Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl.FC(F)(F)S(O[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C@:31]2([OH:48])[C:38]3[N:34]([CH:35]=[N:36][CH:37]=3)[C@@H:33]([C:39]3[CH:44]=[CH:43][C:42]([C:45]#[N:46])=[CH:41][C:40]=3[F:47])[CH2:32]2)[CH:26]=1)(=O)=O>COCCOC.[Pd].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.[Fe+2]>[F:47][C:40]1[CH:41]=[C:42]([CH:43]=[CH:44][C:39]=1[C@@H:33]1[N:34]2[CH:35]=[N:36][CH:37]=[C:38]2[C@@:31]([OH:48])([C:27]2[CH:26]=[CH:25][CH:30]=[C:29]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH:28]=2)[CH2:32]1)[C:45]#[N:46]
Reactant: OB(O)c1cccnc1
Reactant: N#Cc1ccc([C@H]2C[C@](O)(c3cccc(OS(=O)(=O)C(F)(F)F)c3)c3cncn32)c(F)c1
Agent: [Fe+2]
Agent: [Pd]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Solvent: ClCCl
Product: N#Cc1ccc([C@H]2C[C@](O)(c3cccc(-c4cccnc4)c3)c3cncn32)c(F)c1
Temperature: 120 °C
Yield: 48.1 %

Procedure:
To a conical microwave vial was added pyridin-3-ylboronic acid (16 mg, 0.13 mmol), sodium carbonate (18 mg, 0.17 mmol), Pd.dppf.CH2Cl2 (7.0 mg, 0.009 mmol) followed by the addition of a solution of 3-((5R,7S)-5-(4-cyano-2-fluorophenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)phenyl trifluoromethanesulfonate (20 mg, 0.043 mmol) in DME (2 mL). To this crude was added 0.5 ml distilled water. The reaction was carried out under sealed-vessel microwave heating at 120° C. for 10 min using a Biotage Initiator™ (pre-stirring: 60 s, absorption level: very high). Upon completion of the reaction, the mixture was allowed to cool to room temperature, the Pd catalyst was filtered off with a plug of silica using a monster pipet. The solvent was removed. The crude was concentrated and then purified via HPLC, using 10-90% MeCN/H2O to give 8.2 mg of the entitled product. MS 397.1 (M+H); LCMS condition A, retention time 0.92 min. 1H NMR (400 MHz, CDCl3) δ ppm 2.99 (d, 1H), 3.35 (dd, 1H), 5.77 (d, 1H), 6.83 (s, 1H), 7.10-7.22 (m, 1H), 7.23-7.50 (m, 7H), 7.72-7.84 (m, 2H), 8.36-8.49 (m, 1H), 8.59 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].C([O:15][C@@H:16]1[C@@H:29]([O:30]C(=O)C)[C@H:28]([O:34]C(=O)C)[CH2:27][S:26][C@H:17]1[O:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23](Br)[CH:24]=1)(=O)C>>[O:18]([C:19]1[CH:20]=[N:21][CH:22]=[C:23]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=2)[CH:24]=1)[C@@H:17]1[S:26][CH2:27][C@@H:28]([OH:34])[C@H:29]([OH:30])[C@H:16]1[OH:15]
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(Br)c1
Reactant: OB(O)c1ccc(F)c(Cl)c1
Product: O[C@@H]1[C@@H](O)[C@H](Oc2cncc(-c3ccc(F)c(Cl)c3)c2)SC[C@H]1O

Procedure:
By following a procedure analogous to Example 122 starting from 3-chloro-4-fluorophenylboronic acid and 5-bromo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside, 5-(3-chloro-4-fluorophenyl)-3-pyridinyl 5-thio-β-D-xylopyranoside is obtained in the form of a white powder (yield=59%).
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:39])[C:10]1[CH:15]=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[C:12]([CH2:25][N:26]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]([CH:29]2[CH2:31][CH2:30]2)=[O:28])[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:40]([O:42][C:43](=[O:52])[CH2:44][C:45]1[CH:46]=[N:47][CH:48]=[C:49](Br)[CH:50]=1)[CH3:41]>>[CH2:40]([O:42][C:43](=[O:52])[CH2:44][C:45]1[CH:46]=[N:47][CH:48]=[C:49]([C:13]2[CH:14]=[CH:15][C:10]([C:9](=[O:39])[NH:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:11][C:12]=2[CH2:25][N:26]([CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:27]([CH:29]2[CH2:31][CH2:30]2)=[O:28])[CH:50]=1)[CH3:41]
Reactant: CC1(C)OB(c2ccc(C(=O)NCc3ccccc3)cc2CN(Cc2ccccc2)C(=O)C2CC2)OC1(C)C
Reactant: CCOC(=O)Cc1cncc(Br)c1
Product: CCOC(=O)Cc1cncc(-c2ccc(C(=O)NCc3ccccc3)cc2CN(Cc2ccccc2)C(=O)C2CC2)c1

Procedure:
N-Benzyl-3-[(N-benzyl-N-cyclopropanecarbonyl-amino)-methyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide and (5-bromo-pyridin-3-yl)-acetic acid ethyl ester were reacted as described in Example 3, Step 6 to provide (5-{4-benzylcarbamoyl-2-[(N-benzyl-N-cyclopropanecarbonyl-amino)-methyl]-phenyl}-pyridin-3-yl)-acetic acid ethyl ester.
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].IC.[F:9][C:10]1[CH:20]=[CH:19][C:13]([CH:14]([OH:18])[C:15]([OH:17])=[O:16])=[CH:12][CH:11]=1>CN(C)C=O.O.C(OCC)(=O)C>[F:9][C:10]1[CH:20]=[CH:19][C:13]([CH:14]([OH:18])[C:15]([O:17][CH3:1])=[O:16])=[CH:12][CH:11]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(O)C(O)c1ccc(F)cc1
Agent: [K+]
Solvent: CI
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)C(O)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 87.3 %

Procedure:
Add potassium carbonate (12 g, 87 mmol) followed by iodomethane (7.37 mL, 118 mmol) to a 0° C. solution of p-fluoromandelic acid (79 mmol, 13.4 g) in 160 mL dry dimethylformamide under a nitrogen atmosphere. Stir the resulting mixture at 0° C. for 1 hour and at room temperature over night. Pour the reaction mixture over ice, dilute with water and ethyl acetate, and extract the aqueous layer three times with ethyl acetate. Wash the combined organic layers with cold water and saturated aqueous sodium chloride, dry over sodium sulfate and concentrate under reduced pressure to provide 12.7 g (87%) of the desired compound as a light yellow oil.
Reaction SMILES: Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([C:21]4[CH:26]=[C:25]([CH:27]([F:29])[F:28])[CH:24]=[CH:23][C:22]=4[O:30][CH2:31][CH:32]4[CH2:34][CH2:33]4)[C:15]=3[NH:14][C:13]=2[CH3:35])=[O:11])[CH2:5][CH2:4]1.[CH3:36][O:37][CH2:38][C:39](Cl)=[O:40]>>[CH:32]1([CH2:31][O:30][C:22]2[CH:23]=[CH:24][C:25]([CH:27]([F:29])[F:28])=[CH:26][C:21]=2[C:20]2[C:15]3[NH:14][C:13]([CH3:35])=[C:12]([C:10]([NH:9][C@H:6]4[CH2:7][CH2:8][C@H:3]([NH:2][C:39](=[O:40])[CH2:38][O:37][CH3:36])[CH2:4][CH2:5]4)=[O:11])[C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:34][CH2:33]1
Reactant: COCC(=O)Cl
Reactant: Cc1[nH]c2c(-c3cc(C(F)F)ccc3OCC3CC3)ncnc2c1C(=O)N[C@H]1CC[C@H](N)CC1
Agent: Cl
Product: COCC(=O)N[C@H]1CC[C@H](NC(=O)c2c(C)[nH]c3c(-c4cc(C(F)F)ccc4OCC4CC4)ncnc23)CC1

Procedure:
Starting from N-(trans-4-aminocyclohexyl)-4-[2-(cyclopropylmethoxy)-5-(difluoromethyl)phenyl]-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-7-carboxamide hydrochloride (example D.f61) and commercially available methoxy-acetyl chloride the title compound is obtained as colorless solid.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][CH2:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)([CH3:13])[CH3:12])=[N:7][CH:8]=1.CCN(C(C)C)C(C)C.C(Cl)Cl.[C:33](=[O:37])([O:35][CH3:36])N>O>[F:20][C:17]1[CH:16]=[CH:15][C:14]([C:11]([CH3:13])([CH3:12])[CH2:10][NH:9][C:6]2[N:7]=[CH:8][C:3]([CH2:2][NH:1][C:33](=[O:37])[O:35][CH3:36])=[CH:4][CH:5]=2)=[CH:19][CH:18]=1
Reactant: CC(C)(CNc1ccc(CN)cn1)c1ccc(F)cc1
Reactant: COC(N)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: COC(=O)NCc1ccc(NCC(C)(C)c2ccc(F)cc2)nc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 16.3 %

Procedure:
To a 20 dram vial was added 5-(aminomethyl)-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridin-2-amine (100 mg, 0.37 mmol, 1.0 equiv), DIPEA (57 mg, 0.44 mmol, 1.2 equiv) and CH2Cl2 (1.2 mL). The mixture was cooled to 0° C., and methyl carbamate (35 mg, 0.4 mmol, 1.0 equiv) was then added. The reaction was allowed to warm to rt and stirred for 2 h. The reaction mixture was then diluted with water (2 mL) and extracted with ethyl acetate (15 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography, affording 20 mg of methyl (6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridin-3-yl)methylcarbamate (m/z [M+H]=332).
Reaction SMILES: Cl[C:2]1[C:7]([S:8]([NH:11][CH3:12])(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(N(CC)C(C)C)(C)C>>[CH3:12][NH:11][S:8]([C:7]1[C:2]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[N:3][CH:4]=[CH:5][CH:6]=1)(=[O:10])=[O:9]
Reactant: C1CNCCN1
Reactant: CNS(=O)(=O)c1cccnc1Cl
Solvent: CCN(C(C)C)C(C)C
Product: CNS(=O)(=O)c1cccnc1N1CCNCC1

Procedure:
A mixture of 2-chloro-N-methyl-3-pyridinesulfonamide (1 g, 4.8 mmol, Specs), piperazine (0.43 g, 5 mmol) and N,N-diisopropylethylamine (1 mL, 5.8 mmol, Aldrich) was reacted under the conditions of Example 41a to give the title compound as a white amorphous solid. MS (ESI, pos. ion) m/z: 257 (M+1).
Reaction SMILES: [F:1][CH:2]([F:20])[O:3][C:4]1[C:9]2[O:10][C:11]3[CH:16]=[CH:15][N+:14]([O-])=[CH:13][C:12]=3[C:8]=2[C:7]([CH:18]=[O:19])=[CH:6][CH:5]=1>C(O)(=O)C.ClCCl.[Fe]>[F:20][CH:2]([F:1])[O:3][C:4]1[C:9]2[O:10][C:11]3[CH:16]=[CH:15][N:14]=[CH:13][C:12]=3[C:8]=2[C:7]([CH:18]=[O:19])=[CH:6][CH:5]=1
Reactant: O=Cc1ccc(OC(F)F)c2oc3cc[n+]([O-])cc3c12
Agent: [Fe]
Solvent: ClCCl
Solvent: CC(=O)O
Product: O=Cc1ccc(OC(F)F)c2oc3ccncc3c12
Yield: 65 %

Procedure:
To a well stirred suspension of 6-(difluoromethoxy)[1]benzofuro[3,2-c]pyridine-9-carbaldehyde 2-oxide (1.0 g, 3.6 mmol) in acetic acid (15 mL) was added iron powder (800 mg, 14.28 mmol) and the mixture was stirred at about 60° C. for about 15-30 minutes. Excess acetic acid was removed under reduced pressure. The residue obtained was diluted with dichloromethane (50 mL) and filtered through a celite bed and the filtrate was washed with water (3×25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified through a silica gel column using ethyl acetate in dichloromethane as an eluent to give 6-(difluoromethoxy)[1]benzofuro[3,2-c]pyridine-9-carbaldehyde as a white solid.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][Si](OC)(OC)OC.C=O.[C:14]1([OH:24])C2[C:18](=CC=CC=2)[CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[O:24]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[CH:3]=[CH:2][NH:1]1
Reactant: CO[Si](CCCN)(OC)OC
Reactant: Oc1cccc2ccccc12
Agent: C=O
Solvent: Cc1ccccc1
Product: C1=Cc2ccccc2ON1
Yield: 80 %

Procedure:
This compound was prepared according to the method described in previous examples using 3-aminopropyltrimethoxysilane (17.9 g, 100 mmole), paraformaldehyde (6.3 g, 210 mmole), 1-naphthol (14.4 g, 100 mmole), and toluene (200 ml). The final product was obtained as a viscous liquid. The yield was 80% of theory.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[NH:7][C:8]1([CH2:11][N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]3[CH:21]=[C:22]([C:26]([NH2:28])=[O:27])[C:23]([NH2:25])=[N:24][C:13]2=3)[CH2:10]C1)([CH3:4])([CH3:3])[CH3:2].[CH2:30]([O:37]C[C@H](NC(=O)OC(C)(C)C)CI)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.IC[C@@H](NC(=O)OC(C)(C)C)C.N(C(OC(C)(C)C)=O)[C@H](CO)COCC1C=CC=CC=1.C(OC(=O)NC1(CI)CC1)(C)(C)C>>[NH2:25][C:23]1[C:22]([C:26](=[O:27])[NH2:28])=[CH:21][C:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:12]([CH2:11][C@@H:8]([NH:7][C:6](=[O:29])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[CH2:10][O:37][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:13]=2[N:24]=1
Reactant: CC(C)(C)OC(=O)N[C@H](CI)COCc1ccccc1
Reactant: CC(C)(C)OC(=O)NC1(Cn2c3ccccc3c3cc(C(N)=O)c(N)nc32)CC1
Agent: CC(C)(C)OC(=O)NC1(CI)CC1
Agent: CC(C)(C)OC(=O)N[C@H](CO)COCc1ccccc1
Agent: C[C@@H](CI)NC(=O)OC(C)(C)C
Product: CC(C)(C)OC(=O)N[C@@H](COCc1ccccc1)Cn1c2ccccc2c2cc(C(N)=O)c(N)nc21

Procedure:
(R)-tert-butyl 1-(2-amino-3-carbamoyl-9H-pyrido[2,3-b]indol-9-yl)-3-(benzyloxy)propan-2-ylcarbamate (xvi-d) was prepared following the procedure detailed in the preparation of 63, substituting (S)-tert-butyl 1-(benzyloxy)-3-iodopropan-2-ylcarbamate (prepared as detailed in the synthesis of xxvii from commercial N-Boc-L-Ser(Bzl)-ol) for tert-butyl[1-(iodomethyl)cyclopropyl]carbamate. NH4OAc QC conditions. M+H=490.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.[CH3:13][N:14]([CH3:25])[C:15]1[CH:24]=[CH:23][C:18]([C:19]([NH:21][NH2:22])=[O:20])=[CH:17][CH:16]=1>C(O)(=O)C>[CH3:13][N:14]([CH3:25])[C:15]1[CH:16]=[CH:17][C:18]([C:19]([NH:21][N:22]=[C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([I:1])[CH:3]=3)[NH:7][C:6]2=[O:11])=[O:20])=[CH:23][CH:24]=1
Reactant: O=C1Nc2ccc(I)cc2C1=O
Reactant: CN(C)c1ccc(C(=O)NN)cc1
Solvent: CC(=O)O
Product: CN(C)c1ccc(C(=O)NN=C2C(=O)Nc3ccc(I)cc32)cc1
Temperature: 100 °C

Procedure:
Following the general method as outlined in Example 1, into a suspension of 5-iodo-1H-indole-2,3-dione in acetic acid was added 4-(dimethylamino)benzohydrazide. After stirring at 100° C., the reaction mixture was cooled to rt and a yellow solid precipitated out.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.C([Sn](CCCC)(CCCC)[C:32]([O:34][CH2:35][CH3:36])=[CH2:33])CCC>O1CCOCC1.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>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([C:32]([O:34][CH2:35][CH3:36])=[CH2:33])[CH:3]=1)=[O:15]
Reactant: Cc1cc(C)c(CNC(=O)c2cc(Br)nc3c2cnn3C(C)C)c(=O)[nH]1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: C=C(OCC)c1cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c2cnn(C(C)C)c2n1

Procedure:
A solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.1 g, 0.24 mmol) and tributyl(1-ethoxyvinyl)stannane (0.09 mL, 0.26 mmol) in 1,4-dioxane (2 mL) was purged with argon for 10 min. Then, Pd(PPh3)4 (0.014 g, 0.012 mmol) was added to it and again argon was purged through it for 10 min. The reaction mixture was refluxed for 4 h. After completion of the reaction, solvent was removed under reduced pressure to afford crude material which was as such used for next step (0.12 g).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH2:9][C:10]([OH:12])=[O:11])[CH:6]=[CH:7][CH:8]=1)#[N:2].[ClH:13].[CH2:14](O)[CH3:15]>[Pd]>[ClH:13].[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([O:12][CH2:14][CH3:15])=[O:11])[CH:6]=[CH:7][CH:8]=1
Reactant: N#Cc1cccc(CC(=O)O)c1
Reactant: CCO
Agent: [Pd]
Agent: Cl
Product: CCOC(=O)Cc1cccc(CN)c1

Procedure:
A mixture of (3-cyanophenyl)acetic acid (3 g, 18.6 mmol), 10% palladium on charcoal (300 mgs) and conc. hydrochloric acid (3 eqs, 4.6 mls, 55.8 mmol) in ethanol (100 mls) was subject to an atmosphere of hydrogenation overnight. The resulting mixture was filtered through hyflo and the catalyst washed thoroughly with ethanol. The solvent was then evaporated in vacuo to give a crunchy white solid. This was triturated with ether, filtered off and dried to afford a white solid (2.76 g). 1H-NMR (400 MHz, d4-MeOH) δ 1.24 (3H,t, J 8.0), 3.69 (2H,s), 4.11 (2H,s), 4.15 (2H,q, J 13.2 6.0), 7.17-7.20 (1H, m), 7.34-7.44 (4H, m).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6](=[O:13])[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:2].S(Cl)([Cl:18])(=O)=O.O>C(Cl)Cl>[CH2:11]([O:10][C:8](=[O:9])[CH:7]([Cl:18])[C:6](=[O:13])[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:14])[CH3:12]
Reactant: CCOC(=O)CC(=O)CC(=O)OCC
Reactant: O=S(=O)(Cl)Cl
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)CC(=O)C(Cl)C(=O)OCC
Temperature: -9 °C
Yield: 215.2 %

Procedure:
Dissolve 3-oxo-pentanedioic acid diethyl ester (1122 g, 5.327 mol) in CH2Cl2 (3 L) and cool to −9° C. To the above solution, slowly add a solution of sulfuryl chloride (374 g, 2.69 mol) in CH2Cl2 (3 L) over 3 h. Upon completion, add a second charge of sulfuryl chloride (374 g, 2.69 mol) in CH2Cl2 (3 L) over 4 h. Stir the resulting cooled solution for one hour, then warm to room temperature and stir overnight. Cool the solution in an ice bath and slowly add water (8 L). Stir for 15 min, then separate the layers. Extract the aqueous layer with additional CH2Cl2. Combine the organic phases and wash with saturated NaHCO3 (3 L). Dry and concentrate the organic solution to obtain 1370 g (105%) of the title compound as a colorless oil. Use the material as-is in the next reaction without further purification. ES/MS m/z (35Cl) 235 [M−1]−.
Reaction SMILES: [C:1]1([C:7]2[S:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8]=2[CH2:16][C:17]#[N:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+].[ClH:21]>C(Cl)(Cl)Cl>[ClH:21].[C:1]1([C:7]2[S:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8]=2[CH2:16][CH2:17][NH2:18])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: N#CCc1c(-c2ccccc2)sc2ccccc12
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: NCCc1c(-c2ccccc2)sc2ccccc12
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a suspension of 15.5 parts by weight of 2-phenylbenzo[b]thiophene-3-acetonitrile in a solution of 29.6 parts by weight of cobaltous chloride hexahydrate in 769 parts by volume of methanol-benzene (5:1) is added slowly 23.8 parts by weight of sodium borohydride at 0° C. After the addition is completed, the mixture is allowed to warm to room temperature and stirred for 72 hours. The reaction mixture is then partitioned between water and ether. The aqueous layer is separated, basified with concentrated ammonium hydroxide and extracted (3xs) with ether. The organic fractions are combined, dried and concentrated to afford crude 2-phenylbenzo[b]thiophene-3-ethanamine. This material is dissolved in chloroform and shaken with 100 parts by volume of 10% aqueous hydrochloric acid. A solid precipitates; filtration of this material affords 2-phenylbenzo[b]thiophene-3-ethanamine hydrochloride, melting at 200°-201° C. (decomposition). This compound is represented by the following stuctural formula. ##STR28##
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH:8]([OH:23])[CH2:9][C:10]([F:22])([F:21])[C:11]([F:20])([F:19])[C:12]([F:18])([F:17])[C:13]([F:16])([F:15])[F:14])[CH2:3][CH2:2]1.[C:24](OC(=O)C)(=[O:26])[CH3:25]>>[C:24]([O:23][CH:8]([CH2:9][C:10]([F:21])([F:22])[C:11]([F:19])([F:20])[C:12]([F:17])([F:18])[C:13]([F:16])([F:14])[F:15])[CH2:7][N:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)(=[O:26])[CH3:25]
Reactant: CC(=O)OC(C)=O
Reactant: OC(CN1CCOCC1)CC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Product: CC(=O)OC(CN1CCOCC1)CC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 50 °C
Reaction time: 10 h
Yield: 95.1 %

Procedure:
To 36.3 g of 1-morpholino-4,4,5,5,6,6,7,7,7-nonafluoro-2-heptanol was added 11.2 g of acetic anhydride. The mixture was stirred at 50° C. for 10 hours. This was followed by conventional aqueous work-up and purification by silica gel column chromatography. There was obtained 38.5 g of 1-morpholino-4,4,5,5,6,6,7,7,7-nonafluoro-2-heptyl acetate (yield 95%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:8](Cl)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[C:27]2[C:22](=[CH:23][C:24]([NH2:28])=[CH:25][CH:26]=2)[NH:21][N:20]=1>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:28][C:24]2[CH:23]=[C:22]3[C:27]([C:19]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=4[Cl:12])=[N:20][NH:21]3)=[CH:26][CH:25]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccc2c(-c3ccccc3Cl)n[nH]c2c1
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1
Solvent: c1ccncc1
Product: O=S(=O)(Nc1ccc2c(-c3ccccc3Cl)n[nH]c2c1)c1cccc(Cl)c1
Temperature: 120 °C
Reaction time: 1 h
Yield: 59.5 %

Procedure:
To 3-chlorobenzenesulfonyl chloride (43.4 mg, 0.205 mmol) in 1.0 mL pyridine was added 3-(2-chloro-phenyl)-1H-indazol-6-ylamine (50.0 mg, 0.205 mmol). The solution was heated to 120° C. and stirred for one hour, then cooled and concentrated under reduced pressure. The residue was chromatographed through silica gel (hexanes/EtOAc 0-30%) to give 51.0 mg of 3-Chloro-N-[3-(2-chloro-phenyl)-1H-indazol-6-yl]-benzenesulfonamide, MP=187-189° C., MS (M+H)=419.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:8]([C:11]([NH2:13])=[O:12])=[C:7]2[C:3]=1[C:4]1[CH2:17][N:16](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:15][CH2:14][C:5]=1[NH:6]2.CC1C(B2OC(C)(C)C(C)(C)O2)=CC=CC=1[N:53]1[C:62](=[O:63])[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[N:55]=[CH:54]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(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>[CH3:4][C:3]1[C:7]([N:53]2[C:62](=[O:63])[C:61]3[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=3)[N:55]=[CH:54]2)=[CH:8][CH:9]=[CH:10][C:2]=1[C:2]1[CH:10]=[CH:9][C:8]([C:11]([NH2:13])=[O:12])=[C:7]2[C:3]=1[C:4]1[CH2:17][NH:16][CH2:15][CH2:14][C:5]=1[NH:6]2
Reactant: Cc1c(B2OC(C)(C)C(C)(C)O2)cccc1-n1cnc2ccccc2c1=O
Reactant: NC(=O)c1ccc(Br)c2c3c([nH]c12)CCN(C(c1ccccc1)(c1ccccc1)c1ccccc1)C3
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: Cc1ccccc1
Solvent: CCO
Product: Cc1c(-c2ccc(C(N)=O)c3[nH]c4c(c23)CNCC4)cccc1-n1cnc2ccccc2c1=O
Temperature: 90 °C
Reaction time: 15.75 h
Yield: 114.9 %

Procedure:
Alternatively, a mixture of 9-bromo-2-trityl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-6-carboxamide (78.3 mg, 0.146 mmol), 3-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)quinazolin-4(3H)-one (52.9 mg, 0.146 mmol), and 2 M aqueous sodium carbonate (0.219 mL, 0.438 mmol) in toluene (1.2 mL) and ethanol (0.3 mL) was degassed by bubbling with argon for ca. 5-10 min (1 minute with sonication). The mixture was treated with tetrakis(triphenylphosphine)palladium (8.4 mg, 0.007 mmol) and heated at 90° C. under argon. After 15.75 h, the mixture was cooled to room temperature and concentrated under vacuum. The residue was stirred in methanol, treated with a small amount of TFA and water and the resulting mixture was sonicated until the gummy insoluble material was replaced by a flocculent precipitate. The mixture was filtered and subjected to purification by preparative HPLC. Fractions containing the desired product by LCMS were combined, treated with saturated aqueous sodium bicarbonate and concentrated under vacuum to provide an aqueous suspension. The precipitate was collected by filtration, washed with water and dried under vacuum to provide the desired product as a white solid (37.7 mg, 56% yield). LCMS (M+H+) m/z 450.2. 1H NMR (400 MHz, DMSO-d6) δ 10.83-10.93 (1 H, m), 8.19-8.41 (2 H, m), 8.03 (1 H, br. s.), 7.86-7.97 (1 H, m), 7.79 (1 H, t, J=7.3 Hz), 7.58-7.70 (2 H, m), 7.41-7.57 (2 H, m), 7.23-7.41 (2 H, m), 6.74-6.88 (1 H, m), 3.02-3.28 (2 H, m), 2.90 (2 H, br. s.), 2.71 (2 H, br. s.), 1.76 (3 H, s).
Reaction SMILES: [N+](=[CH2:3])=[N-].[OH:4][CH:5]([CH2:24][O:25][CH2:26][CH2:27][CH3:28])[CH2:6][CH2:7][CH:8]1[N:12]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])[C:11](=[O:22])[CH2:10][S:9]1=[O:23]>CCOCC>[OH:4][CH:5]([CH2:24][O:25][CH2:26][CH2:27][CH3:28])[CH2:6][CH2:7][CH:8]1[N:12]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH3:3])=[O:20])[C:11](=[O:22])[CH2:10][S:9]1=[O:23]
Reactant: C=[N+]=[N-]
Reactant: CCCOCC(O)CCC1N(CCCCCCC(=O)O)C(=O)CS1=O
Solvent: CCOCC
Product: CCCOCC(O)CCC1N(CCCCCCC(=O)OC)C(=O)CS1=O
Reaction time: 4 h

Procedure:
A solution of diazomethane (approximately 2.5 g., 0.06 mole) in ether (100 ml.) is slowly added to a solution of 7-[2-(3-hydroxy-4-propoxybutyl)-1,4-dioxo-3-thiazolidinyl]heptanoic acid (11.3 g., 0.03 mole) in ether (50 ml.) with stirring and cooling (0° to 5° C.). The resulting solution is allowed to warm to and stand up at room temperature for 4 hours. After destroying excess diazomethane with acetic acid, the reaction solution is washed with 5% sodium bicarbonate solution and water, dried over sodium sulfate, and filtered. In vacuo evaporation of the filtrate leaves the title compound as an essentially colorless, viscous oil.