Diisopropylethylamine → Tert-butyl 16-(3-(4-(diethylamino)-2-(4-(3-(trifluoromethyl)benzyl carbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-4,7,10,13-tetraoxahexadecan-1-oate

HRID 1408228Notes

Reaction equation

HRID 1408228 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])=[CH:4][C:3]=1[C:13]1[CH:14]=[C:15]([CH:30]=[CH:31][N:32]=1)[C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=1)=[O:17].[CH3:33][C:34]([CH3:63])([O:36][C:37](=[O:62])[CH2:38][CH2:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][CH2:50][CH2:51][CH2:52][C:53]1[CH:54]=[C:55]([CH:59]=[CH:60][CH:61]=1)[C:56](O)=[O:57])[CH3:35].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.NC1C=CC(N(CC)CC)=CC=1C1C=C(C=CN=1)C(NCC1C=CC=C(C(F)(F)F)C=1)=O>[CH2:9]([N:8]([CH2:11][CH3:12])[C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:56]([C:55]2[CH:54]=[C:53]([CH2:52][CH2:51][CH2:50][O:49][CH2:48][CH2:47][O:46][CH2:45][CH2:44][O:43][CH2:42][CH2:41][O:40][CH2:39][CH2:38][C:37]([O:36][C:34]([CH3:63])([CH3:35])[CH3:33])=[O:62])[CH:61]=[CH:60][CH:59]=2)=[O:57])=[C:3]([C:13]2[CH:14]=[C:15]([C:16](=[O:17])[NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:27])([F:28])[F:29])[CH:21]=3)[CH:30]=[CH:31][N:32]=2)[CH:4]=1)[CH3:10]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66586798HCID 66586798, compoundHCID 665868913-(3-(2-(2-(2-(3-Tert-butoxy-3-oxopropoxy)ethoxy)ethoxy)ethoxy)propyl)benzoic acid

Product 1

HCID 67512796Tert-butyl 16-(3-(4-(diethylamino)-2-(4-(3-(trifluoromethyl)benzyl carbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-4,7,10,13-tetraoxahexadecan-1-oateYield 77.3%

Reagents, catalysts & solvents 2

HCID 66586798HCID 66586798, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2-amino-5-(diethylamino)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide (1.77 g, 4.0 mmol), 3-(2,2-dimethyl-4-oxo-3,7,10,13,16-pentaoxanonadecan-19-yl)benzoic acid (1.70 g, 3.86 mmol) and DIPEA (1.47 g, 11.4 mmol) in DMF (20 ml) was added HATU (1.56 g, 4.10 mmol). The reaction mixture was stirred for 30 minutes, at which time additional 2-(2-amino-5-(diethylamino)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide (0.06 g, 0.14 mmol) was added. After stirring an additional 25 minutes, the reaction mixture was concentrated under vacuum. The residue was dissolved in DCM (200 mL), washed with water (4×50 mL), dried (Na2SO4) and concentrated to dryness. Purification by flash chromatography on silica gel (50% to 100% EtOAc in hexanes) gave the title compound (2.58 g) as an oil.

Workup

  1. additionwas added
  2. concentrationthe reaction mixture was concentrated under vacuum
  3. dissolutionThe residue was dissolved in DCM (200 mL)
  4. washwashed with water (4×50 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to dryness
  7. customPurification by flash chromatography on silica gel (50% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5b58917933c147aaa628d7bca76bc9b0
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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