Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:15]([C:16]([NH:18][CH3:19])=[O:17])=[C:14]([C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)[O:13][C:5]2=[N:6][C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10].Br[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:36].C(=O)([O-])[O-].[Cs+].[Cs+]>>[Cl:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[CH2:29][CH2:28][N:8]([C:7]1[N:6]=[C:5]2[O:13][C:14]([C:20]3[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=3)=[C:15]([C:16]([NH:18][CH3:19])=[O:17])[C:4]2=[CH:3][C:2]=1[I:1])[S:9]([CH3:12])(=[O:10])=[O:11]
Reactant: Clc1ccccc1CCBr
Reactant: CNC(=O)c1c(-c2ccc(C)cc2)oc2nc(NS(C)(=O)=O)c(I)cc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CNC(=O)c1c(-c2ccc(C)cc2)oc2nc(N(CCc3ccccc3Cl)S(C)(=O)=O)c(I)cc12
Temperature: 150 °C

Procedure:
To 5-iodo-N-methyl-6-(methylsulfonamido)-2-(p-tolyl)furo[2,3-b]pyridine-3-carboxamide (150 mg, 0.309 mmol) was added 1-(2-bromoethyl)-2-chlorobenzene (678 mg, 3.09 mmol) and CESIUM CARBONATE (101 mg, 0.309 mmol) was heated at 150° C. μwave 10 min. LCMS showed 1:1 SM/Prod and 1:2 styrene/Br. Added CESIUM CARBONATE (101 mg, 0.309 mmol) and heated additional 10 min at 150° C. μwave. Added water and extracted with EtOAc. Conc. on vac. Added ACN/water and filtered with 0.45 μPTFE filter
Reaction SMILES: [C:1](OC1C2C(=CC=C(C)C=2)N(CC)C1=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([N:27]1[C:35]2[C:30](=[CH:31][C:32]([CH3:36])=[CH:33][CH:34]=2)[C:29](=[O:37])[C:28]1=[O:38])[CH:24]([CH3:26])[CH3:25]>>[C:1]([O:37][CH:29]1[C:30]2[C:35](=[CH:34][CH:33]=[C:32]([CH3:36])[CH:31]=2)[N:27]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:28]1=[O:38])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN1C(=O)C(OC(=O)c2ccccc2)c2cc(C)ccc21
Reactant: Cc1ccc2c(c1)C(=O)C(=O)N2CC(C)C
Product: Cc1ccc2c(c1)C(OC(=O)c1ccccc1)C(=O)N2CC(C)C

Procedure:
Was made in an analogous fashion to 1-ethyl-5-methyl-2-oxoindolin-3-yl benzoate using 1-isobutyl-5-methylindoline-2,3-dione. 1H-NMR δ 8.12 (d, 2H), 7.59 (t, 1H), 7.47 (t, 2H), 7.27 (s, 1H), 7.14 (d, 1H), 6.87 (d, 1H), 6.18 (s, 1H), 3.55 (m, 2H), 2.30 (s, 3H), 2.19 (m, 1H), 1.01 (dd, 6H).
Reaction SMILES: [C:1]([O:12][CH3:13])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10].[C:14]([O:27][CH3:28])(=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]C=CCC.OCP(CO)CO>C1(C)C=CC=CC=1>[C:14]([O:27][CH3:28])(=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH:10]=[CH:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:12][CH3:13])=[O:11]
Reactant: C=CCCCCCCCC(=O)OC
Reactant: CCC=CCCCCCCCC(=O)OC
Agent: OCP(CO)CO
Solvent: Cc1ccccc1
Product: COC(=O)CCCCCCCC=CCCCCCCCC(=O)OC
Temperature: 60 °C
Reaction time: 0.29 h

Procedure:
A dibasic ester composition is produced in accordance with the exemplary procedure below, including a cross-metathesis reaction between methyl 9-decenoate (9-decenoic acid methyl ester, 9-DAME) and methyl 9-dodecenoate (9-dodecenoic acid methyl ester, 9-DDAME). A 1.0:1.0 mole ratio mixture of 9-DAME and 9-DDAME (332 g) is charged to a 1 L round bottom flask and heated to 60° C. Pressure is adjusted to 100 mg Hg with ChemGlass diaphragm vacuum pump model CG-4812-30/and J-Kem Scientific Digital Vacuum Regulator Model 200 and stirring is initiated with a magnetic stir bar. After the system stabilizes at desired conditions, 80 ppm of C-827 (as toluene solution) is added (t=0 min). At approximately 15-20 min, the reaction starts bubbling vigorously and the pressure rises to approximately 500 mm Hg. Pressure restabilizes at 100 mm Hg after approximately 5-10 more minutes. At 180 min, an additional 40 ppm of the catalyst C-827 (as toluene solution) is added. Subsequently, the catalyst is deactivated with 25 equivalents tris hydroxymethyl phosphine (THMP) to C-827 at 80° C. for 120 min, THMP. The catalyst is then removed by water extraction (5:1 oil to water). The composition is dried with MgSO4. Then, light FAME stripping is conducted at 1 mm Hg and approximately 100° C. The products from this reaction include a large fraction of 18:1 dibasic ester.
Reaction SMILES: [F:1][C:2]([F:9])([F:8])/[CH:3]=[CH:4]/[C:5](O)=[O:6].C(Cl)(=O)C(Cl)=O.[CH3:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:18]=1>ClCCl.CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]([F:9])([F:8])/[CH:3]=[CH:4]/[C:5]([N:26]1[CH2:27][CH2:28][N:23]([C:19]2[CH:18]=[C:17]([CH3:16])[CH:22]=[CH:21][N:20]=2)[CH2:24][CH2:25]1)=[O:6]
Reactant: O=C(O)/C=C/C(F)(F)F
Reactant: Cc1ccnc(N2CCNCC2)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: Cc1ccnc(N2CCN(C(=O)/C=C/C(F)(F)F)CC2)c1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
(E)-4,4,4-Trifluorobut-2-enoic acid (28 mg, 0.2 mmol) was dissolved in dichloromethane (1 ml), oxalyl chloride (20 μl, 0.2 mmol) was added and the resulting solution was stirred at room temperature for 5 minutes. This solution was added to a solution of 1-(4-methyl-2-pyridyl)piperazine (36 mg, 0.2 mmol) and TEA (42 μl, 0.3 mmol) in anhydrous DMF (0.5 ml) and the resulting mixture was stirred at room temperature for one hour. The mixture was diluted with ethyl acetate, washed with sat. sodium bicarbonate solution, brine, dried (magnesium sulfate) and concentrated under reduced pressure. The residue was used directly in the next step. MS (multi-mode) m/z=300.1 [M+1]+.
Reaction SMILES: C([O:4][CH2:5][CH2:6][N:7]([C:17]1[C:18]([I:44])=[C:19]([CH2:39][O:40]C(=O)C)[C:20]([I:38])=[C:21]([C:36]=1[I:37])[C:22]([NH:24][CH2:25][CH:26]([O:32]C(=O)C)[CH2:27][O:28]C(=O)C)=[O:23])[C:8]([CH:10]1[CH2:14][O:13]C(C)(C)[O:11]1)=[O:9])(=O)C.[OH-].[Na+].O>CO>[OH:4][CH2:5][CH2:6][N:7]([C:8](=[O:9])[CH:10]([OH:11])[CH2:14][OH:13])[C:17]1[C:18]([I:44])=[C:19]([CH2:39][OH:40])[C:20]([I:38])=[C:21]([C:36]=1[I:37])[C:22]([NH:24][CH2:25][CH:26]([OH:32])[CH2:27][OH:28])=[O:23]
Reactant: CC(=O)OCCN(C(=O)C1COC(C)(C)O1)c1c(I)c(COC(C)=O)c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c1I
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(NCC(O)CO)c1c(I)c(CO)c(I)c(N(CCO)C(=O)C(O)CO)c1I
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 76.2 %

Procedure:
5-[N′-(2-Acetoxyethyl)-2,2-dimethyl-1,3-dioxolane-4-carboxamido]-3-acetoxymethyl-N-(2,3-diacetoxypropyl)-2,4,6-triiodobenzamide (47 mg, 0.049 mmol) was dissolved in methanol (0.5 ml) and an aqueous solution of sodium hydroxide (2M, 0.25 ml) was added slowly followed by water (2 ml). After stirring at room temperature for 20 minutes, the reaction mixture was neutralized with a strongly acidic ion exchange resin. The resin was filtered off, and the filtrate acidified to pH=1 using hydrochloric acid (5M). After stirring at room temperature for 3.5 hours the reaction mixture was evaporated to dryness and the solid residue was purified by preparative HPLC giving 28 mg (76%) of product.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C@H:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:10](OC)=[O:11])=[N:6][CH:7]=1>CC(O)=O.[Rh]>[NH2:1][CH:2]1[CH2:3][CH2:4][CH:5]2[N:6]([C:10](=[O:11])[C@@H:9]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:8]2)[CH2:7]1
Reactant: COC(=O)[C@H](Cc1ccc(N)cn1)NC(=O)OC(C)(C)C
Agent: [Rh]
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N[C@H]1CC2CCC(N)CN2C1=O
Temperature: 25 °C
Reaction time: 25 h
Yield: 103.7 %

Procedure:
A solution of (S)-methyl 3-(5-aminopyridin-2-yl)-2-(tert-butoxycarbonylamino)propanoate (0.965 g, 3.27 mmol) 127.1 (prepared as described in WO2002068393) in glacial AcOH (40 mL) was treated with 5% Rh/C (0.67 g) and stirred at room temperature under a 60 psi H2 atmosphere for 25 hr. The catalyst was removed by filtration through a celite pad, rinsing with MeOH. The filtrate was concentrated to dryness and azeotroped from toluene (2×). The residue was dissolved in MeOH (50 mL) and treated with polymer-supported carbonate resin (2.5 g, 3.5 mmole/g) and stirred at room temperature for 24 hr. The resin was removed by filtration and the filtrate concentrated in vacuo to afford of tert-butyl (2S)-6-amino-3-oxooctahydroindolizin-2-ylcarbamate (0.913 g) 127.2 as a clear viscous oil that was used without further purification. LCMS (ESI) m/z: 270.2 [M+H]+.
Reaction SMILES: Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]2=[O:18])[CH2:5][CH2:4]1.Cl[C:20]1[N:25]=[CH:24][N:23]=[C:22]([C:26]([C:28]2[CH:39]=[C:38]([CH3:40])[C:31]3[N:32]([CH2:36][CH3:37])[C:33](=[O:35])[O:34][C:30]=3[CH:29]=2)=[O:27])[CH:21]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:36]([N:32]1[C:31]2[C:38]([CH3:40])=[CH:39][C:28]([C:26]([C:22]3[N:23]=[CH:24][N:25]=[C:20]([N:3]4[CH2:4][CH2:5][CH:6]([N:9]5[C:17]6[C:12](=[N:13][CH:14]=[CH:15][CH:16]=6)[NH:11][C:10]5=[O:18])[CH2:7][CH2:8]4)[CH:21]=3)=[O:27])=[CH:29][C:30]=2[O:34][C:33]1=[O:35])[CH3:37]
Reactant: CCn1c(=O)oc2cc(C(=O)c3cc(Cl)ncn3)cc(C)c21
Reactant: O=c1[nH]c2ncccc2n1C1CCNCC1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCn1c(=O)oc2cc(C(=O)c3cc(N4CCC(n5c(=O)[nH]c6ncccc65)CC4)ncn3)cc(C)c21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
47 mg (0.20 mmol) 1-piperidin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one-dihydrochloride, 50 mg (0.20 mmol) 6-(6-chloro-pyrimidine-4-carbonyl)-3-ethyl-4-methyl-3H-benzoxazol-2-one and 0.11 mL (0.64 mmol) DIPEA were combined in 2.0 mL DMF and stirred overnight at RT. The reaction mixture was purified by preparative HPLC. The fractions containing the product were combined, the organic solvent was evaporated down and the residue was neutralised with 1N aqueous sodium hydroxide solution. The precipitate formed was suction filtered, washed with water and dried.
Reaction SMILES: [Na].C(OCC)(=O)[CH2:3][C:4]([CH3:6])=[O:5].[Cl:11][C:12]1[C:22]([Cl:23])=[C:21]([C:24](=O)[CH:25]=[CH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:20]=[CH:19][C:13]=1[O:14][CH2:15][C:16]([OH:18])=[O:17]>C(O)C>[Cl:11][C:12]1[C:22]([Cl:23])=[C:21]([C:24]2[CH2:25][CH:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:6][C:4](=[O:5])[CH:3]=2)[CH:20]=[CH:19][C:13]=1[O:14][CH2:15][C:16]([OH:18])=[O:17]
Reactant: O=C(O)COc1ccc(C(=O)C=Cc2ccccc2)c(Cl)c1Cl
Reactant: CCOC(=O)CC(C)=O
Agent: [Na]
Solvent: CCO
Product: O=C(O)COc1ccc(C2=CC(=O)CC(c3ccccc3)C2)c(Cl)c1Cl

Procedure:
To a stirred solution of sodium (1.21 g, 0.0526 mole) in ethanol (150 ml) and ethyl acetoacetate (6.85 g, 0.0526 moles) was added [2,3-dichloro-4-(1-oxo-3-phenyl-2-propenyl)phenoxy]acetic acid (8.7 g, 0.0248 mole)(Step A). The reaction mixture was heated at reflux for 3 hours, then the solvent was distilled at reduced pressure. The residue was dissolved in water, extracted with ether, acidified with hydrochloric acid, extracted with methylene chloride and ethyl acetate, dried over magnesium sulfate and evaporated at reduced pressure to give [2,3-dichloro-4-(5-phenyl-3-oxo-1-cyclohexen-1-yl)phenoxy]acetic acid which melted at 197°-199° C.
Reaction SMILES: [CH2:1]1[C:6]2([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][CH:3]([OH:12])[CH2:2]1.O[C:14]1[C:15]([C:31]([F:34])([F:33])[F:32])=[C:16]2[C:21](=[CH:22][CH:23]=1)[CH:20]=[C:19]([C@:24]1([CH3:30])[CH2:28][O:27][C:26](=[O:29])[NH:25]1)[CH:18]=[CH:17]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl>[CH3:30][C@@:24]1([C:19]2[CH:18]=[CH:17][C:16]3[C:21](=[CH:22][CH:23]=[C:14]([O:12][CH:3]4[CH2:2][CH2:1][C:6]5([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]5)[CH2:5][CH2:4]4)[C:15]=3[C:31]([F:34])([F:32])[F:33])[CH:20]=2)[CH2:28][O:27][C:26](=[O:29])[NH:25]1
Reactant: C[C@@]1(c2ccc3c(C(F)(F)F)c(O)ccc3c2)COC(=O)N1
Reactant: OC1CCC2(CCCCC2)CC1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: C[C@@]1(c2ccc3c(C(F)(F)F)c(OC4CCC5(CCCCC5)CC4)ccc3c2)COC(=O)N1
Yield: 69.4 %

Procedure:
The mixture of spiro[5.5]undecan-3-ol (39.3 mg, 0.000234 mol) and (R)-4-(6-hydroxy-5-(trifluoromethyl)naphthalen-2-yl)-4-methyloxazolidin-2-one (60.6 mg, 0.000195 mol), and triphenylphosphine (61.2 mg, 0.000234 mol) in tetrahydrofuran (2 mL, 0.02 mol) was heated to reflux, and diisopropyl azodicarboxylate (0.0460 mL, 0.000234 mol) was added dropwise and was stirred and refluxed for overnight. The mixture was taken up into methylene chloride and subjected to chromatography purification with EtOAc/hexane (10:90 to 80:20) to give (4R)-4-methyl-4-(6-(spiro[5.5]undecan-3-yloxy)-5-(trifluoromethyl)naphthalen-2-yl)oxazolidin-2-one as a white solid (62.5 mg, 70%). LCMS Rf=2.45 min 462.40 ([M+1]+, 70%), 503.43 [M+42], 100%).
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[C@H:8]([N:9]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:10])[CH2:7][CH2:6][N:5]([CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH2:4]1.C1([O:33][C:34](=O)[NH:35][C:36]2[CH:41]=[C:40]([C:42]3[N:46]([CH3:47])[N:45]=[N:44][N:43]=3)[CH:39]=[C:38]([CH2:48][CH3:49])[CH:37]=2)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O>[CH2:11]([N:9]([CH3:10])[C@@H:8]1[CH2:7][CH2:6][N:5]([CH2:18][CH2:19][C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[CH2:4][C@H:3]1[CH2:2][NH:1][C:34]([NH:35][C:36]1[CH:41]=[C:40]([C:42]2[N:46]([CH3:47])[N:45]=[N:44][N:43]=2)[CH:39]=[C:38]([CH2:48][CH3:49])[CH:37]=1)=[O:33])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CCc1cc(NC(=O)Oc2ccccc2)cc(-c2nnnn2C)c1
Reactant: CN(Cc1ccccc1)[C@@H]1CCN(CCc2ccc(F)cc2)C[C@H]1CN
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCc1cc(NC(=O)NC[C@@H]2CN(CCc3ccc(F)cc3)CC[C@H]2N(C)Cc2ccccc2)cc(-c2nnnn2C)c1

Procedure:
A solution of trans-{3-aminomethyl-1-[2-(4-fluorophenyl)-ethyl]-piperidin-4-yl}-benzyl-methylamine (96 mg, 270 μmol), [3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-carbamic acid phenyl ester (87 mg, 270 μmol) and triethylamine (75 μL, 540 μmol) in N,N-dimethylformamide (2 mL) was stirred at room temperature for 20 hours. The solvent was removed under vacuum and the residue was dissolved in dichloromethane. The solution was washed with 1.0 N aqueous sodium hydroxide, then with water, and dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography, eluting with 4% methanol in dichloromethane containing 0.4% (112 mg, 71%). 1H NMR (300 MHz, CDCl3) δ7.68 (s, 1H), 7.39 (m, 6H), 7.20 (s, 1H), 7.15 (m, 2H), 6.97 (t, J=9 Hz, 2H), 4.14 (s, 3H), 3.80 (m, 1H), 3.7-3.4 (m, 2H), 3.3-3.1 (m, 3H), 2.82 (m, 2H), 2.7-2.5 (m, 5H), 2.29 (s, 3H), 2.1-1.6 (m, 7H), 1.20 (t, J=7 Hz, 3H). Mass spec (ES+) m/z 585.6 (M+H+).
Reaction SMILES: CS([O:5][CH2:6][CH:7]1[CH2:12][CH2:11][C:10]([F:14])([F:13])[CH2:9][CH2:8]1)(=O)=O.O[C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=[O:20].C([O-])([O-])=O.[K+].[K+].CN1C(=O)CCC1>O>[F:13][C:10]1([F:14])[CH2:11][CH2:12][CH:7]([CH2:6][O:5][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=2)[CH:19]=[O:20])[CH2:8][CH2:9]1
Reactant: CS(=O)(=O)OCC1CCC(F)(F)CC1
Reactant: O=Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=Cc1cccc(OCC2CCC(F)(F)CC2)c1
Reaction time: 1 h

Procedure:
Mesylate 142 (0.9 g, 3.94 mmole), 3-hydroxybenzaldehyde (0.577 g, 4.73 mmole), K2CO3 (0.817 g, 5.91 mmole) and NMP (5 ml) were heated at 70° C. overnight. H2O (30 ml) and hexanes (50 ml) was added and stirred for 1 hr. The organic layer was dried over Na2SO4 and evaporated. Purification by flash chromatography (20% ether/hexanes gradient) gave 3-((4,4-difluorocyclohexyl)methoxy)benzaldehyde (143) as an oil. Yield (0.559 g, 56%): 1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 7.51-7.46 (m, 2H), 7.41-7.40 (m, 1H), 7.25 (dt, J=6.8, 2.8 Hz, 1H), 3.91 (d, J=6.0 Hz, 2H), 2.06-1.98 (m, 5H), 1.89-1.73 (m, 5H), 1.37-1.27 (m, 2H).
Reaction SMILES: [C:1]([C:4]1[C:9](=[O:10])[C:8]2[CH:11]=[C:12]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:13]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])=[CH:14][C:7]=2[O:6][CH:5]=1)(=[O:3])[CH3:2].[Br:27]Br>>[Br:27][CH2:2][C:1]([C:4]1[C:9](=[O:10])[C:8]2[CH:11]=[C:12]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:13]([NH:15][S:16]([CH3:19])(=[O:17])=[O:18])=[CH:14][C:7]=2[O:6][CH:5]=1)=[O:3]
Reactant: BrBr
Reactant: CC(=O)c1coc2cc(NS(C)(=O)=O)c(Oc3ccccc3)cc2c1=O
Product: CS(=O)(=O)Nc1cc2occ(C(=O)CBr)c(=O)c2cc1Oc1ccccc1

Procedure:
3-Acetyl-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one was reacted with bromine to obtain 3-(2-bromoacetyl)-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one. It was reacted with thioformamide to obtain 7-methylsulfonylamino-6-phenoxy-3-(thiazol-4-yl)-4H-1-benzopyran-4-one.
Reaction SMILES: [S:1]1[CH:5]=[C:4]([C:6]([CH3:12])([CH3:11])[C:7]([O:9]C)=[O:8])[C:3]2[CH:13]=[CH:14][CH:15]=[CH:16][C:2]1=2.BrC1C=CC(C(C)(C)C(OCC)=O)=CC=1>>[S:1]1[CH:5]=[C:4]([C:6]([CH3:12])([CH3:11])[C:7]([OH:9])=[O:8])[C:3]2[CH:13]=[CH:14][CH:15]=[CH:16][C:2]1=2
Reactant: COC(=O)C(C)(C)c1csc2ccccc12
Agent: CCOC(=O)C(C)(C)c1ccc(Br)cc1
Product: CC(C)(C(=O)O)c1csc2ccccc12

Procedure:
The title compound was prepared according to the method of Example 22B substituting the product of Example 49B for the product of Example 22A.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11]C)=[O:10])=[C:6]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[N:5]=[C:4]([C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[N:3]=1.[OH-].[Na+]>CO>[CH3:1][C:2]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([OH:11])=[O:10])=[C:6]([C:16]2[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=2)[N:5]=[C:4]([C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[N:28]3)[N:3]=1
Reactant: CCCC(C(=O)OC)c1c(C)nc(-c2cccc3ncccc23)nc1-c1ccc(C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCC(C(=O)O)c1c(C)nc(-c2cccc3ncccc23)nc1-c1ccc(C)cc1
Yield: 25.9 %

Procedure:
This compound was prepared according to general method D from methyl 2-(4-methyl-2-(quinolin-5-yl)-6-p-tolylpyrimidin-5-yl)pentanoate (0.084 g; 0.197 mmol), sodium hydroxide 10N (0.10 mL; 1.00 mmol) in methanol (1 mL) at 60° C. for 18 h. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in water and extracted with diethyl ether. The pH of the aqueous layer was adjusted between 2 and 3 by addition of a solution of hydrochloric acid 6N until a precipitate was formed. The suspension was extracted twice with ethyl acetate and the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give 0.021 g (26%) of the title compound.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[C:3]1=[O:17].[O:18]=[C:19]1[N:28]([CH:29]2[CH2:34][CH2:33][N:32]([C:35](Cl)=[O:36])[CH2:31][CH2:30]2)[CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20]1>>[OH:16][C:13]1[CH:12]=[CH:11][C:10]([CH2:9][N:4]2[CH2:5][CH2:6][CH2:7][CH2:8][C@@H:2]([NH:1][C:35]([N:32]3[CH2:33][CH2:34][CH:29]([N:28]4[CH2:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[NH:20][C:19]4=[O:18])[CH2:30][CH2:31]3)=[O:36])[C:3]2=[O:17])=[CH:15][CH:14]=1
Reactant: N[C@@H]1CCCCN(Cc2ccc(O)cc2)C1=O
Reactant: O=C(Cl)N1CCC(N2Cc3ccccc3NC2=O)CC1
Product: O=C(N[C@@H]1CCCCN(Cc2ccc(O)cc2)C1=O)N1CCC(N2Cc3ccccc3NC2=O)CC1

Procedure:
The title compound was prepared with (3R)-3-amino-1-(4-hydroxybenzyl)azepan-2-one and 4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carbonyl chloride using a similar procedure to Example 16. MS 492.2591 (M+1).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:20])[CH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[NH:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:38])[CH2:35][CH2:36][CH3:37])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1>>[C:8]1([CH:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:6]([NH:5][CH2:4][CH2:3][CH2:2][N:21]2[CH2:26][CH2:25][CH:24]([C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:38])[CH2:35][CH2:36][CH3:37])=[CH:29][CH:28]=3)[CH2:23][CH2:22]2)=[O:20])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=C(NCCCBr)C(c1ccccc1)c1ccccc1
Reactant: CCCC(=O)Nc1ccc(C2CCNCC2)cc1
Product: CCCC(=O)Nc1ccc(C2CCN(CCCNC(=O)C(c3ccccc3)c3ccccc3)CC2)cc1

Procedure:
Example 149 was prepared from N-(3-bromopropyl)-2,2-diphenylacetamide and N-[4-(4-piperidinyl)phenyl]butanamide according to the procedures described in Scheme 14: ESMS m/e: 498.3 (M+H)+.
Reaction SMILES: C([O:5][C:6](=[O:37])[CH2:7][NH:8][C:9](=[O:36])[C:10]1[CH:15]=[CH:14][C:13]([CH:16]([CH3:34])[C:17]([OH:33])([C:22]2[CH:23]=[CH:24][C:25]3[O:29][C:28](=[O:30])[N:27]([CH3:31])[C:26]=3[CH:32]=2)[C:18]([F:21])([F:20])[F:19])=[C:12]([Cl:35])[CH:11]=1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Cl:35][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][C:13]=1[CH:16]([CH3:34])[C:17]([OH:33])([C:22]1[CH:23]=[CH:24][C:25]2[O:29][C:28](=[O:30])[N:27]([CH3:31])[C:26]=2[CH:32]=1)[C:18]([F:20])([F:21])[F:19])[C:9]([NH:8][CH2:7][C:6]([OH:37])=[O:5])=[O:36]
Reactant: CC(c1ccc(C(=O)NCC(=O)OC(C)(C)C)cc1Cl)C(O)(c1ccc2oc(=O)n(C)c2c1)C(F)(F)F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(c1ccc(C(=O)NCC(=O)O)cc1Cl)C(O)(c1ccc2oc(=O)n(C)c2c1)C(F)(F)F
Temperature: 25 °C
Reaction time: 12 h
Yield: 100.4 %

Procedure:
{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydrobenzooxazol-5-yl)-propyl]-benzoylamino}-acetic acid tert-butyl ester (20 mg, obtained in Example 231) was dissolved in dry dichloromethane (1.0 mL) and trifluoroacetic acid (0.41 mL) was added. The mixture was then allowed to stir at r.t. for 12 hours. The reaction mixture was concentrated in vacuo and the residue was further purified by repeated evaporation from ether (2 times), methanol (2 times) and again dichloromethane (2 times) to give the title compound {3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydrobenzooxazol-5-yl)-propyl]-benzoylamino}-acetic acid as a colorless solid (18 mg). MS (m/e, ISP neg. ion)=485.1 [M−H+].
Reaction SMILES: [CH3:1][O:2][CH2:3][C@@H:4]1[CH:21]2[C@:16]([CH3:23])([CH2:17][CH2:18][C:19](=O)[CH2:20]2)[C@@H:15]2[C@H:6]([C@H:7]3[C@@:11]([CH2:13][CH2:14]2)([CH3:12])[C:10](=[O:24])[CH2:9][CH2:8]3)[CH2:5]1.[ClH:25].Cl.[NH2:27][CH2:28][CH2:29][O:30][NH2:31]>>[ClH:25].[NH2:27][CH2:28][CH2:29][O:30][N:31]=[C:19]1[CH2:18][CH2:17][C@@:16]2([CH3:23])[CH:21]([C@@H:4]([CH2:3][O:2][CH3:1])[CH2:5][C@@H:6]3[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]3[CH2:8][CH2:9][C:10]2=[O:24])[CH2:20]1
Reactant: COC[C@H]1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)CCC(=O)CC12
Reactant: NCCON
Agent: Cl
Product: COC[C@H]1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)CCC(=NOCCN)CC12
Yield: 33 %

Procedure:
Prepared in 33% yield as described in Example 1 starting from 6α-methoxymethylandrostane-3,17-dione (II-ap, Prepn. 16) and 2-aminoethoxyamine dihydrochloride. The crude product was crystallized from Et2O/EtOAc. 1H-NMR (300 MHz, DMSO-d6, ppm from TMS): δ 7.82 (bb, 3H), 4.06 (m, 2H), 3.22 (m, 2H), 3.20 (s, 3H), 3.05 (m, 1H), 3.02 (m, 2H), 2.45-0.60 (m, 20H), 0.89 (s, 3H), 0.78 (s, 3H).
Reaction SMILES: [NH2:1][CH:2]([CH2:6][CH2:7][CH3:8])[C:3]([OH:5])=[O:4].C([O-])(=O)C.[Na+].CO[CH:16]1[CH2:20][CH2:19][CH:18](OC)O1>C(O)(=O)C>[N:1]1([CH:2]([CH2:6][CH2:7][CH3:8])[C:3]([OH:5])=[O:4])[CH:16]=[CH:20][CH:19]=[CH:18]1
Reactant: COC1CCC(OC)O1
Reactant: CCCC(N)C(=O)O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CCCC(C(=O)O)n1cccc1

Procedure:
2-Aminopentanoic acid (0.2 mole) is added to a solution of sodium acetate (0.2 mole) in about 300 ml of glacial acetic acid. This solution is heated to effect solution and is then refluxed for 5 minutes. To the refluxing solution is added (0.2 mole) 2.5-dimethoxytetrahydrofuran as quickly as possible. The mixture is refluxed for a further 2 minutes and the acetic acid is flash evaporated. The residue is taken up in ethyl acetate, washed with water, dried and the solvent removed under vacuo to give 2-(1-pyrryl)pentanoic acid.