1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide

HRID 226390Notes

Reaction equation

HRID 226390 reaction equation
CCN=C=NCCCN(C)C.[Cl:12][C:13]1[CH:14]=[C:15](/[CH:33]=[C:34](\[F:38])/[C:35](O)=[O:36])[CH:16]=[N:17][C:18]=1[NH:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:21]1.[O:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]1[O:45][NH2:46].C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[Cl:12][C:13]1[CH:14]=[C:15](/[CH:33]=[C:34](\[F:38])/[C:35]([NH:46][O:45][CH:40]2[CH2:41][CH2:42][CH2:43][CH2:44][O:39]2)=[O:36])[CH:16]=[N:17][C:18]=1[NH:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)[CH2:21]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68961945(2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoroacrylic acid

Product 1

HCID 86603698(2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamideYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

EDCI (0.32 g) was added to the solution of (2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoroacrylic acid (0.68 g), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.24 g), and HOBT (0.28 g) in DMF (13.6 ml) and the mixture was stirred at ambient temperature for 20 hr. The reaction mixture was poured into a mixture of AcOEt and aq NaHCO3. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was crystallization with solution of iPE and hexane to give (2Z)-3-(5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}-3-pyridinyl)-2-fluoro-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (0.57 g).

Workup

  1. washThe separated organic layer was washed with water
  2. dry with materialdried over magnesium sulfate
  3. customevaporated in vacuo
  4. customcrystallization with solution of iPE and hexane

Sources & evidence

ORD record
ord-d2386f0b01164b5bb7c7cb99f938ead6
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

Loading…