Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH:25]3[CH2:27][CH2:26]3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][NH:38][CH:37]([C:41]([N:43]([CH3:45])[CH3:44])=[O:42])[CH2:36]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:53][CH:54]([F:56])[F:55]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH:25]3[CH2:27][CH2:26]3)[CH2:16][C:17]3[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][N:38]([CH2:53][CH:54]([F:56])[F:55])[CH:37]([C:41]([N:43]([CH3:44])[CH3:45])=[O:42])[CH2:36]1
Reactant: FC(F)CBr
Reactant: COc1ccc(CN(c2nc(Nc3cc(C#N)cc(N4CCNC(C(=O)N(C)C)C4)c3Cl)nn3c(C#N)cnc23)C2CC2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(CN(c2nc(Nc3cc(C#N)cc(N4CCN(CC(F)F)C(C(=O)N(C)C)C4)c3Cl)nn3c(C#N)cnc23)C2CC2)cc1
Temperature: 80 °C
Yield: 87.9 %

Procedure:
4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-N,N-dimethylpiperazine-2-carboxamide (38 mg, 0.061 mmol, Example 563D) was taken up in DMF (0.5 mL) and Cs2CO3 (39.5 mg, 0.121 mmol) and 2-bromo-1,1-difluoroethane (5.79 μl, 0.073 mmol) were added. The reaction was heated at 80° C. for 2 h. The reaction mixture was cooled to room temperature and diluted with EtOAc. The organic layer was extracted 2× with water and once with brine, then dried over Na2SO4, filtered, and concentrated. 4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide (37 mg) was obtained as an orange glass. The crude material was taken onto the next step.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1.Br[CH2:31][CH2:32][CH:33]=[C:34]([CH3:36])[CH3:35]>>[CH3:35][C:34]([CH3:36])=[CH:33][CH2:32][CH2:31][O:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:19])[F:20])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1
Reactant: CC(C)=CCCBr
Product: CC(C)=CCCOc1cccc(-c2c(C(=O)c3ccccc3)cnc3c(C(F)(F)F)cccc23)c1

Procedure:
The title compound was prepared from [4-(3-hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl)methanone and 5-Bromo-2-methyl-pent-2-ene following the procedure of Example 478: MS (ESI) m/z 476.
Reaction SMILES: ClCCl.C([O:11][CH2:12][C:13]([NH:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[C:21]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[NH:22][C:23]2=[O:26])=[CH:18][CH:17]=1)=[O:14])C1C=CC=CC=1>[Pd].CO>[OH:11][CH2:12][C:13]([NH:15][C:16]1[CH:25]=[C:24]2[C:19]([CH:20]=[C:21]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[NH:22][C:23]2=[O:26])=[CH:18][CH:17]=1)=[O:14]
Reactant: O=C(COCc1ccccc1)Nc1ccc2cc(-c3ccccc3)[nH]c(=O)c2c1
Agent: [Pd]
Solvent: ClCCl
Solvent: CO
Product: O=C(CO)Nc1ccc2cc(-c3ccccc3)[nH]c(=O)c2c1
Reaction time: 8 h
Yield: 46 %

Procedure:
Dichloromethane was added to 5 ml of a whitish methanol solution containing the 2-benzyloxy-N-(1-oxo-3-phenyl-1,2-dihydroisoquinolin-7-yl)acetamide prepared in Example 60, until the solution became transparent. Thereafter, 10 mg of 10% Pd—C was added thereto, and the obtained mixture was then stirred under a hydrogen atmosphere for 8 hours. Thereafter, the reaction solution was filtrated with celite, and the filtrate was then concentrated, so as to obtain 7.8 mg (46%) of 2-hydroxy-N-(1-oxo-3-phenyl-1,2-dihydroisoquinolin-7-yl)acetamide in the form of a yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH3:9].C([N-]C(C)C)(C)C.[Li+].CN([CH:21]=[O:22])C.Cl>O1CCCC1.O>[Br:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5]([F:8])=[C:6]([CH:7]=1)[CH:21]=[O:22]
Reactant: Cc1cc(F)ccc1Br
Reactant: CN(C)C=O
Agent: CC(C)[N-]C(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(F)c(C=O)cc1Br
Reaction time: 2 h

Procedure:
To a solution of 2-bromo-5-fluorotoluene (20 g) in dry tetrahydrofuran (200 ml) was added dropwise lithium diisopropylamide (2.0 M, heptan-tetrohydrofuran-ethylbenzene solution, 52.9 ml) under argon atmosphere at −78° C. After stirring as such for 2 hours, a solution of DMF (41 ml) in dry tetrahydrofuran (50 ml) was added dropwise. The mixture was returned to room temperature and stirred for 1 hour. Then, water was added and the mixture was neutralized with 1N hydrochloric acid. After extraction with ethyl acetate, the extract was washed with saturated brine and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=24:1) and re-crystallized from hexane-ethyl acetate to give 5-bromo-2-fluoro-4-methylbenzaldehyde (9.39 g).