Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[CH:4][C:3]=1[CH3:25].[CH3:26][O:27][C:28]1[N:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][C:29]=1[C:30]([O:32][CH3:33])=[O:31].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:35]5[CH:36]=[N:37][C:28]([O:27][CH3:26])=[C:29]([C:30]([O:32][CH3:33])=[O:31])[CH:34]=5)[C:3]([CH3:25])=[CH:4][CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1
Reactant: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1Cl
Reactant: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)cnc1OC
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: COCCOC
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(-c2nc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)ccc2C)cnc1OC
Yield: 83.3 %

Procedure:
To N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (0.26 g, 0.7 mmol) in 1,2-dimethoxyethane (7 mL) was added methyl 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (0.25 g, 0.86 mmol), tetrakis(triphenylphosphine)palladium (0) (42 mg, 0.04 mmol), and 2 M sodium carbonate (0.70 mL, 1.4 mmol). The reaction mixture was irradiated in the microwave at 120° C. for twenty minutes. The reaction mixture was diluted with ethyl acetate (5 mL) and washed with water (5 mL). The organics were dried over sodium sulfate and evaporated to dryness. The crude reaction mixture was purified by silica gel chromatography (eluting with 0-100% ethyl acetate in hexanes) to yield the product (0.29 g, 81%). ESI-MS m/z calc. 497.45. found 498.3 (M+1)+. Retention time 2.14 minutes.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([C:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[NH:15][CH:14]=3)=[O:12])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.Br[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[N:27]=1>>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([C:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:15]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:34])([F:33])[F:35])[N:27]=4)[CH:14]=3)=[O:12])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: FC(F)(F)c1cccc(CBr)n1
Reactant: O=C(c1ccc2c(c1)OCCO2)c1c[nH]c2ccccc2c1=O
Product: O=C(c1ccc2c(c1)OCCO2)c1cn(Cc2cccc(C(F)(F)F)n2)c2ccccc2c1=O
Yield: 18.8 %

Procedure:
Experimental conditions analogous to those described for Step 3 of Example 1, from 3-(2,3-Dihydro-benzo[1,4]dioxine-6-carbonyl)-1H-quinolin-4-one 70 mg (0.228 mmol) and 71.1 mg (0.296 mmol) of 2-Bromomethyl-6-trifluoromethyl-pyridine, to give 20 mg of desired compound. LCMS (M+H)+: 467.1.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)=[O:3].N1C=CN=C1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>CN(C=O)C>[C:19]([Si:16]([CH3:18])([CH3:17])[O:10][C:7]1[CH:8]=[CH:9][C:4]([C:2](=[O:3])[CH3:1])=[CH:5][CH:6]=1)([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(=O)c1ccc(O)cc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(=O)c1ccc(O[Si](C)(C)C(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 97.8 %

Procedure:
To a solution of 4-hydroxyacetophenone (10.0 g, 73.5 mmol) in DMF (74 mL) was added imidazole (12.0 g, 176.3 mmol) and tert-butyldimethylsilyl chloride (13.3 g, 88.1 mmol). The colorless solution was stirred for 0.75 h at rt then quenched with saturated aqueous NaHCO3. The aqueous phase was extracted with hexanes and the combined organic layers were washed with saturated NaHCO3. The organic layers were dried over sodium sulfate, filtered, and concentrated to provide 1-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-ethanone (18.0 g, 98%) as a white solid which was utilized without further purification. ESI MS (m/z 251, M+H).
Reaction SMILES: [S:1]1[CH:5]=[C:4]([CH2:6][NH:7][C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:15][CH3:16])[N:3]=[CH:2]1.[Cl:17][CH2:18][C:19](Cl)=[O:20]>C1(C)C=CC=CC=1>[Cl:17][CH2:18][C:19]([N:7]([CH2:6][C:4]1[N:3]=[CH:2][S:1][CH:5]=1)[C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:15][CH3:16])=[O:20]
Reactant: CCc1cccc(C)c1NCc1cscn1
Reactant: O=C(Cl)CCl
Solvent: Cc1ccccc1
Product: CCc1cccc(C)c1N(Cc1cscn1)C(=O)CCl

Procedure:
A mixture of 3.5 g N-(thiazol-4-yl)methyl-2-ethyl-6-methylaniline (from Example 11) and 125 ml toluene was heated to reflux and 1.7 g chloroacetyl chloride was added dropwise. The mixture was refluxed for 2 hours, cooled, stripped and purified on a silica-gel column using methylene chloride followed by 2% methanol:methylene chloride. C15H17ClN2O5 : calc., %C 58.35,%H 5.51, %N, 9.08; found, %C 57.07, %H 5.58, %N 7.81.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([Mg]Br)=[CH:17][CH:16]=1.FC(F)(F)C(O)=O>O1CCCC1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2([C:18]2[CH:19]=[CH:20][C:15]([O:14][CH3:13])=[CH:16][CH:17]=2)[OH:12])=[CH:4][CH:3]=1
Reactant: O=C1CCCc2ccc(Br)cc21
Reactant: COc1ccc([Mg]Br)cc1
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(C2(O)CCCc3ccc(Br)cc32)cc1

Procedure:
A solution of 0.55 g (1.65 mmol ) of 7-bromo-1-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-ol, obtained analogously to Example 1a) from 7-bromo-3,4-dihydro-2H-naphthalen-1-one and 4-methoxyphenyl-magnesium bromide, and 0.2 ml of trifluoroacetic acid in 20 ml of tetra-hydrofuran is warmed at 50° C. for 12 hours and subsequently evaporated to dryness. 10 ml of saturated sodium hydrogencarbonate are added to the residue, and the aqueous mixture is extracted twice with 10 ml of ethyl acetate each time. After the combined organic phases have been dried over sodium sulfate and the solvent has been stripped off, the crude product is purified by column chromatography on silica gel (petroleum ether ethyl acetate 9:1), giving 0.54 g of 7-bromo-1-(4-methoxyphenyl)-3,4-dihydronaphthalene; LC/MS: 338 (M+Na).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=1)=[O:17]>>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([O:13][CH2:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=1)=[O:17])=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCCC(=O)O
Reactant: COc1cccc(C(=O)CBr)c1
Product: COc1cccc(C(=O)COC(=O)CCNC(=O)OC(C)(C)C)c1

Procedure:
The product was obtained starting from 3-(tert-butoxycarbonylamino)propanoic acid (400 mg, 2.11 mmol) and 2-bromo-1-(3-methoxyphenyl)ethanone (484 mg, 2.11 mmol) according to the method described in example 7, step 1 as yellow oil (759 mg, 2.11 mmol, 100%). MS: M=238.2 (M-Boc+H)+
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.Br[CH2:23][CH2:24][N:25]1[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[O:27][C:26]1=[O:34]>C(#N)C>[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:23][CH2:24][N:25]3[C:33]4[C:28](=[N:29][CH:30]=[CH:31][CH:32]=4)[O:27][C:26]3=[O:34])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=c1oc2ncccc2n1CCBr
Reactant: c1ccc(N2CCNCC2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=c1oc2ncccc2n1CCN1CCN(c2ccccc2)CC1

Procedure:
In a round-bottomed flask under an argon atmosphere, surmounted by a condenser, 2.43 g (15 mmol) of 1-phenylpiperazine and then 2.61 cm3 (15 mmol) of diiso-propylethylamine are added to a solution of 2.43 g (10 mmol) of 1-(2-bromoethyl)-1H-oxazolo [5,4-b]pyrdin-2-one in acetonitrile.
Reaction SMILES: O[CH2:2][CH2:3][CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[CH2:6][CH2:5]1.P(Br)(Br)[Br:16].O>ClCCl>[Br:16][CH2:2][CH2:3][CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[CH2:6][CH2:5]1
Reactant: BrP(Br)Br
Reactant: COc1ccc2c(c1)C(CCO)CC2
Solvent: ClCCl
Solvent: O
Product: COc1ccc2c(c1)C(CCBr)CC2
Reaction time: 0.5 h
Yield: 27.4 %

Procedure:
To a solution of 1-(2-hydroxyethyl)-6-methoxyindan (4.95 g, 25.7 mmol) in dichloromethane (100 ml) was added dropwise at −5° C. phosphorus tribromide (0.86 ml, 2084 27.0 mmol). The mixture was stirred for 30 minutes. To the reaction mixture was added water, which was subjected to extraction with chloroform. The extract solution was washed with brine and dried over anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The residue was purified by means of a silica gel column chromatography (hexane/ethyl acetate, 7:3→1:1) to give 1.80 g (yield 27%) of the above-titled compound as an oily product.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH:11]([NH2:15])[CH2:10]2)[CH:5]=[C:4]([I:16])[CH:3]=1.C(N(CC)CC)C.[CH:24]1([S:27](Cl)(=[O:29])=[O:28])[CH2:26][CH2:25]1>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH:11]([NH:15][S:27]([CH:24]3[CH2:26][CH2:25]3)(=[O:29])=[O:28])[CH2:10]2)[CH:5]=[C:4]([I:16])[CH:3]=1
Reactant: NC1CCCC(Nc2cc(I)cc(Cl)n2)C1
Reactant: O=S(=O)(Cl)C1CC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=S(=O)(NC1CCCC(Nc2cc(I)cc(Cl)n2)C1)C1CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 22.2 %

Procedure:
To a solution of Example 260a (0.320 g, 0.910 mmol) in DMF (6 mL) were added triethylamine (0.165 mL, 1.183 mmol) and cyclopropanesulfonyl chloride (0.102 mL, 1.001 mmol). The reaction mixture was stirred at room temperature overnight, quenched with brine and NaHCO3 and extracted with EtOAc. The organic layer was dried over MgSO4, filtered, concentrated, and purified on a 40 g column using the ISCO Companion flash system eluting with hexane/EtOAc (7:3 to 1:1) to give 0.092 g of the title compound.
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH2:6]1)=[O:4].[Cl:15][C:16]1[CH:25]=[CH:24][C:19]2[N:20]=[C:21]([SH:23])[S:22][C:18]=2[CH:17]=1>>[Cl:15][C:16]1[CH:25]=[CH:24][C:19]2[N:20]=[C:21]([S:23][CH2:2][C:3]([N:5]3[C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[CH2:8][CH2:7][CH2:6]3)=[O:4])[S:22][C:18]=2[CH:17]=1
Reactant: O=C(CCl)N1CCCc2ccccc21
Reactant: Sc1nc2ccc(Cl)cc2s1
Product: O=C(CSc1nc2ccc(Cl)cc2s1)N1CCCc2ccccc21
Yield: 73 %

Procedure:
The title compound was synthesized according to General Procedure A using compound 4 as the electrophile and 6-chlorobenzo[d]thiazole-2-thiol as the nucleophile to yield 25 as a white solid (73%): MS m/z: 375 (M+H)+. Anal. Calcd. For, C18H15ClN2OS2: C, 57.67; H, 4.03; N, 7.47; S, 17.11; Cl, 9.46. Found: C, 57.50; H, 4.05; N, 7.48; S, 16.86; Cl, 9.74.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[NH:14][C:15]([NH2:24])=[C:16]2[C:20]([N:21]=1)=[N:19][C:18]([O:22][CH3:23])=[N:17]2)[CH2:9][CH2:10][CH3:11].Br[CH2:26][CH2:27][CH2:28][CH2:29][CH:30]1[CH2:34][CH2:33][CH2:32][O:31]1>>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:26][CH2:27][CH2:28][CH2:29][CH:30]2[CH2:34][CH2:33][CH2:32][O:31]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]
Reactant: BrCCCCC1CCCO1
Reactant: CCCCOc1nc2nc(OC)nc-2c(N)[nH]1
Solvent: O=C(O)C(F)(F)F
Product: CCCCOc1nc(N)c2nc(OC)n(CCCCC3CCCO3)c2n1

Procedure:
Prepared similarly to Intermediate 213 from 2-(butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate and 2-(4-bromobutyl)tetrahydrofuran.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[N:3]=1.O.[NH2:11][NH2:12]>C(O)C>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8](=[NH:9])[NH:11][NH2:12])[N:3]=1
Reactant: Cc1ccnc(C#N)n1
Reactant: NN
Solvent: O
Solvent: CCO
Product: Cc1ccnc(C(=N)NN)n1

Procedure:
4-methyl-2-pyrimidinecarbonitrile (I98)(0.190 g, 1.595 mmol) was dissolved in ethanol (3.19 ml) and hydrazine hydrate (0.100 ml, 3.19 mmol) was added. The reaction mixture was left at reflux for 2.5 hours. TLC showed that no starting material remained so the solvent was removed under reduced pressure to afford the crude desired product in 247 mg.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:18][C:19]2[CH:24]=[C:23]([CH:25]3[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]3)[N:22]=[C:21]([NH2:31])[N:20]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[NH:15][CH:16]=[CH:17][C:10]=12.[C:32](OC(=O)C)(=[O:34])[CH3:33]>C(O)C>[C:32]([N:27]1[CH2:28][CH2:29][CH2:30][CH:25]([C:23]2[N:22]=[C:21]([NH2:31])[N:20]=[C:19]([NH:18][C:4]3[CH:5]=[CH:6][C:7]([O:8][C:9]4[CH:14]=[CH:13][N:12]=[C:11]5[NH:15][CH:16]=[CH:17][C:10]=45)=[C:2]([F:1])[CH:3]=3)[CH:24]=2)[CH2:26]1)(=[O:34])[CH3:33]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1nc(Nc2ccc(Oc3ccnc4[nH]ccc34)c(F)c2)cc(C2CCCNC2)n1
Solvent: CCO
Product: CC(=O)N1CCCC(c2cc(Nc3ccc(Oc4ccnc5[nH]ccc45)c(F)c3)nc(N)n2)C1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
50 mg (0.119 mmol) of N4-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-6-piperidin-3-ylpyrimidine-2,4-diamine (from example 134) are suspended in ethanol. 0.013 ml (0.146 mmol) of acetic anhydride are added, and the mixture is stirred at room temperature for 18 hours. The mixture is then concentrated. The residue is purified by preparative HPLC.
Reaction SMILES: Cl[C:2]1[C:3](=[O:16])[NH:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2.[NH:17]1[C:26]2[C:21](=[CH:22][C:23]([C:27]#[N:28])=[CH:24][CH:25]=2)[CH2:20][CH2:19][CH2:18]1>CN1C(=O)CCC1.O>[C:27]([C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[N:17]([C:2]1[C:3](=[O:16])[NH:4][C:5]3[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=3)[CH2:18][CH2:19][CH2:20]2)#[N:28]
Reactant: N#Cc1ccc2c(c1)CCCN2
Reactant: COC(=O)c1ccc2[nH]c(=O)c(Cl)nc2c1
Solvent: O
Solvent: CN1CCCC1=O
Product: COC(=O)c1ccc2[nH]c(=O)c(N3CCCc4cc(C#N)ccc43)nc2c1
Temperature: 150 °C
Reaction time: 1 h
Yield: 44 %

Procedure:
To a solution of methyl 3-chloro-2-oxo-1,2-dihydroquinoxaline-6-carboxylate (300 mg, 1.26 mmol) in NMP (0.5 mL) was added 1,2,3,4-tetrahydroquinoline-6-carbonitrile (597 mg, 3.77 mmol) with stirring for 1 h at 150° C. in an oil bath. The resulting solution was diluted with water (100 mL) and the solids were collected by filtration to afford methyl 3-(6-cyano-1,2,3,4-tetrahydroquinolin-1-yl)-2-oxo-1,2-dihydroquinoxaline-6-carboxylate as a yellow solid (200 mg, 44%).
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH:9]1[C:14]([C:15]([CH2:17]Br)=[O:16])=[CH:13][CH:12]=[C:11]([F:19])[CH:10]=1>C1COCC1>[F:19][C:11]1[CH:12]=[CH:13][C:14]([C:15](=[O:16])[CH2:17][NH:6][C:5]2[CH:7]=[CH:8][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:9][CH:10]=1
Reactant: Nc1ccc(F)cc1
Reactant: O=C(CBr)c1ccc(F)cc1
Solvent: C1CCOC1
Product: O=C(CNc1ccc(F)cc1)c1ccc(F)cc1
Temperature: 40 °C
Reaction time: 4 h

Procedure:
1.3 mL 4-fluoroaniline was added to 1 g 2-bromo-4-fluoroacetophenone in 20 mL THF. The reaction was stirred 3 h at RT and 4 h at 40° C. The mixture was filtered and the filtrate diluted with ethyl acetate and extracted with water. The organic layer was dried and evaporated. Diisopropylether was added to the residue. The precipitate was filtered and dried to yield 0.42 g desired product. Rt: 1.53 min (method B), (M+H)+: 248
Reaction SMILES: F[C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[C:4]([N:6]1[CH2:10][CH2:9][N:8]=[C:7]1SC)=[O:5].[NH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1>>[N:18]1([N:17]2[C:2]3[C:3](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:4](=[O:5])[N:6]3[CH2:10][CH2:9][N:8]=[C:7]23)[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: NN1CCCC1
Reactant: CSC1=NCCN1C(=O)c1ccccc1F
Product: O=C1c2ccccc2N(N2CCCC2)C2=NCCN12

Procedure:
When the procedure of Example 2 is repeated using the product of Example 1 and N-aminopyrrolidine, the product obtained is 2,10-dihydro-10-(1-pyrrolidinyl)imidazo[2,1-b]quinazolin-4(3H)-one.
Reaction SMILES: [CH3:1][C:2]1[C@@H:19]([O:20]C([C@H](O)[C@@H](NC(C2C=CC=CC=2)=O)C2C=CC=CC=2)=O)[CH2:18][C@:14]2([OH:41])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([OH:68])[C:5]([C@@:7]1([CH3:67])[C@@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[O:57][C@@H:58]1[O:63][CH2:62][C@@H:61]([OH:64])[C@H:60]([OH:65])[C@H:59]1[OH:66])=[O:6].CO.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O>[CH3:1][C:2]1[C@@H:19]([OH:20])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:16])([CH3:17])[C:3]=1[C@@H:4]([OH:68])[C:5]([C@@:7]1([CH3:67])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[O:57][C@@H:58]1[O:63][CH2:62][C@@H:61]([OH:64])[C@H:60]([OH:65])[C@H:59]1[OH:66])=[O:6]
Reactant: CC(=O)O[C@@]12CO[C@@H]1C[C@H](O[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O)[C@@]1(C)C(=O)[C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C[C@@](O)([C@@H](OC(=O)c4ccccc4)[C@@H]21)C3(C)C
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CC(=O)O[C@@]12CO[C@@H]1C[C@H](O[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O)[C@@]1(C)C(=O)[C@H](O)C3=C(C)[C@@H](O)C[C@@](O)([C@@H](OC(=O)c4ccccc4)[C@H]21)C3(C)C
Reaction time: 15 h
Yield: 103 %

Procedure:
Cells were prepared as described in Example 4. 1 mg 7-xylosyl-10-deacetyltaxol, 200 mg (108 milliunits) C-13 deacylase (described in Example 4), 0.2 ml methanol, 0.2 ml 1 M potassium phosphate buffer pH 7, and 3.6 ml water were mixed end-over-end at 48 rpm for 17 hours at 24° C. After 15 hours, HPLC analysis by Method 1 showed complete removal of C-13 side chain from the substrate. 2 ml of the solution now containing 7-xylosyl-10-deacetylbaccatin-III was added to 1 ml of the above Moraxella sp. cells (0.24 g wet cell weight) in 50 mM potassium phosphate buffer pH 7 and mixed end-over-end for 24 hours at 48 rpm. Reaction mixtures were extracted with 6 ml CH2Cl2. Extracts were dried and redissolved in methanol for HPLC analysis by Method 1. 0.099 mg/ml 10-deacetylbaccatin-III was found (103% yield based on initial 7-xylosyl-10-deacetyltaxol concentration).
Reaction SMILES: [C:1]([NH:4][C:5]1[C:6]([Cl:31])=[C:7]([NH:21][C:22](=[O:30])[C@:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])[CH:8]=[CH:9][C:10]=1[S:11]([C:14]1[CH:19]=[CH:18][C:17](F)=[CH:16][CH:15]=1)(=[O:13])=[O:12])(=[O:3])[CH3:2].[CH2:32]([CH2:34][NH2:35])[OH:33]>C(#N)C>[C:1]([NH:4][C:5]1[C:6]([Cl:31])=[C:7]([NH:21][C:22](=[O:30])[C@:23]([OH:29])([CH3:28])[C:24]([F:27])([F:25])[F:26])[CH:8]=[CH:9][C:10]=1[S:11]([C:14]1[CH:19]=[CH:18][C:17]([NH:35][CH2:34][CH2:32][OH:33])=[CH:16][CH:15]=1)(=[O:12])=[O:13])(=[O:3])[CH3:2]
Reactant: NCCO
Reactant: CC(=O)Nc1c(S(=O)(=O)c2ccc(F)cc2)ccc(NC(=O)[C@@](C)(O)C(F)(F)F)c1Cl
Solvent: CC#N
Product: CC(=O)Nc1c(S(=O)(=O)c2ccc(NCCO)cc2)ccc(NC(=O)[C@@](C)(O)C(F)(F)F)c1Cl
Temperature: 85 °C
Yield: 33.3 %

Procedure:
(R)-N-[3-Acetamido-2-chloro-4-(4-fluorophenylsulphonyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (683 mg) (Example 10), ethanolamine (177 mg, 2 eq) and acetonitrile (6 ml) were stirred and heated (85° C.) under argon for 24 hours. The solvent was removed and the residual gum was redissolved in MeOH (10 ml) and poured onto deactivated silica (5 g). This was concentrated to give a free flowing powder which was transferred to the top of an ISOLUTE column (50 g silica). This was chromatographed, eluting with MeOH/DCM to give the title compound (247 mg) as a brown solid. NMR (400 MHz): 1.59 (s, 3H), 1.95 (s, 3H), 3.08-3.19 (m, 2H), 3.53 (q, 2H), 4.66-4.73 (t, 1H), 6.62 (d, 2H), 6.67 (t, 1H), 7.0 (brs, 1H), 7.44 (d, 2H), 8.06 (d, 1H), 8.29 (d, 1H), 9.61 (brs, 1H), 9.82 (brs, 1H); m/z 524 (M+H)+.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:11]=[CH:10][C:9]2[N:8]([CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[CH3:14])[C:7]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:6]=3[C:5]=2[CH:4]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27].[OH-].[Na+]>>[CH3:1][N:2]([C:3]1[CH:11]=[CH:10][C:9]2[N:8](/[CH:12]=[C:13](/[C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)\[CH3:14])[C:7]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:6]=3[C:5]=2[CH:4]=1)[C:26](=[O:28])[CH3:27]
Reactant: CNc1ccc2c(c1)c1c(n2C=C(C)c2ccncc2)CCN(C)C1
Reactant: CC(=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Product: CC(=O)N(C)c1ccc2c(c1)c1c(n2/C=C(\C)c2ccncc2)CCN(C)C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2,3,4,5-Tetrahydro-N,2-dimethyl-5-(2-(pyridin-4-yl)prop-1-enyl)-1H-pyrido[4,3-b]indol-8-amine (23 mg) was charged in round bottom flask and acetic anhydride (0.7 mL) was added. The contents were stirred at RT for 30 min. The reaction mixture was basified with 1N NaOH and compound extracted with EtOAc (2×25 mL). The organic layer was concentrated under vacuum and recrystallized in DCM:Hexane (1:3) to yield 2.38 mg of desired compound. 1H NMR (CDCl3, free base) δ (ppm): 8.62 (d, 2H), 7.42 (d, 2H), 7.25 (s, 1H), 7.10 (dd, 2H), 6.98 (d, 1H), 3.70 (s, 2H), 3.30 (s, 3H), 2.82 (m, 4H), 3.60 (s, 3H), 2.04 (s, 3H), 1.90 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[S:21][CH:20]=[CH:19][N:5]2[C:6](=[O:18])[C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1.[CH3:22][O:23][C:24]1[C:25]([O:32][CH2:33][CH2:34][CH3:35])=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH:27]=O.[O-]CC.[Na+]>C(O)C>[CH3:22][O:23][C:24]1[C:25]([O:32][CH2:33][CH2:34][CH3:35])=[C:26](/[CH:27]=[CH:1]/[C:2]2[N:3]=[C:4]3[S:21][CH:20]=[CH:19][N:5]3[C:6](=[O:18])[C:7]=2[C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:15])[F:16])=[CH:10][CH:9]=2)[CH:29]=[CH:30][CH:31]=1
Reactant: CCCOc1c(C=O)cccc1OC
Reactant: Cc1nc2sccn2c(=O)c1-c1ccc(C(F)(F)F)cc1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCCOc1c(/C=C/c2nc3sccn3c(=O)c2-c2ccc(C(F)(F)F)cc2)cccc1OC
Yield: 49.4 %

Procedure:
The title compound was prepared by condensation of Intermediate 5 (400 mg, 1.289 mmol) with 3-methoxy-2-propoxybenzaldehyde (375 mg, 1.933 mmol) in presence of sodium ethoxide (175 mg, 2.578 mmol) in ethanol (15 ml) according to the procedure described in Example 24 to give 310 mg of the desired product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 0.93 (t, J=6.6 Hz, 3H), 1.48 (q, J=6.9 Hz, 2H), 3.77 (s, 5H), 6.93-7.00 (m, 4H), 7.52-7.59 (m, 3H), 7.82 (d, J=7.8 Hz, 2H), 7.98-8.02 (m, 2H); ESI-MS (m/z) 487.35 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]([N:16]1[CH2:23][CH2:22][CH2:21][C@H:17]1[C:18]([OH:20])=O)=[O:15])[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1CCOCC1)C.ClC(OCC(C)C)=O.[NH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>O1CCCC1.CCOCC>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]([N:16]1[CH2:23][CH2:22][CH2:21][C@H:17]1[C:18]([NH:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:20])=[O:15])[CH3:13])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccccc1
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
Agent: CC(C)COC(=O)Cl
Agent: CCN1CCOCC1
Solvent: C1CCOC1
Solvent: CCOCC
Product: C[C@H](NC(=O)OCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)Nc1ccccc1
Temperature: -10 °C
Reaction time: 0.33 h
Yield: 81 %

Procedure:
32 g (0.1 mol) of N-benzyloxycarbonyl-L-alanyl-L-proline were dissolved in 300 ml of dry tetrahydrofuran and the solution was cooled to -10° C. 12.7 ml (0.1 mol) of N-ethylmorpholine and 13.1 ml (0.1 mol) of isobutyl chloroformate were added and the solution was stirred for 20 minutes while maintaining the temperature at -10° C. 9.3 ml of aniline were then added and the mixture was stirred at 0° C. for 1 hour. The mixture was found to be slightly acidic and a further 1 g of N-ethylmorpholine was added. The solution was then left to stand at room temperature for 16 hours. The solution was evaporated, there being obtained a white crystalline solid which was treated with 500 ml of ether, filtered, washed and dried to give 31.8 g of N-benzyloxycarbonyl-L-alanyl-L-proline anilide of melting point 139.5°-140.5° C.; [α]D20 =-125.5° (c=1.195% in methanol). A second crop (1.4 g; melting point 138°-139° C.) was obtained by evaporating the mother liquor to a small volume, when crystallisation took place. The total yield was 81%.