Diisopropylethylamine → (S)-tert-butyl 16-(3-(4-chloro-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-4,7,10,13-tetraoxahexadecan-1-oate

HRID 1408230Notes

Reaction equation

HRID 1408230 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][N:27]=1)[C:12]([NH:14][C@@H:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][CH2:16]1)=[O:13].[CH3:28][C:29]([CH3:58])([O:31][C:32](=[O:57])[CH2:33][CH2:34][O:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][CH2:47][C:48]1[CH:49]=[C:50]([CH:54]=[CH:55][CH:56]=1)[C:51](O)=[O:52])[CH3:30].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(C1C=CN=CC=1)C.CN(C=O)C>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:51]([C:50]2[CH:49]=[C:48]([CH2:47][CH2:46][CH2:45][O:44][CH2:43][CH2:42][O:41][CH2:40][CH2:39][O:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][C:32]([O:31][C:29]([CH3:58])([CH3:30])[CH3:28])=[O:57])[CH:56]=[CH:55][CH:54]=2)=[O:52])=[C:3]([C:9]2[CH:10]=[C:11]([C:12](=[O:13])[NH:14][C@@H:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18][CH2:17][CH2:16]3)[CH:25]=[CH:26][N:27]=2)[CH:4]=1

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 665868913-(3-(2-(2-(2-(3-Tert-butoxy-3-oxopropoxy)ethoxy)ethoxy)ethoxy)propyl)benzoic acidHCID 66587450(S)-2-(2-amino-5-chlorophenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)isonicotinamide

Product 1

HCID 66587466(S)-tert-butyl 16-(3-(4-chloro-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-4,7,10,13-tetraoxahexadecan-1-oateYield 66.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (S)-2-(2-amino-5-chlorophenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)isonicotinamide 237b (1.02 g, 2.7 mmol), 3-(2,2-dimethyl-4-oxo-3,7,10,13,16-pentaoxanonadecan-19-yl)benzoic acid 251c (1.19 g, 2.7 mmol), DIPEA (1.04 g, 8.1 mmol) and DMAP (190 mg, 1.55 mmol) in DMF (20 ml) was added HATU (1.13 g, 2.97 mmol). The reaction mixture was heated at 65° C. for 24 hours, then cooled and concentrated. The residue was combined with another run (0.28 mmol scale), dissolved in DCM (150 mL), washed with water (4×50 mL), dried (Na2SO4) and concentrated to dryness. Purification by flash chromatography on silica gel (10% to 30% EtOAc in DCM) gave the title compound (1.44 g).

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. dissolutiondissolved in DCM (150 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 (10% to 30% EtOAc in DCM)

Sources & evidence

ORD record
ord-4d738d82d4d54d3791affd265ddef2eb
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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