Lithium → (2R)-N-((1S,2R)-3-(((4S)-6-bromo-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-4-((4-propyl-1H-1,2,3-triazol-1-yl)acetyl)-2-morpholinecarboxamide

HRID 253148

Reaction equation

HRID 253148 reaction equation
[CH2:1]([C:4]1[N:5]=[N:6][N:7]([CH2:9][C:10]([N:12]2[CH2:17][CH2:16][O:15][CH:14]([C:18]([OH:20])=O)[CH2:13]2)=[O:11])[CH:8]=1)[CH2:2][CH3:3].[Li].[NH2:22][C@@H:23]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@H:24]([OH:40])[CH2:25][NH:26][C@@H:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([Br:37])[CH:35]=2)[O:30][C:29]([CH3:39])([CH3:38])[CH2:28]1.[CH3:48]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:37][C:34]1[CH:35]=[C:36]2[C:31](=[CH:32][CH:33]=1)[O:30][C:29]1([CH2:39][CH2:48][CH2:38]1)[CH2:28][C@@H:27]2[NH:26][CH2:25][C@@H:24]([OH:40])[C@@H:23]([NH:22][C:18]([C@@H:14]1[O:15][CH2:16][CH2:17][N:12]([C:10](=[O:11])[CH2:9][N:7]2[CH:8]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]=[N:6]2)[CH2:13]1)=[O:20])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 3028194LithiumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66844876(2R,3S)-3-amino-1-((S)-6-bromo-2,2-dimethylchroman-4-ylamino)-4-phenylbutan-2-olHCID 668453864-(2-(4-propyl-1H-1,2,3-triazol-1-yl)acetyl)morpholine-2-carboxylic acid

Product 1

HCID 66844854(2R)-N-((1S,2R)-3-(((4S)-6-bromo-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-4-((4-propyl-1H-1,2,3-triazol-1-yl)acetyl)-2-morpholinecarboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 15-mL RBF, the 4-(2-(4-propyl-1H-1,2,3-triazol-1-yl)acetyl)morpholine-2-carboxylic acid (0.034 g, 0.11 mmol) as the crude lithium salt and (2R,3S)-3-amino-1-((S)-6-bromo-2,2-dimethylchroman-4-ylamino)-4-phenylbutan-2-ol (0.046 g, 0.11 mmol) were taken up in DMF (1.5 mL). When the solids had dissolved, HATU (0.041 g, 0.11 mmol) was added. After 14 h, the reaction was concentrated, and the residue was taken up in EtOAc (60 mL) and the organic layer was extracted with water (5 mL), dried over sodium sulfate and concentrated. The residue was purified through silica gel (15 mL) which had been deactivated with TEA (2.0 mL) eluting with 4% MeOH-EtOAc, to afford the title compound as a 1:1 mixture of diastereomers. MS m/z 695/697 (M+1).

Workup

  1. dissolutionWhen the solids had dissolved
  2. concentrationthe reaction was concentrated
  3. extractionthe organic layer was extracted with water (5 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified through silica gel (15 mL) which
  7. washeluting with 4% MeOH-EtOAc

Sources & evidence

ORD record
ord-3d10066892cb490d890fafe962ab9915
Source dataset
uspto-grants-2011_01
Patent number
US07872009B2

Linked notes

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