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 226390노트

반응식

HRID 226390 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d2386f0b01164b5bb7c7cb99f938ead6
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557127B2

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