Diisopropylethylamine → N-{(1R,3S,4S)-2-[2-Amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[2.2.1]hept-3-ylmethyl}-2,2,2-trifluoro-acetamide
Reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[C:27]([C:29]([OH:31])=O)[N:28]=1.[C@H:39]12[CH2:45][C@H:42]([CH2:43][CH2:44]1)[C@@H:41]([CH2:46][NH:47][C:48](=[O:53])[C:49]([F:52])([F:51])[F:50])[NH:40]2.CCN(C(C)C)C(C)C>CN(C=O)C.CC(OC)(C)C>[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[C:27]([C:29]([N:40]2[C@H:41]([CH2:46][NH:47][C:48](=[O:53])[C:49]([F:51])([F:52])[F:50])[C@@H:42]3[CH2:45][C@H:39]2[CH2:44][CH2:43]3)=[O:31])[N:28]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
TBTU (1.70 mmol, 1.10 eq) is added to a solution of 2-amino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid (1.62 mmol, 1.05 eq), N-[(1R,3S,4S)-1-(2-Aza-bicyclo[2.2.1]hept-3-yl)methyl]-2,2,2-trifluoro-acetamide (1.55 mmol, 1.0 eq) and DIPEA (5.41 mmol, 3.5 eq) in DMF (10 mL). After 90 min the mixture is diluted with TBME (50 mL) and washed three times with an aq. NaOH solution (0.5 M, 50 mL each). The combined aq. layers are extracted twice with TBME (30 mL each). The organic layers are combined, washed with water (3×30 mL) and brine (30 mL), dried over MgSO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS (basic): tR=0.82 min; [M+H]+=442.9.
Workup
- washwashed three times with an aq. NaOH solution (0.5 M, 50 mL each)
- extractionThe combined aq. layers are extracted twice with TBME (30 mL each)
- washwashed with water (3×30 mL) and brine (30 mL)
- dry with materialdried over MgSO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-ea3351da984e48ac9d25900e0e2c29b5
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08236801B2
Reaction notes
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