Diisopropylethylamine → tert-Butyl[(1R,2R)-2-({[5-ethenyl-4-(imidazo[1,2-b]pyridazin-3-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate

HRID 2046409Notes

Reaction equation

HRID 2046409 reaction equation
[CH:1]([C:3]1[S:7][C:6]([C:8]([OH:10])=O)=[CH:5][C:4]=1[C:11]1[N:15]2[N:16]=[CH:17][CH:18]=[CH:19][C:14]2=[N:13][CH:12]=1)=[CH2:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:47][C@H:48]1[C:53]([F:55])([F:54])[CH2:52][CH2:51][CH2:50][C@H:49]1[NH:56][C:57](=[O:63])[O:58][C:59]([CH3:62])([CH3:61])[CH3:60].C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[C:59]([O:58][C:57](=[O:63])[NH:56][C@@H:49]1[CH2:50][CH2:51][CH2:52][C:53]([F:55])([F:54])[C@@H:48]1[NH:47][C:8]([C:6]1[S:7][C:3]([CH:1]=[CH2:2])=[C:4]([C:11]2[N:15]3[N:16]=[CH:17][CH:18]=[CH:19][C:14]3=[N:13][CH:12]=2)[CH:5]=1)=[O:10])([CH3:62])([CH3:60])[CH3:61]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 580464365-Ethenyl-4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxylic acidHCID 59603811tert-Butyl ((1R,2R)-2-amino-3,3-difluorocyclohexyl)carbamate

Product 1

HCID 91321603tert-Butyl[(1R,2R)-2-({[5-ethenyl-4-(imidazo[1,2-b]pyridazin-3-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-ethenyl-4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxylic acid (105 mg, 0.387 mmol) and BOP (257 mg, 0.581 mmol) in DMF (5.2 mL) was added tert-butyl [(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (145 mg, 0.581 mmol) followed by diisopropylethyl amine (0.169 mL, 0.968 mmol). The mixture was allowed to stir at room temperature for 18 h. After the reaction was complete, water was added and the aqueous layer extracted with ethyl acetate (×3). The organic layers were combined, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography giving the title compound as an orange solid. LRMS (APCI) calc'd for (C24H27F2N5O3S) [M+H]+, 504.2. found 504.1.

Workup

  1. extractionthe aqueous layer extracted with ethyl acetate (×3)
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-3c9296fe76434eeea22115153b0ec721
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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