Diisopropylethylamine → HCID 90220274, compound

HRID 2199785Notes

Reaction equation

HRID 2199785 reaction equation
[C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:14][C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]2[S:22][C:23]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)=[C:24]([C:26]([NH2:28])=[O:27])[N:25]=2)[CH2:16]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:14][C@@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([C:21]3[S:22][C:23]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=4)=[C:24]([C:26]([NH2:28])=[O:27])[N:25]=3)[CH2:16]2)=[O:11])=[CH:7][N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218978046-tert-Butylpyridine-3-carboxylic acidHCID 90220400HCID 90220400, compound

Product 1

HCID 90220274HCID 90220274, compoundYield 66.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-tert-butylnicotinic acid (23.5 mg, 131 μmol) and 2-((R)-3-amino-piperidin-1-yl)-5-(pyridin-2-ylamino)-thiazole-4-carboxylic acid amide (38 mg, 119 μmol) in N,N-dimethylformamide (1 mL) was added diisopropylethylamine (35 μL, 200 μmol) followed by 0-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (61 mg, 161 μmol). After stirring at ambient temperature overnight under an atmosphere of argon the reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL), the mixture poured into water (5 mL) and extracted with ethyl acetate (3×3 mL). The combined organic extracts were washed with brine (2×2 mL), dried over sodium sulfate, filtered and concentrated in vacuo to a yellow solid. The crude product was purified by chromatography using a 13 g C-18 column gradient eluted from 10% acetonitrile in water up to 100% acetonitrile. The product containing fractions were combined and concentrated in vacuo and the residue lyophilized from acetonitrile/water to give (R)-2-(3-(6-tert-butylnicotinamido)piperidin-1-yl)-5-(pyridin-2-ylamino)thiazole-4-carboxamide as a pale yellow solid (37.8 mg, 66%).

Workup

  1. customwas quenched by the addition of saturated aqueous ammonium chloride (2 mL)
  2. additionthe mixture poured into water (5 mL)
  3. extractionextracted with ethyl acetate (3×3 mL)
  4. washThe combined organic extracts were washed with brine (2×2 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a yellow solid
  8. customThe crude product was purified by chromatography
  9. washeluted from 10% acetonitrile in water up to 100% acetonitrile
  10. additionThe product containing fractions
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ebc8dece443b46c687e40dc486ea4348
Source dataset
uspto-grants-2016_06
Patent number
US09359345B2

Reaction notes

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