Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS([N:5]1[C:9]([CH3:10])=[CH:8][C:7]([NH:11][C:12]2[N:13]=[C:14]([CH2:24]OS(C)(=O)=O)[C:15]3[C:20]([CH:21]=2)=[CH:19][C:18]([O:22][CH3:23])=[CH:17][CH:16]=3)=[N:6]1)(=O)=O.[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1>>[N:30]1([CH2:24][C:14]2[C:15]3[C:20](=[CH:19][C:18]([O:22][CH3:23])=[CH:17][CH:16]=3)[CH:21]=[C:12]([NH:11][C:7]3[CH:8]=[C:9]([CH3:10])[NH:5][N:6]=3)[N:13]=2)[CH:34]=[CH:33][N:32]=[CH:31]1
Reactant: COc1ccc2c(COS(C)(=O)=O)nc(Nc3cc(C)n(S(C)(=O)=O)n3)cc2c1
Reactant: c1c[nH]cn1
Product: COc1ccc2c(Cn3ccnc3)nc(Nc3cc(C)[nH]n3)cc2c1

Procedure:
Similar procedure as described in the example 369d was used, starting from Methanesulfonic acid 3-(1-methanesulfonyl-5-methyl-1H-pyrazol-3-ylamino)-6-methoxy-isoquinolin-1-ylmethyl ester and 1H-Imidazole to give 5 mg of (1-Imidazol-1-ylmethyl-6-methoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine as a yellow solid. LC-MS m/e 335 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:28])=[C:6]([C:8]([C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=2[NH:20][C:21](=[O:27])[CH2:22][C:23]([O:25]C)=O)=O)[CH:7]=1.CC(C)([O-])C.[K+].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:28][C:23](=[O:25])[C:22]3[C:21](=[O:27])[NH:20][C:11]4[CH:12]=[CH:13][C:14]([C:16]([F:17])([F:19])[F:18])=[CH:15][C:10]=4[C:8]=3[C:6]=2[CH:7]=1
Reactant: COC(=O)CC(=O)Nc1ccc(C(F)(F)F)cc1C(=O)c1cc(Cl)ccc1O
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: C1CCOC1
Product: O=c1[nH]c2ccc(C(F)(F)F)cc2c2c1c(=O)oc1ccc(Cl)cc12
Yield: 83 %

Procedure:
The crude 3-[[2-[(5-chloro-2-hydroxyphenyl)carbonyl]-4-(trifluoromethyl)phenyl]amino]-3-oxopropanoic acid, methyl ester prepared in Step B was dissolved in THF (15 mL) and potassium t-butoxide solution (1M in THF, 1.74 mmol, 1.74 mL) was added. The reaction mixture was heated under reflux for 15 minutes. It was then acidified with 1N HCl and the organic layer was separated. The organic layer was washed with water, brine and dried (MgSO4). Evaporation of the solvent gave a yellow solid which was triturated with ethyl acetate/hexanes to afford the title compound as a yellow solid (0.48 g, 83%): mp>250° C. MS m/e 366 (MH+).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](B(O)O)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)S(O[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([CH3:37])([CH3:36])[CH3:35])(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:34]([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[C:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:10]([S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])[CH:11]=1)([CH3:37])([CH3:36])[CH3:35]
Reactant: O=S(=O)(c1ccccc1)n1cc(B(O)O)c2ccccc21
Reactant: CC(C)(C)c1ccccc1OS(=O)(=O)C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CC(C)(C)c1ccccc1-c1cn(S(=O)(=O)c2ccccc2)c2ccccc12
Temperature: 150 °C
Yield: 90.1 %

Procedure:
1-(Phenylsulfonyl)-1H-indol-3-ylboronic acid (150.9 mg, 0.501 mmol), 2-tert-butylphenyl trifluoromethanesulfonate (255 mg, 0.902 mmol) and tetrakis(triphenylphosphine)palladium (0) (58 mg, 0.050 mmol) are combined in a septa capped microwave vial and placed under an argon atmosphere. Degassed solutions of 2 M sodium carbonate (0.75 mL, 1.50 mmol) and of dioxane (2.5 mL) were introduced and the vial heated to 150° C. for 15 minutes in a microwave reactor. The cooled reaction mixture was diluted with water and ethyl acetate, the phases separated and the aqueous extracted twice more with ethyl acetate. The combined extracts were washed with water, brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with a gradient of ethyl acetate and hexanes to give 3-(2-tert-butylphenyl)-1-(phenylsulfonyl)-1H-indole (175.8 mg, 92%) as a colorless gummy solid.
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:11]1[C:20]2[C:15](=[C:16]([F:22])[CH:17]=[CH:18][C:19]=2[F:21])[C:14]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]3[C:36]([C:37]4[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH3:44])[N:38]=4)=[CH:35][CH:34]=[CH:33][N:32]=3)=[CH:26][CH:25]=2)=[N:13][N:12]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:21][C:19]1[CH:18]=[CH:17][C:16]([F:22])=[C:15]2[C:20]=1[C:11]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[N:12][N:13]=[C:14]2[NH:23][C:24]1[CH:25]=[CH:26][C:27]([O:30][C:31]2[C:36]([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([NH:43][CH3:44])[N:38]=3)=[CH:35][CH:34]=[CH:33][N:32]=2)=[CH:28][CH:29]=1
Reactant: CNc1nccc(-c2cccnc2Oc2ccc(Nc3nnc(Cl)c4c(F)ccc(F)c34)cc2)n1
Reactant: OB(O)c1ccccc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CNc1nccc(-c2cccnc2Oc2ccc(Nc3nnc(-c4ccccc4)c4c(F)ccc(F)c34)cc2)n1
Temperature: 85 °C

Procedure:
To phenylboronic acid (0.030 g, 0.24 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.0060 g, 0.0081 mmol) and 4-chloro-5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)phthalazin-1-amine (0.080 g, 0.16 mmol) was added dioxane (0.35 mL) and sodium carbonate (2.0 M, aqueous) (0.16 ml, 0.33 mmol). The resulting mixture was heated to 85° C. in a sealed tube for 60 minutes. The reaction was diluted with EtOAc and water, and the layers were separated and the organic layers were dried over sodium sulfate, filtered and concentrated. The crude was purified by ISCO silica gel chromatography (20-100% EtOAc/hexanes; 40 g column). Concentrated product fractions to yield 5,8-difluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine as an off-white solid. MS m/z=534 [M+H]+. Calc'd for C30H21F2N7O: 533.54.
Reaction SMILES: C(OC(N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1)=O)(C)(C)C.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH:34]=[C:33]([C:36]2[CH:41]=[CH:40][C:39]([C:42]3[N:47]=[CH:46][CH:45]=[CH:44][N:43]=3)=[CH:38][C:37]=2[F:48])[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].BrC1C=C([F:56])C(Br)=CC=1F>>[C:23]([O:27][C:28]([N:30]1[CH2:31][CH:32]=[C:33]([C:36]2[CH:41]=[C:40]([F:56])[C:39]([C:42]3[N:47]=[CH:46][CH:45]=[CH:44][N:43]=3)=[CH:38][C:37]=2[F:48])[CH2:34][CH2:35]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]
Reactant: Fc1cc(Br)c(F)cc1Br
Reactant: CC(C)(C)OC(=O)N1CC=C(c2ccc(-c3ncccn3)cc2F)CC1
Agent: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Product: CC(C)(C)OC(=O)N1CC=C(c2cc(F)c(-c3ncccn3)cc2F)CC1

Procedure:
The Compound 12AQ was prepared from 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester using the procedure as described for the preparation of Compound 4-(2-fluoro-4-pyrimidin-2-yl-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester but using 1,4-dibromo-2,5-difluoro-benzene in place of 4-bromo-2-fluoro-1-iodobenzene.
Reaction SMILES: C1(O[C:8](=[O:49])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]4([C:38](=[O:47])[NH:39][C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=5[F:46])[CH2:37][CH2:36]4)=[O:34])=[C:28]([F:48])[CH:27]=3)[CH:22]=[CH:21][N:20]=2)C(OC2C=CC=CC=2)=O)C=CC=CC=1.[CH3:50][N:51]1[CH2:56][CH2:55][CH:54]([NH:57][CH3:58])[CH2:53][CH2:52]1>CN(C)C=O>[F:48][C:28]1[CH:27]=[C:26]([O:25][C:23]2[CH:22]=[CH:21][N:20]=[C:19]([NH:9][C:8]([N:57]([CH3:58])[CH:54]3[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]3)=[O:49])[CH:24]=2)[CH:31]=[CH:30][C:29]=1[NH:32][C:33]([C:35]1([C:38]([NH:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[F:46])=[O:47])[CH2:36][CH2:37]1)=[O:34]
Reactant: CNC1CCN(C)CC1
Reactant: O=C(Oc1ccccc1)N(C(=O)Oc1ccccc1)c1cc(Oc2ccc(NC(=O)C3(C(=O)Nc4ccccc4F)CC3)c(F)c2)ccn1
Solvent: CN(C)C=O
Product: CN1CCC(N(C)C(=O)Nc2cc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccccc5F)CC4)c(F)c3)ccn2)CC1
Reaction time: 8 h
Yield: 38 %

Procedure:
To a solution of [4-(3-fluoro-4-{[1-(2-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (90.6 mg) in N,N-dimethylformamide (2.0 ml) was added 1-methyl-4-(methylamino)piperidine (0.120 ml) at room temperature, followed by stirring overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous solution of ammonium chloride and brine in this order, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=98:2). Fractions containing the target compound were concentrated under reduced pressure. A solid was precipitated by addition of diethyl ether:heptane=1:1 to the resultant residue. The solid was collected by filtration. The solid was dried under aeration to provide the titled compound as white powder (30.2 mg, 38%).
Reaction SMILES: [CH2:1]([Mg]Cl)[CH2:2][CH2:3][CH3:4].[C:7]1(=[O:22])[C:20]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]=2[CH:10]=[CH:9][C:8]1=[O:21].[NH4+].[Cl-]>C1COCC1>[CH2:1]([C:8]1([OH:21])[C:7]([CH2:1][CH2:2][CH2:3][CH3:4])([OH:22])[C:20]2[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=2[C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:2][CH2:3][CH3:4]
Reactant: O=C1C=Cc2c(ccc3ccccc23)C1=O
Reactant: CCCC[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCCCC1(O)c2ccccc2-c2ccccc2C1(O)CCCC
Temperature: 25 °C
Reaction time: 6 h

Procedure:
300 ml of a 2.0 M solution of n-butylmagnesium chloride (0.6 mol) were added dropwise to a solution of 41.75 g (0.2 mol) of phenanthrenequinone in 800 ml of dry THF at an internal temperature of 10° C. over a period of 1.5 hours and the mixture was subsequently stirred at RT for 6 hours. After hydrolysis with 125 ml of saturated NH4Cl solution, the precipitate was filtered off with suction, washed with ethyl acetate, the filtrate was extracted twice with Water and the organic phase was dried over Na2SO4. The brown solid which remained after evaporation of the solvent was subsequently recrystallized twice from EtOH/H2O (70:30). This gave 60.6 g (93%) of colorless needles.
Reaction SMILES: C1C2C=CCCCC=2C=CC=1.[Cl:12][C:13]1[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=1)[C:16]([O:18]O)=[O:17]>C(Cl)Cl>[Cl:12][C:13]1[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=1)[C:16]([OH:18])=[O:17]
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: C1=Cc2ccccc2CCC1
Solvent: ClCCl
Product: O=C(O)c1cccc(Cl)c1
Reaction time: 18 h
Yield: 100 %

Procedure:
To a cold (0° C.) solution of 6,7-dihydro-5H-benzocycloheptene (0.915 g, 6.35 mmol) in methylene chloride (20 ml) was added 75% meta-chloro-peroxybenzoic acid (1.75 g, 7.63 mmol). The reaction mixture was allowed to come to room temperature over an 18 hour period. The reaction mixture was diluted with methylene chloride and washed with saturated sodium hydrogen carbonate solution, dried over MgSO4, filtered and evaporated to give the epoxide as a colorless oil (1.16 g, >100% yield, contaminated with meta-chlorobenzoic acid).
Reaction SMILES: O1CCCC1.N.[OH:7][C@@H:8]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[CH:10]([CH2:11][C:12](=[O:34])[C@@H:13]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:33])[C@H:14]3[CH2:15][CH2:16][C@@H:17]2[C@H:18]([CH3:24])[CH2:19][CH2:20][C:21]([OH:23])=[O:22])[CH2:9]1.[Li]>O.CO>[CH3:24][C@@H:18]([C@@H:17]1[C@@:25]2([CH3:33])[CH2:26][CH2:27][C@@H:28]3[C@@:29]4([CH3:32])[CH2:30][CH2:31][C@@H:8]([OH:7])[CH2:9][C@H:10]4[CH2:11][C@H:12]([OH:34])[C@H:13]3[C@@H:14]2[CH2:15][CH2:16]1)[CH2:19][CH2:20][C:21]([OH:23])=[O:22]
Reactant: C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@@H]3C(=O)CC4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: N
Agent: [Li]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@@H]3[C@@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 27 °C
Reaction time: 0.25 h
Yield: 0.1 %

Procedure:
A mixture of 9.180 liters of tetrahydrofuran and 0.460 liters of methanol at -10° C. and 7.650 liters of liquid ammonia was stirred for one hour at -35° to -40° C. and then 1.530 kg of 3α-hydroxy-7-keto-cholanic acid were added thereto over 15 minutes. 111 g of lithium were added with stirring at -35° to -38° C. over one hour to the mixture which was then stirred for one hour at -35° to -38° C. 1.530 liters of methanol were added to the mixture over 15 minutes and then 1.530 liters of demineralized water were added to the mixture over 15 minutes and stirring at 20° C. The ammonia was distilled and when the majority of the ammonia was evaporated, 7.650 liters of water were added to the mixture with stirring at 27°±2° C. Then, the tetrahydrofuran-methanol mixture was distilled off under reduced pressure at a bath temperature of 60° C. while progressively adding 1.530 liters of demineralized water to keep the volume constant and after cooling the mixture to about 27° C., 15,300 liters of water were added thereto. 7.650 liters of chloroform were added to the mixture with stirring and then 3,060 liters of 22° Be hydrochloric acid were added thereto over one hour at 27°±2° C. until a pH of 7 was obtained. At this point, acid addition was halted and the mixture was stirred for 30 minutes at 27°±2° C. after which the rest of the acid was added. The mixture was stirred for 2 hours at 27°±2° C. and was vacuum filtered with cotton cloth. The damp product was suspended in 2.300 liters of chloroform at 27°±2° C. and the suspension was stirred at 27°±2° C. for 15 minutes and was vacuum filtered. The product was resuspended in 2300 liters of chloroform at 27°±2° C. for 15 minutes and the suspension was vacuum filtered. The product was washed several times with water and dried at 60° C. to obtain 1.320 g of ursodesoxycholic acid melting at 198° C. and having a specific rotation of [α]D20 =+55.5°±0.5° (c=5% in ethanol).
Reaction SMILES: [NH2:1][CH:2]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=1)[CH2:3][OH:4].[N:12]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[N:25]=[CH:24][N:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)[N:22]=2)=[CH:17][CH:16]=1)=[C:13]=[S:14]>>[Cl:11][C:7]1[CH:6]=[C:5]([CH:2]([NH:1][C:13]([NH:12][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[N:25]=[CH:24][N:23]([C:26]4[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:33])[F:34])=[CH:28][CH:27]=4)[N:22]=3)=[CH:17][CH:16]=2)=[S:14])[CH2:3][OH:4])[CH:10]=[CH:9][CH:8]=1
Reactant: FC(F)(F)c1ccc(-n2cnc(-c3ccc(N=C=S)cc3)n2)cc1
Reactant: NC(CO)c1cccc(Cl)c1
Product: OCC(NC(=S)Nc1ccc(-c2ncn(-c3ccc(C(F)(F)F)cc3)n2)cc1)c1cccc(Cl)c1

Procedure:
The title compound was prepared with 2-amino-2-(3-chlorophenyl)ethanol and 3-(4-isothiocyanatophenyl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazole and isolated as a white solid (1.48 g, quantitative): 1H NMR (300 MHz, CDCl3) δ 8.07 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.7 Hz, 3H), 7.21 (d, J=8.5 Hz, 2H), 6.83-6.72 (m, 3H), 6.67 (d, J=7.3 Hz, 4H), 6.39 (d, J=7.9 Hz, 1H), 5.09 (s, 1H), 3.14 (dd, J=10.7, 4.4 Hz, 1H), 2.93 (dd, J=10.7, 8.0 Hz, 1H); ESIMS m/z 518 ([M+H]+).
Reaction SMILES: Cl.[C:2]([CH:7]1[CH2:16][CH2:15][C:14]2[NH:13][C:12](=[O:17])[N:11]3[CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[F:27])[N:20]=[C:10]3[C:9]=2[CH2:8]1)([O:4][CH2:5][CH3:6])=[O:3].[CH3:28]C(O)C>>[C:2]([CH:7]1[CH2:16][CH2:15][C:14]2[NH:13][C:12](=[O:17])[N:11]3[CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[F:27])[N:20]=[C:10]3[C:9]=2[CH2:8]1)([O:4][CH:5]([CH3:28])[CH3:6])=[O:3]
Reactant: CC(C)O
Reactant: CCOC(=O)C1CCc2[nH]c(=O)n3cc(-c4ccccc4F)nc3c2C1
Agent: Cl
Product: CC(C)OC(=O)C1CCc2[nH]c(=O)n3cc(-c4ccccc4F)nc3c2C1
Temperature: 150 °C

Procedure:
To 10 mL of 2-propanol saturated with HCl gas was added 9-Carboethoxy-2-(2-fluorophenyl)-7,8,9,10-tetrahydro-imidazo[1,2-c]-quinazolin-5(6H)-one (100 mg) and the mixture was heated in a sealed tube at 150° C. for 1 hour. The reaction was cooled and the solvent was evaporated in vacuo. To the reaction mixture was added 10 mL of H2O and the mixture was then brought to pH 7 with ammonium hydroxide. The solid was collected and dried to yield 9-Carboisopropoxy-2-(2-fluorophenyl)-7,8,9,10-tetrahydro-imidazo[1,2-c]quinazolin-5(6H)-one (Compound 14). m.p. 282°-285° C.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:12](Cl)(=[O:21])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CCOCC>[Br:11][C:8]1[CH:9]=[CH:10][C:2]([NH:1][C:12](=[O:21])[CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]
Reactant: O=C(Cl)CCc1ccccc1
Reactant: Nc1ccc(Br)cc1C(=O)O
Solvent: CCOCC
Product: O=C(CCc1ccccc1)Nc1ccc(Br)cc1C(=O)O
Reaction time: 8 h
Yield: 882.4 %

Procedure:
2-Amino-5-bromobenzoic acid (2.0 g, 9.3 mmol, 1.8 equiv) in ether (50 mL) was treated with hydrocinnamoyl chloride (760 uL, 0.51 mmol, 1.0 equiv) and stirred overnight. The solution was filtered and washed sparingly with ether. The filtrate, upon concentration, gave a white amorphous powder which was recrystallized from ethanol/water to give fine yellowish needles of 5-bromo-2-(3-phenylpropanamido)benzoic acid (1.58 g, 4.5 mmol, 89%). This material (1.58 g, 4.5 mmol, 1.0 equiv) was added to acetic anhydride (8 mL) and heated to 100° C. for 30 min. to dissolve all the material, then 160° C. until ca. 20% of the volume had distilled. The reaction mixture was then concentrated in vacuo to provide 6-bromo-2-phenethyl-benzo[3,1]oxazin-4-one as a yellowish waxy solid.
Reaction SMILES: [CH:1]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.C[O-].[Na+].[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]=[C:21]=[O:22])=[CH:16][CH:15]=1.Cl>O.O1CCCC1.CO>[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:9][S:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)(=[O:8])=[O:7])=[O:22])=[CH:16][CH:15]=1
Reactant: O=C=Nc1ccc(F)cc1
Reactant: NS(=O)(=O)C1CCCC1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: O=C(Nc1ccc(F)cc1)NS(=O)(=O)C1CCCC1
Yield: 20.3 %

Procedure:
The general method of procedure B was followed with cyclopentanesulfonamide (7.45 g), sodium methoxide (2.7 g), methanol (200 ml), tetrahydrofuran (200 ml), and 4-fluorophenyl isocyanate (6.85 g). The residue was dissolved in water and the solution acidified with 1N HCl. The resulting solid was separated and recrystallized from benzene to give 2.9 g of white solid with a melting point of 155-157° C.
Reaction SMILES: C[O:2][C:3](=O)[CH2:4][O:5][C:6]1[C:7]([NH2:13])=[N:8][C:9]([Br:12])=[CH:10][CH:11]=1.C([O-])([O-])=O.[K+].[K+]>CO>[Br:12][C:9]1[CH:10]=[CH:11][C:6]2[O:5][CH2:4][C:3](=[O:2])[NH:13][C:7]=2[N:8]=1
Reactant: COC(=O)COc1ccc(Br)nc1N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: O=C1COc2ccc(Br)nc2N1
Temperature: 70 °C
Reaction time: 1 h

Procedure:
(2-Amino-6-bromopyridin-3-yloxy)acetic acid methyl ester (4.0 g, 15 mmol) was dissolved in MeOH (40 mL). K2CO3 (3.0 g, 22 mmol) was added and the reaction was stirred at 70° C. for 1 hour. Then, the solvent was removed under reduced pressure and the resulting slurry was suspended in dichloromethane (DCM) and washed with H2O and then brine. The organic layer was dried (Na2SO4) and the product was precipitated from DCM/Et2O to give 6-bromo-4H-pyrido[3,2-b][1,4]oxazin-3-one. Yield 1.9 g (8.3 mmol, 55%). LCMS (ESI): calc. C7H5BrN2O2=228, 230; obs. M+H=229, 231.
Reaction SMILES: [CH3:1][N:2]([CH3:10])[CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[NH2:9].[Cl:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15](Cl)=[O:16]>>[Cl:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15]([NH:9][C@@H:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C@H:3]1[N:2]([CH3:10])[CH3:1])=[O:16]
Reactant: CN(C)C1CCCCC1N
Reactant: O=C(Cl)c1cccc(Cl)c1
Product: CN(C)[C@@H]1CCCC[C@H]1NC(=O)c1cccc(Cl)c1
Yield: 62 %

Procedure:
This titled amide was prepared by general procedure B from 2-(dimethylamino)cyclohexylamine and 3-chlorobenzoyl chloride. The crude product was crystallized from ether-petroleum ether (30°-60°); yield 62%, m.p. 112°-113°. The analytical sample melted at 112.5°-113.5°. uv sh 217 nm (ε 11,850); sh 226 (9,550); sh 277 (1,200); sh 287 (623). ir NH/=CH 3320, 3070; N-alkyl 2760; C=O 1635; C=C 1595, 1570; amide II 1545. NMR in CDCl3 (100 MHz) was in accord. Mass spectrum M+ 280.
Reaction SMILES: [C:1]([OH:12])(=O)/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].Cl.Cl.[CH2:15]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH2:15]([N:22]1[CH2:27][CH2:26][N:25]([C:1](=[O:12])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:24][CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CCCCCCC/C=C/C(=O)O
Reactant: c1ccc(CN2CCNCC2)cc1
Agent: Cl
Product: CCCCCCC/C=C/C(=O)N1CCN(Cc2ccccc2)CC1

Procedure:
The same procedures as in Example 2 were carried out using (E)-2-decenoic acid and 1-benzylpiperazine dihydrochloride as starting raw materials, to produce an intended compound.
Reaction SMILES: [C:1]([Si:5]([CH3:35])([CH3:34])[O:6][C@H:7]([C:13]1[CH:18]=[CH:17][C:16]([C:19](=C)[C@@H:20]([CH2:25][CH2:26][CH2:27][C:28]2[S:29][CH:30]=[CH:31][CH:32]=2)[CH2:21][CH2:22][CH:23]=C)=[CH:15][CH:14]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])([CH3:4])([CH3:3])[CH3:2]>Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1.C1(C)C=CC=CC=1>[C:1]([Si:5]([CH3:35])([CH3:34])[O:6][C@H:7]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C@@H:20]([CH2:25][CH2:26][CH2:27][C:28]3[S:29][CH:30]=[CH:31][CH:32]=3)[CH2:21][CH2:22][CH:23]=2)=[CH:15][CH:14]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])([CH3:3])([CH3:4])[CH3:2]
Reactant: C=CCC[C@H](CCCc1cccs1)C(=C)c1ccc([C@H](CCCCC)O[Si](C)(C)C(C)(C)C)cc1
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Solvent: Cc1ccccc1
Product: CCCCC[C@H](O[Si](C)(C)C(C)(C)C)c1ccc(C2=CCC[C@@H]2CCCc2cccs2)cc1
Yield: 94.9 %

Procedure:
A toluene (39 mL) solution of diene 40 (199 mg, 0.39 mmol) and Grubbs 2nd generation catalyst (33 mg, 0.04 mmol, Aldrich) was stirred at 50° C. for 3 h. The reaction was stored in the freezer overnight and then was evaporated and purified by flash chromatography using a Combiflash unit by Teledyne Isco (80 g silica gel, 0%→10% ethyl acetate/hexanes) to give the title compound (177 mg, 0.37 mmol, 94%).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([NH:22][C:23]3[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][N:24]=3)(=[O:21])=[O:20])=[CH:15][CH:14]=2)=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH2:30]>C(O)=O>[OH:1][C:2]1[CH:10]=[CH:9][C:8]([C:11](=[O:30])[CH2:12][C:13]2[CH:14]=[CH:15][C:16]([S:19]([NH:22][C:23]3[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][N:24]=3)(=[O:21])=[O:20])=[CH:17][CH:18]=2)=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: O
Reactant: Cc1cccnc1NS(=O)(=O)c1ccc(C#Cc2ccc(O)c(C(=O)O)c2)cc1
Solvent: O=CO
Product: Cc1cccnc1NS(=O)(=O)c1ccc(CC(=O)c2ccc(O)c(C(=O)O)c2)cc1
Yield: 71 %

Procedure:
A solution of 2-hydroxy-5-[[4-[(3-methyl-2-pyridinylamino)sulfonyl]phenyl]ethynyl]benzoic acid (4.1 g, 0.01 mol) in formic acid (100 ml) was refluxed for 30 h. Water (200 ml) was added and the product crystallized to yield 3.0 g (71%) product.