Diisopropylethylamine → Tert-butyl(2S)-2-[(4-{3-[1-(1,3-benzothiazol-6-yl)cyclopropyl][1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl}benzoyl)amino]-3,3-dimethylbutanoate

HRID 1099068Notes

Reaction equation

HRID 1099068 reaction equation
C(N(CC)C(C)C)(C)C.[S:10]1[C:14]2[CH:15]=[C:16]([C:19]3([C:22]4[N:26]5[N:27]=[C:28]([C:31]6[CH:39]=[CH:38][C:34]([C:35]([OH:37])=O)=[CH:33][CH:32]=6)[CH:29]=[N:30][C:25]5=[N:24][N:23]=4)[CH2:21][CH2:20]3)[CH:17]=[CH:18][C:13]=2[N:12]=[CH:11]1.Cl.[NH2:41][C@@H:42]([C:50]([CH3:53])([CH3:52])[CH3:51])[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[S:10]1[C:14]2[CH:15]=[C:16]([C:19]3([C:22]4[N:26]5[N:27]=[C:28]([C:31]6[CH:39]=[CH:38][C:34]([C:35]([NH:41][C@@H:42]([C:50]([CH3:53])([CH3:52])[CH3:51])[C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])=[O:37])=[CH:33][CH:32]=6)[CH:29]=[N:30][C:25]5=[N:24][N:23]=4)[CH2:21][CH2:20]3)[CH:17]=[CH:18][C:13]=2[N:12]=[CH:11]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 56776989tert-butyl (2S)-2-amino-3,3-dimethylbutanoate hydrochlorideHCID 668130544-{3-[1-(1,3-Benzothiazol-6-yl)cyclopropyl][1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl}benzoic acid

Product 1

HCID 66812559Tert-butyl(2S)-2-[(4-{3-[1-(1,3-benzothiazol-6-yl)cyclopropyl][1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl}benzoyl)amino]-3,3-dimethylbutanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N-Diisopropylethylamine (42 μL, 0.24 mmol) was added to a mixture of 4-{3-[1-(1,3-benzothiazol-6-yl)cyclopropyl][1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl}benzoic acid (33 mg, 0.080 mmol), tert-butyl (2S)-2-amino-3,3-dimethylbutanoate hydrochloride (23 mg, 0.10 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (42 mg, 0.096 mmol) in DMF (1 mL). The mixture was stirred at RT overnight, and quenched with saturated sodium bicarbonate (5 mL). The reaction mixture was extracted with ethyl acetate (3×5 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was flash chromatographed on a silica gel column with ethyl acetate in hexanes (40%) to afford the desired product. Analytical LCMS: (M+H)+=584.2

Workup

  1. customquenched with saturated sodium bicarbonate (5 mL)
  2. extractionThe reaction mixture was extracted with ethyl acetate (3×5 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed on a silica gel column with ethyl acetate in hexanes (40%)

Sources & evidence

ORD record
ord-6039afd0cb5e4ab99db343ca0a79805a
Source dataset
uspto-grants-2012_03
Patent number
US08143251B2

Reaction notes

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