Diisopropylethylamine → HCID 118131274, compound

HRID 634522Notes

Reaction equation

HRID 634522 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:20]([C:22]3[O:23][C:24](=[O:45])[C:25]4[C:30]([C:31]=3[C:32]3[CH2:33][N:34](CC5C=CC=CC=5)[CH2:35][CH2:36][CH:37]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:10]=[C:11]([C:12]3[CH:17]=[C:16]([OH:18])[CH:15]=[C:14]([F:19])[CH:13]=3)[C:4]=12.CCN(C(C)C)C(C)C.C(Cl)(=O)OC(Cl)C>C(Cl)Cl>[CH:24]([OH:45])=[O:23].[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:20]([C:22]3[O:23][C:24](=[O:45])[C:25]4[C:30]([C:31]=3[C:32]3[CH2:33][NH:34][CH2:35][CH2:36][CH:37]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:10]=[C:11]([C:12]3[CH:17]=[C:16]([OH:18])[CH:15]=[C:14]([F:19])[CH:13]=3)[C:4]=12

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 118131081HCID 118131081, compound

Product 1

HCID 118131274HCID 118131274, compoundYield 31.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(1-(4-Amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-benzyl-1,2,5,6-tetrahydropyridin-3-yl)-1H-isochromen-1-one hydrochloride (example 169, 0.5 g, 0.799 mmol), was dissolved in DCM (3 ml) at 0° C.; DIPEA (0.395 ml, 2.262 mmol) and 1-chloroethyl carbonochloridate (0.651 ml, 6.03 mmol) were added at 0° C. under vigorous stirring and the reaction was stirred for 5 min at 0° C. and for 2 hrs at 60° C. The reaction was allowed to cool to RT and quenched with 5 ml of MeOH; the mixture was stirred for further 2.5 hrs at 60° C. and evaporated under reduced pressure to give a crude which was purified by reverse phase flash chromatography on C-18 cartridge (H2O:CH3CN=95:5 to 50:50, with 0.1% HCOOH) to afford title compound (0.068 g, 0.125 mmol, 16%).

Workup

  1. stirringthe reaction was stirred for 5 min at 0° C. and for 2 hrs at 60° C
  2. customquenched with 5 ml of MeOH
  3. stirringthe mixture was stirred for further 2.5 hrs at 60° C.
  4. customevaporated under reduced pressure
  5. customto give a crude which
  6. customwas purified by reverse phase flash chromatography on C-18 cartridge (H2O:CH3CN=95:5 to 50:50, with 0.1% HCOOH)

Sources & evidence

ORD record
ord-973b445ae76b493a901a6dad67835f3d
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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