Diisopropylethylamine → HCID 44467684, compound

HRID 2046968Notes

Reaction equation

HRID 2046968 reaction equation
[Cl:1][C:2]1[C:3]([NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[S:36]([CH:39]([CH3:41])[CH3:40])(=[O:38])=[O:37])=[N:4][C:5]([NH:8][C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][N:14]([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[C:15]3=[O:18])=[CH:11][C:10]=2[O:25][CH:26]([CH3:28])[CH3:27])=[N:6][CH:7]=1.C(OC([N:49]1[CH2:52][CH:51]([C:53](O)=[O:54])[CH2:50]1)=O)(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH:49]1[CH2:52][CH:51]([C:53]([N:22]2[CH2:21][CH2:20][CH:19]([N:14]3[CH2:13][C:12]4[C:16](=[CH:17][C:9]([NH:8][C:5]5[N:4]=[C:3]([NH:29][C:30]6[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=6[S:36]([CH:39]([CH3:41])[CH3:40])(=[O:38])=[O:37])[C:2]([Cl:1])=[CH:7][N:6]=5)=[C:10]([O:25][CH:26]([CH3:28])[CH3:27])[CH:11]=4)[C:15]3=[O:18])[CH2:24][CH2:23]2)=[O:54])[CH2:50]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248164386-(5-Chloro-4-(2-(isopropylsulfonyl)phenylamino)-pyrimidin-2-ylamino)-5-isopropoxy-2-(piperidin-4-yl)isoindolin-1-one

Product 1

HCID 44467684HCID 44467684, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)-pyrimidin-2-ylamino)-5-isopropoxy-2-(piperidin-4-yl)isoindolin-1-one C (41 mg, 0.07 mmol) in DMF (1.0 mL) was added 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (14 mg, 0.07 mmol), HATU (39 mg, 0.104 mmol), and DIEA (0.138 mmol, 24 μL) sequentially. The reaction mixture was stirred for 1 h, then partitioned between EtOAc and water. The organic extracts were dried (Na2SO4), and concentrated in vacuo. The crude product was stirred in a solution of DCM (1 mL) and TFA (1 mL) at room temperature for 1 h. The resulting solution was concentrated and then purified by preparative RP-HPLC to afford 2-(1-(azetidine-3-carbonyl)piperidin-4-yl)-6-(5-chloro-4-(2-(isopropylsulfonyl)phenyl-amino)pyrimidin-2-ylamino)-5-isopropoxyisoindolin-1-one.

Workup

  1. custompartitioned between EtOAc and water
  2. dry with materialThe organic extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. stirringThe crude product was stirred in a solution of DCM (1 mL) and TFA (1 mL) at room temperature for 1 h
  5. concentrationThe resulting solution was concentrated
  6. custompurified by preparative RP-HPLC

Sources & evidence

ORD record
ord-94f180b1c6e4468c9471ca84f3fe6a99
Source dataset
uspto-grants-2013_11
Patent number
US08592432B2

Reaction notes

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