N-Methyl-4-anisidine → HCID 90289952, compound

HRID 1471632Notes

Reaction equation

HRID 1471632 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[CH3:54][O:55][C:56]1[CH:63]=[CH:62][C:59]([NH:60][CH3:61])=[CH:58][CH:57]=1>CN(C=O)C.CCOC(C)=O>[Br:20][C:16]1[CH:15]=[C:14]([CH2:13][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10]([N:60]([C:59]2[CH:62]=[CH:63][C:56]([O:55][CH3:54])=[CH:57][CH:58]=2)[CH3:61])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 22250N-Methyl-4-anisidineHCID 81531DiisopropylethylamineHCID 2734476Boc-L-3-BromophenylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 90289952HCID 90289952, compoundYield 86.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-(tert-Butoxycarbonylamino)-3-(3-bromophenyl)propanoic acid (660 mg, 1.92 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 803 mg, 2.1 mmol) and DIPEA (0.43 ml, 2.5 mmol) were dissolved in DMF (10 ml) and treated with 4-methoxy-N-methylaniline (316 g, 2.3 mmol). The mixture was stirred vigorously overnight. The mixture was diluted with EtOAc (100 ml) and washed with brine (2×50 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The oily crude product was introduced to a silica gel loading column and purified by column chromatography (15-38% EtOAc/hexanes) to provide the desired product (770 mg, 1.66 mmol), 86.5%. MS (m/z) 463 [M+H]+.

Workup

  1. washwashed with brine (2×50 ml)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionThe oily crude product was introduced to a silica gel loading column
  6. custompurified by column chromatography (15-38% EtOAc/hexanes)

Sources & evidence

ORD record
ord-31c8db288ec74652bea63cc880bfcfa7
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

Loading…