7]
Reactant: CN1CCn2c1cc(Cl)nc2=O
Reactant: N#Cc1ccc(Oc2ccc(CO)cc2F)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN1CCn2c1cc(OCc1ccc(Oc3ccc(C#N)c(F)c3)c(F)c1)nc2=O

Procedure:
Prepared in a manner similar to that described for E1 using sodium hydride (5.51 mg, 0.230 mmol) in THF (5 mL), 2-fluoro-4-(2-fluoro-4-(hydroxymethyl)phenoxy)benzonitrile (30 mg, 0.115 mmol) and 7-chloro-1-methyl-2,3-dihydroimidazo[1,2-c]pyrimidin-5(1H)-one (21.3 mg, 0.115 mmol).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[CH:9]=[C:10]([C:14]3[CH:19]=[CH:18][N:17]4[C:20]([C:23]5[CH:24]=[C:25]([NH:29][C:30]([NH:32][CH2:33][C:34]([F:37])([F:36])[F:35])=[O:31])[CH:26]=[CH:27][CH:28]=5)=[CH:21][N:22]=[C:16]4[CH:15]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:3][CH2:2]1.[C:38](Cl)(=[O:40])[CH3:39].CCN(CC)CC>CN(C=O)C>[C:38]([N:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[CH:9]=[C:10]([C:14]3[CH:19]=[CH:18][N:17]4[C:20]([C:23]5[CH:24]=[C:25]([NH:29][C:30]([NH:32][CH2:33][C:34]([F:35])([F:36])[F:37])=[O:31])[CH:26]=[CH:27][CH:28]=5)=[CH:21][N:22]=[C:16]4[CH:15]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:3][CH2:2]1)(=[O:40])[CH3:39]
Reactant: O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4cccc(OC5CCNCC5)c4)ccn23)c1
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(=O)N1CCC(Oc2cccc(-c3ccn4c(-c5cccc(NC(=O)NCC(F)(F)F)c5)cnc4c3)c2)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 1-(3-{7-[3-(Piperidin-4-yloxy)-phenyl]-imidazo[1,2-a]pyridine-3-yl}-phenyl)-3-(2,2,2-trifluoro-ethyl)-urea (50 mg, 98 μmol in DMF(10 ml) was added acetyl chloride (6.3 μl, 82 μmol) and Et3N (14 μl). The reaction was stirred at room temperature for 3 h, then partitioned between EtOAc and H2O. The aqueous layer was again extracted with EtOAc, the organics combined, dried (MgSO4), filtered and the solvent removed in vacuo. The residue was purified by preparative HPLC to give the title compound (17.5 mg).
Reaction SMILES: [CH3:1]OC1C=CC(N2C(=O)C(C(C)C)NC2=O)=CC=1.N1C2C(=CC=CC=2)[CH:21]=[C:20]1[CH2:28][CH:29]1[NH:33][C:32](=[O:34])[N:31]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:30]1=[O:43].COC1C=CC(N2C(=O)C(C3C=CC=CC=3)(C3C=CC=CC=3)NC2=O)=CC=1>>[CH3:42][O:41][C:38]1[CH:37]=[CH:36][C:35]([N:31]2[C:30](=[O:43])[CH:29]([CH2:28][CH:20]([CH3:21])[CH3:1])[NH:33][C:32]2=[O:34])=[CH:40][CH:39]=1
Reactant: COc1ccc(N2C(=O)NC(Cc3cc4ccccc4[nH]3)C2=O)cc1
Reactant: COc1ccc(N2C(=O)NC(C(C)C)C2=O)cc1
Agent: COc1ccc(N2C(=O)NC(c3ccccc3)(c3ccccc3)C2=O)cc1
Product: COc1ccc(N2C(=O)NC(CC(C)C)C2=O)cc1

Procedure:
3-(4-methoxyphenyl)-5-(1-methylethyl)-2,4-imidazolidinedione; 5-(1H-indol-2-ylmethyl)-3-(4-methoxyphenyl)-2,4-imidazolidinedione; 3-(4-methoxyphenyl)-5,5-diphenyl-2,4-imidazolidinedione; are set forth in Table 2.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18]1[O:22][C:21]([C:23]([NH:25][C:26]2[CH:27]=[N:28][C:29]([N:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)=[CH:30][CH:31]=2)=[O:24])=[N:20][N:19]=1>CN(C=O)C>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18]1[O:22][C:21]([C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([N:32]3[CH2:37][CH2:36][N:35]([C:8]([NH:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[O:9])[CH2:34][CH2:33]3)=[N:28][CH:27]=2)=[O:24])=[N:20][N:19]=1
Reactant: O=C=Nc1ccccc1
Reactant: O=C(Nc1ccc(N2CCNCC2)nc1)c1nnc(Nc2ccccc2F)o1
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(N2CCN(C(=O)Nc3ccccc3)CC2)nc1)c1nnc(Nc2ccccc2F)o1
Yield: 21.4 %

Procedure:
Phenyl isocyanate (0.032 mL, 0.29 mmol) was added to a stirred mixture of 5-[(2-fluorophenyl)amino]-N-(6-piperazin-1-ylpyridin-3-yl)-1,3,4-oxadiazole-2-carboxamide (Intermediate 41, 100 mg, 0.26 mmol) and DMF (1.5 mL). After 2 h the crude reaction mixture was directly purified by reverse phase HPLC eluting with a gradient of acetonitrile/water containing 0.2% TFA to give the title compound (28 mg, 20%) as a solid; 1H NMR δ 11.00 (1H, s), 10.74 (1H, s), 8.55 (1H, s), 8.50 (1H, s), 8.05-7.95 (2H, m), 7.45 (2H, d), 7.35-7.10 (4H, m), 7.00 (1H, d), 6.90 (1H, t), 3.80-3.60 (8H, m); MS m/e MH+ 503.
Reaction SMILES: [C@H:1]12[CH2:8][CH2:7][CH2:6][C@H:5]1[CH2:4][NH:3][C@@H:2]2[CH2:9][NH:10][C:11]([C:13]1[N:20]2[C:16]([S:17][CH:18]=[CH:19]2)=[N:15][C:14]=1[CH3:21])=[O:12].[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[C:30]([C:35](O)=[O:36])=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:25][CH:24]=1>>[F:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]2[C:30]([C:35]([N:3]3[CH2:4][C@H:5]4[C@H:1]([CH2:8][CH2:7][CH2:6]4)[C@H:2]3[CH2:9][NH:10][C:11]([C:13]3[N:20]4[C:16]([S:17][CH:18]=[CH:19]4)=[N:15][C:14]=3[CH3:21])=[O:12])=[O:36])=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:27][CH:28]=1
Reactant: O=C(O)c1ccccc1-c1ccc(F)cc1
Reactant: Cc1nc2sccn2c1C(=O)NC[C@H]1NC[C@@H]2CCC[C@@H]21
Product: Cc1nc2sccn2c1C(=O)NC[C@@H]1[C@H]2CCC[C@H]2CN1C(=O)c1ccccc1-c1ccc(F)cc1

Procedure:
prepared by reaction of 6-methyl-imidazo[2,1-b]thiazole-5-carboxylic acid-[(1S,2S,5R)-3-aza-bicyclo[3.3.0]oct-2-ylmethyl]-amide with commercially available 4′-fluoro-biphenyl-2-carboxylic acid.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]2[CH:13]=[CH:14][CH:15]=[C:16]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][C:22]([C:25](=[O:27])[CH3:26])=[C:21]([OH:28])[C:20]=3[CH2:29][CH2:30][CH3:31])[C:9]2=[N:8][CH:7]=1)=[O:5])C.Cl>C(O)(=O)C>[C:25]([C:22]1[CH:23]=[CH:24][C:19]([O:18][CH2:17][C:16]2[C:9]3=[N:8][CH:7]=[C:6]([C:4]([OH:5])=[O:3])[C:11](=[O:12])[N:10]3[CH:13]=[CH:14][CH:15]=2)=[C:20]([CH2:29][CH2:30][CH3:31])[C:21]=1[OH:28])(=[O:27])[CH3:26]
Reactant: CCCc1c(OCc2cccn3c(=O)c(C(=O)OCC)cnc23)ccc(C(C)=O)c1O
Agent: Cl
Solvent: CC(=O)O
Product: CCCc1c(OCc2cccn3c(=O)c(C(=O)O)cnc23)ccc(C(C)=O)c1O
Temperature: 80 °C
Yield: 50 %

Procedure:
0.90 g (2.12 mmoles) of 9-(4-acetyl-3-hydroxy-2-n-propylphenoxymethyl)-4-oxo-pyrido[1,2-a]pyrimidine-3carboxylic acid ethyl ester and 8 ml of 6N hydrochloric acid were added to 36 ml of acetic acid, and this mixture was heated at 80° C. for 8 hours with stirring. After cooling, the resulting reaction solution was concentrated under reduced pressure, followed by the addition of an appropriate amount of water. The solid matter which separated out was collected by filtration and washed with water. This precipitate was dried and then recrystallized from a mixture of tetrahydrofuran and methanol to obtain 0.42 g (50% yield) of 9-(4-acetyl-3-hydroxy-2-n-propylphenoxymethyl)-4-oxo-pyrido[1,2-a]-pyrimidine-3-carboxylic acid in the form of white crystals. These crystals had a melting point of 170°-172° C.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C@@H:12]1[O:16][C:15](=[O:17])[NH:14][C@H:13]1[CH3:18].[H-].[Na+].[F:21][C:22]([F:36])([F:35])[C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH2:26]Br>>[F:21][C:22]([F:35])([F:36])[C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:30]=1)[CH2:26][N:14]1[C@@H:13]([CH3:18])[C@H:12]([C:3]2[CH:4]=[C:5]([C:8]([F:9])([F:10])[F:11])[CH:6]=[CH:7][C:2]=2[I:1])[O:16][C:15]1=[O:17]
Reactant: C[C@@H]1NC(=O)O[C@H]1c1cc(C(F)(F)F)ccc1I
Reactant: FC(F)(F)c1cc(CBr)cc(C(F)(F)F)c1
Agent: [H-]
Agent: [Na+]
Product: C[C@H]1[C@H](c2cc(C(F)(F)F)ccc2I)OC(=O)N1Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1

Procedure:
Following the procedure described in EXAMPLE 96, 0.108 g of (4S,5S)-5-[2-iodo-5-(trifluoromethyl)phenyl]4-methyl-1,3-oxazolidin-2-one, 23 mg of sodium hydride, and 107 mg of 3,5-bis(trifluoromethyl)benzyl bromide provided the title compound. Mass spectrum (ESI) 598.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.00 (d, J=8.5 Hz, 1H), 7.77 (s, 1H), 7.58 (br s, 3H), 7.34 (dd, J=1.5 Hz, 8 Hz, 1H), 5.36 (d, J=4 Hz, 1H), 4.89 (d, J=16 Hz, 1H), 4.31 (d, J=16 Hz, 1H), 4.48 (dq, J=6 Hz, 4 Hz, 1H), 1.55 (d, J=6.5 Hz, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].C1(=O)NC(=O)C2=CC=CC=C12.Br[CH2:22][CH:23]([OH:25])[CH3:24].BrC[C@H](C)OC1CCCCO1.[H-].[Na+]>O1CCCC1.CN(C)C=O>[NH2:1][C:2]1[CH:3]=[C:4]([CH2:5][O:6][CH2:22][C@@H:23]([OH:25])[CH3:24])[CH:7]=[CH:8][CH:9]=1
Reactant: CC(O)CBr
Reactant: Nc1cccc(CO)c1
Agent: C[C@@H](CBr)OC1CCCCO1
Agent: O=C1NC(=O)c2ccccc21
Agent: [H-]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: C[C@H](O)COCc1cccc(N)c1

Procedure:
The manner in which optically active forms of arylmethoxy aliphatic amines, such as (2S)-N-methyl-1-[(3-aminophenyl)methoxy]-propan-2-amine type compounds, are provided can vary. In one approach, a 3-aminobenzyl alcohol type compound (N-protected as the phthalimide) can be alkylated with a chiral 1-bromo-2-propanol type compound containing an O-protecting group, such as (1S)-2-(2-bromo-1-methylethoxy)tetrahydro-2H-pyran using a base such as sodium hydride and a solvent such as N,N-dimethylformamide or tetrahydrofuran. The tetrahydropyranyl protecting group of the resulting chiral arylmethyl ether type compound can be removed with aqueous sulfuric acid in methanol, affording (2S)-1-[(3-aminophenyl)methoxy]-propan-2-ol. The resulting chiral alcohol intermediate can be converted to its corresponding tosylate, followed by tosylate displacement with methylamine with inversion of configuration, and finally removal of the N-phthaloyl group to give the chiral amine (2R)-N-methyl-1-[(3-aminophenyl)methoxy]-propan-2-amine. Chiral side chain compounds such as (1S)-2-(2-bromo-1-methylethoxy)tetrahydro-2H-pyran can be prepared from (2S)-1-bromo-2-propanol by treatment with 3,4-dihydro-2H-pyran in dichloromethane with p-toluenesulfonic acid as a catalyst according to the method of S. A. M. Nieuwenhuis et al., Tetrahedron 50: 13207-13230 (1994). The required (2S)-1-bromo-2-propanol can be obtained from (S)-propylene oxide (commercially available from Fluka) by treatment with hydrogen bromide in acetic acid at 0° C. The corresponding optical antipode, (2R)-N-methyl-1-[(3-aminophenyl)methoxy]-propan-2-amine can be prepared in an analogous manner from (R)-propylene oxide (commercially available from Fluka) by using the synthetic procedure of S. A. M. Nieuwenhuis et al. to prepare the tetrahydropyranyl ether of (2R)-1-bromo-2-propanol and by using the synthetic sequence described above.
Reaction SMILES: [C:1]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[Li+].[N-:15]=[N+:16]=[N-:17].[Na+].[Br-].C([NH+](CC)CC)C.Cl>CN(C=O)C.O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9]2[NH:17][N:16]=[N:15][N:10]=2)=[CH:11][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)c1ccc(C#N)cc1
Agent: CC[NH+](CC)CC
Agent: Cl
Agent: [Br-]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)c1ccc(-c2nnn[nH]2)cc1
Temperature: 25 °C

Procedure:
4.99 of p-t-butylbenzonitrile, 3.82 g of lithium chloride and 5.85 g of sodium azide and 8.2 g of triethylammonium bromide in 100 ml of DMF were heated at 120° C. for 8 h in a 250 ml round-bottom flask fitted with a reflux condenser. After cooling to room temperature, 100 ml of water were added, and, in an ice bath, dilute hydrochloric acid was added until no more precipitate formed. The mixture was filtered with suction, and the precipitate was washed with water and dried. Recrystallization from ethanol/water produced 4.4 g of colorless crystals.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH2:17][CH3:18])=[N:15][CH:16]=[C:10]2[CH:9]1[CH2:19][CH2:20][C:21]1[CH:26]=[C:25]([F:27])[C:24]([C:28]([F:31])([F:30])[F:29])=[CH:23][C:22]=1[F:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:33]N1C(=O)CCC1=O>CC#N.CC(=O)OCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH2:17][CH3:18])=[N:15][C:16]([Cl:33])=[C:10]2[CH:9]1[CH2:19][CH2:20][C:21]1[CH:26]=[C:25]([F:27])[C:24]([C:28]([F:30])([F:31])[F:29])=[CH:23][C:22]=1[F:32])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCc1ncc2n1CCN(C(=O)OC(C)(C)C)C2CCc1cc(F)c(C(F)(F)F)cc1F
Reactant: O=C1CCC(=O)N1Cl
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCc1nc(Cl)c2n1CCN(C(=O)OC(C)(C)C)C2CCc1cc(F)c(C(F)(F)F)cc1F
Temperature: 70 °C

Procedure:
To a yellow homogeneous solution of 8-[2-(2,5-difluoro-4-trifluoromethyl-phenyl)-ethyl]-3-ethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (1.400 g; 3.047 mmol) in anhydrous MeCN (50 ml) was added dropwise, at rt, a solution of N-chlorosuccinimide (0.407 g; 3.047 mmol; 1 eq.) in anhydrous MeCN (25 ml). The resulting solution was then heated to 70° C., under nitrogen, for 3 h30. Concentration to dryness afforded a yellow oily residue which was dissolved in EA (150 ml), and this organic layer was successively washed with aq. sat. NaHCO3 (2×50 ml), and brine (50 ml), and was then dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=50/1) gave the expected 1-chloro-8-[2-(2,5-difluoro-4-trifluoromethyl-phenyl)-ethyl]-3-ethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester as a yellow solid (0.711 g; 47%). LC-MS: tR=1.10 min.; [M+H]+=493.93 g/mol.
Reaction SMILES: NC1C([N+]([O-])=O)=CN=C(Cl)C=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:39])[CH2:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[C:33]([NH2:35])[C:32]([N+:36]([O-])=O)=[CH:31][N:30]=3)[CH2:25][CH2:24]2)=[CH:15][CH:14]=1>C(OCC)(=O)C>[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:39])[CH2:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[C:33]([NH2:35])[C:32]([NH2:36])=[CH:31][N:30]=3)[CH2:25][CH2:24]2)=[CH:15][CH:14]=1
Reactant: Nc1cc(N2CCN(CCCC(=O)c3ccc(F)cc3)CC2)ncc1[N+](=O)[O-]
Agent: Nc1cc(Cl)ncc1[N+](=O)[O-]
Solvent: CCOC(C)=O
Product: Nc1cnc(N2CCN(CCCC(=O)c3ccc(F)cc3)CC2)cc1N

Procedure:
The starting material may be prepared as described in Example 1 starting from 4-amino-2-chloro-5-nitro-pyridine via 1-(4-fluorophenyl)-4-[4-(4-amino-5-nitro-pyridin-2-yl)-1-piperazinyl]-1-butanone to give 1-(4-fluorophenyl)-4-[4-(4,5-diamino-pyridin-2-yl)-1-piperazinyl]-1-butanone, m.p. 166°-169° (from ethyl acetate).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5](F)=[CH:4][C:3]=1[CH3:12].[NH2:13][CH2:14][C:15]([O-:17])=[O:16].[Na+:18]>CN(C=O)C.O>[Na+:18].[Br:1][C:2]1[C:3]([CH3:12])=[CH:4][C:5]([NH:13][CH2:14][C:15]([O-:17])=[O:16])=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1
Reactant: Cc1cc(F)c([N+](=O)[O-])cc1Br
Reactant: NCC(=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc(NCC(=O)[O-])c([N+](=O)[O-])cc1Br
Temperature: 70 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 2-bromo-5-fluoro-4-nitrotoluene (1.662 g, 7.102 mmol, as prepared above) in DMF (7.0 mL) at 70° C., was added, dropwise, a solution of sodium glycinate (0.690 g, 7.11 mmol, Aldrich, used as received) in water (7.0 mL). The resulting suspension was stirred overnight at 70° C. The suspension was cooled to room temperature and the red solid was filtered, washed with acetone, and dried under vacuum to give 0.932 g (45%) of the pure (1H NMR) title compound as a red powder; 1H NMR (DMSO-d6): δ2.306 (s, 3H), 3.452 (d, 2H, J=3.9 Hz), 6.874 (s, 1H), 8.125 (s, 1H), 8.779 (s, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:31])[N:5]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[N:9]([C:20](Cl)=[O:21])[CH:8]([CH3:23])[CH2:7]1)[CH3:2].[F:32][C:33]([F:37])([F:36])[CH2:34][OH:35].[H-].[Na+]>O1CCOCC1>[F:32][C:33]([F:37])([F:36])[CH2:34][O:35][C:20]([N:9]1[C:10]2[C:15](=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=2)[C@H:6]([N:5]([CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:4]([O:3][CH2:1][CH3:2])=[O:31])[CH2:7][C@@H:8]1[CH3:23])=[O:21]
Reactant: OCC(F)(F)F
Reactant: CCOC(=O)N(Cc1ccccc1)C1CC(C)N(C(=O)Cl)c2cc(OC)c(OC)cc21
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CCOC(=O)N(Cc1ccccc1)[C@@H]1C[C@H](C)N(C(=O)OCC(F)(F)F)c2cc(OC)c(OC)cc21
Yield: 156 %

Procedure:
A solution of benzyl-(1-chlorocarbonyl-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-carbamic acid ethyl ester (Example 107A) (24 mg, 0.054 mmol), 2,2,2-trifluoroethanol (0.10 mL, 1.4 mmol), and sodium hydride (56 mg, 60% dispersion in mineral oil, 1.4 mmol) in anhydrous dioxane (1 mL) was stirred at room temperature overnight. The reaction mixture was quenched with 10 mL of water and extracted with ethyl acetate (3×15 mL). The combined organic phases were washed with 10 ml of brine, dried over sodium sulfate, filtered and concentrated in vacuo to give 43 mg of an oil. Purification by silica gel chromatography using 0-50% ethyl acetate/hexanes as eluent afforded the desired final product (15 mg, 58%): MS m/z 510 (M+), 528 (M++18); 1H NMR (CDCl3) δ6.99 (C8, s, 1H), 6.44 (C5, s, 1H).
Reaction SMILES: O[C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.[Na].N#N.C1OC1CO.Cl>CS(C)=O.OCC(CO)O>[C:8]([OH:10])(=[O:9])[CH:7]=[CH:6][C:5]1[CH:4]=[CH:3][CH:2]=[CH:12][CH:11]=1
Reactant: O=C(O)C=Cc1ccc(O)cc1
Agent: Cl
Agent: N#N
Agent: OCC1CO1
Solvent: OCC(O)CO
Solvent: CS(C)=O
Product: O=C(O)C=Cc1ccccc1
Reaction time: 1 h

Procedure:
2.8 g of p-hydroxy cinnamic acid was dissolved in 3 ml of DMSO, and 10 mg of sodium was added. The mixture was stirred and heated to 90° C. under a flow of N2 gas. 5.0 g of glycidol was added gradually, the heating and agitation was carried out for 1 hours, neutralized by adding hydrochloric acid and then the adduct of cinnamic acid and glycerin was obtained.
Reaction SMILES: [Br-:1].[C:2]1([CH2:28][N+:29]2([CH2:41][C:42]3C=CC=C[CH:43]=3)[CH:34]=[CH:33][C:32]([C:35]3[CH:40]=[CH:39][NH+:38]=[CH:37][CH:36]=3)=[CH:31][CH2:30]2)[CH:7]=[CH:6][C:5]([CH2:8][N+:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][N+:18]([CH2:21][C:22]4C=CC=C[CH:23]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[Br-].[Br-].[Br-].C([Br:54])C=C>>[Br-:54].[C:2]1([CH2:28][N+:29]2([CH2:41][CH:42]=[CH2:43])[CH:30]=[CH:31][C:32]([C:35]3[CH:36]=[CH:37][NH+:38]=[CH:39][CH:40]=3)=[CH:33][CH2:34]2)[CH:7]=[CH:6][C:5]([CH2:8][N+:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:16]=[CH:17][N+:18]([CH2:21][CH:22]=[CH2:23])=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[Br-:1].[Br-:54].[Br-:54]
Reactant: C1=C[N+](Cc2ccccc2)(Cc2ccc(C[n+]3ccc(-c4cc[n+](Cc5ccccc5)cc4)cc3)cc2)CC=C1c1cc[nH+]cc1
Reactant: C=CCBr
Agent: [Br-]
Product: C=CC[n+]1ccc(-c2cc[n+](Cc3ccc(C[N+]4(CC=C)C=CC(c5cc[nH+]cc5)=CC4)cc3)cc2)cc1

Procedure:
Compound 15 was synthesized as described above for compound 14, reflux time 3 h. Allyl bromide (1.97 g, 16.28 mmol), compound 4 (1.0 g, 1.42 mmol). The target compound was isolated as a bright yellow solid. Yield: 0.48 g, 42%. 1H NMR (D2O, 400 MHz): δ (ppm) 9.21-9.23 (4H, d), 9.14-9.16 (4H, d), 8.601 (8H, m), 7.68 (4H, s), 6.19-6.26 (2H, m), 6.03 (4H, s), 5.57-5.67 (2H, quad), 5.37-5.39 (2H, d). 13C NMR (D2O, 100 MHz): δ (ppm) 153.48, 153.04, 148.70, 148.66, 148.65, 148.63, 148.52, 148.46, 148.38, 136.95, 133.21, 132.33, 130.13, 129.89, 126.60, 67.01, 66.54.
Reaction SMILES: [CH2:1]1[O:6][CH:2]1[CH2:3][CH2:4][CH3:5].[CH2:7]([NH2:20])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][NH2:19]>>[CH2:18]([NH:19][CH2:1][CH:2]([OH:6])[CH2:3][CH2:4][CH3:5])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][NH:20][CH2:1][CH:2]([OH:6])[CH2:3][CH2:4][CH3:5]
Reactant: NCCCCCCCCCCCCN
Reactant: CCCC1CO1
Product: CCCC(O)CNCCCCCCCCCCCCNCC(O)CCC

Procedure:
Condensation of 1-pentene oxide and 1,12-dodecanediamine affords N,N'-(1,12-dodecylene)-bis[2-hydroxypentylamine] (I: R = CH3 (CH2)2, R' = H, X = (CH2)12, Z = H).
Reaction SMILES: O[C@@H:2]1[CH2:25][C:24]2[C@:19]([CH3:27])([CH:20]=[CH:21][C:22](=[O:26])[CH:23]=2)[C@@H:18]2[C@@H:3]1[C@H:4]1[C@:15]([CH3:28])([CH2:16][CH2:17]2)[C@@H:7]([CH:8]([CH3:14])[CH:9]([O:12][CH3:13])[O:10][CH3:11])[CH2:6][CH2:5]1.CC1(C)COC(C([C@@H]2[C@]3(C)[C@H]([C@H]4[C@H](CC3)[C@]3(C)C(=CC(=O)C=C3)C[C@H]4O)CC2)C)OC1>>[CH3:13][O:12][CH:9]([O:10][CH3:11])[CH:8]([CH3:14])[C@@H:7]1[C@:15]2([CH3:28])[C@H:4]([C@H:3]3[C@H:18]([CH2:17][CH2:16]2)[C@:19]2([CH3:27])[C:24](=[CH:23][C:22](=[O:26])[CH:21]=[CH:20]2)[CH:25]=[CH:2]3)[CH2:5][CH2:6]1
Reactant: COC(OC)C(C)[C@H]1CC[C@H]2[C@@H]3[C@H](O)CC4=CC(=O)C=C[C@]4(C)[C@H]3CC[C@]12C
Agent: CC(C1OCC(C)(C)CO1)[C@H]1CC[C@H]2[C@@H]3[C@H](O)CC4=CC(=O)C=C[C@]4(C)[C@H]3CC[C@]12C
Product: COC(OC)C(C)[C@H]1CC[C@H]2[C@@H]3C=CC4=CC(=O)C=C[C@]4(C)[C@H]3CC[C@]12C
Yield: 83.8 %

Procedure:
The procedure of Example 5 was repeated except that 2.50 g (6.44 mmoles) of 7α-hydroxy-21,21-dimethoxy-20-methylpregna-1,4-dien-3-one was used in lieu of 3.00 g of 20-(5,5-dimethyl-1,3-dioxan-2-yl)-7α-hydroxypregna-1,4-dien-3-one to give 2.00 g of 21,21-dimethoxy-20-methylpregna-1,4,6-trien-3-one (yield: 84%).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)=[O:7].[I-:19].[Na+].CCCCCC>CC(C)=O>[I:19][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)=[O:7]
Reactant: [I-]
Reactant: O=C(CCCCCl)Nc1ccc(C(F)(F)F)cc1
Agent: [Na+]
Solvent: CCCCCC
Solvent: CC(C)=O
Product: O=C(CCCCI)Nc1ccc(C(F)(F)F)cc1

Procedure:
5--Chloro-N-[4--(trifluoromethyl)phenyl]-pentanamide (2.795 g) and sodium iodide (3.32 g) were stirred in acetone (20 ml) at 22° C. for 3d, then heated at reflux for 16h, all under nitrogen. The cooled reaction mixture was chromatographed with 50:50 ethyl acetate:hexane to isolate product with Rf =0.30 in 35:65 ethyl acetate:hexane by addition of hexane and evaporation of solvent under a stream of nitrogen afforded, after suction filtration, a white solid (2.8 87 g). The product iodide contained ca. 5% starting chloride and was used without further purification.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@H:6]2[O:12][C:13]1[CH:26]=[CH:25][C:16]2[C@H:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:18][O:19][C:15]=2[CH:14]=1.[CH3:27][C:28]1[CH:33]=[C:32]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:40])=[O:39])[CH:31]=[C:30]([CH3:42])[C:29]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:42][C:30]1[CH:31]=[C:32]([O:34][CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:39])=[O:40])[CH:33]=[C:28]([CH3:27])[C:29]=1[C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@H:6]2[O:12][C:13]1[CH:26]=[CH:25][C:16]2[C@H:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:18][O:19][C:15]=2[CH:14]=1
Reactant: Cc1cc(OCCCS(C)(=O)=O)cc(C)c1B1OC(C)(C)C(C)(C)O1
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(Br)ccc(F)c43)ccc21
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(-c5c(C)cc(OCCCS(C)(=O)=O)cc5C)ccc(F)c43)ccc21
Temperature: 120 °C
Yield: 20.3 %

Procedure:
Methyl 2-((S)-6-((R)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate [intermediate 1, step 3] (32 mg), 2-(2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (42 mg), [1,1′-bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (6 mg), 1,1′-bis(diphenylphosphino)-ferrocene (4 mg) and caesium carbonate (50 mg) are suspended in toluene (2 mL) and degassed for 5 minutes with a flow of nitrogen. The mixture is heated under microwave irradiation for 90 minutes at 120° C. The mixture is diluted with ethyl acetate, washed with water, the organic phase dried and the solvent removed under vacuum. The residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 100:0→50:50) to give the title compound (9 mg). LC (method 19): tR=1.38 min; Mass spectrum: m/z=583 [M+H]+.