1,2-Dichloroethane → (S)-4-(tert-butyl)-N-(3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)-1-(methyl sulfonamido)-1-oxopropan-2-yl)benzamide

HRID 1775850Notes

Reaction equation

HRID 1775850 reaction equation
[C:1]([C:5]1[CH:44]=[CH:43][C:8]([C:9]([NH:11][C@@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[N:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[CH:31][CH:30]=4)=[CH:25][N:24]=3)=[CH:19][CH:18]=2)[C:13](O)=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:45][S:46]([NH2:49])(=[O:48])=[O:47].C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C.CC(=O)OCC>[C:1]([C:5]1[CH:44]=[CH:43][C:8]([C:9]([NH:11][C@@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[N:28]=[CH:27][C:26]([C:29]4[CH:30]=[CH:31][C:32]([O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[CH:33][CH:34]=4)=[CH:25][N:24]=3)=[CH:19][CH:18]=2)[C:13]([NH:49][S:46]([CH3:45])(=[O:48])=[O:47])=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 72879MethanesulfonamideHCID 86582069(S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoic acid

Product 1

HCID 86582532(S)-4-(tert-butyl)-N-(3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)-1-(methyl sulfonamido)-1-oxopropan-2-yl)benzamideYield 40%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoic acid Compound 85 (78.0 mg, 0.13 mmol), methanesulfonamide (20.0 mg, 0.21 mmol), and DMAP (16.1 mg, 0.13 mmol) in DMF (1.5 mL) was added EDC (40.3 mg, 0.21 mmol) and the solution stirred overnight at room temperature. The reaction mixture was diluted in EA (50 mL), washed with aqueous saturated sodium bicarbonate (2×20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure. The crude product was purified by chromatography (hexane/EA) to afford 36 mg (40%) of (S)-4-(tert-butyl)-N-(3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)-1-(methylsulfonamido)-1-oxopropan-2-yl)benzamide, Compound 299 as a colorless solid. LCMS-ESI (m/z) calculated for C38H46N4O5S: 670.3. found 671.3 [M+H]+, tR=11.01 min (Method 10).

Workup

  1. washwashed with aqueous saturated sodium bicarbonate (2×20 mL) and brine (20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure
  5. customThe crude product was purified by chromatography (hexane/EA)

Sources & evidence

ORD record
ord-6487db5b035f4053bf71cf6206d673ec
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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