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 2376076ノート

反応式

HRID 2376076 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-37663df32f67442ca3bc2a0e86e6ff00
出典データセット
uspto-grants-2008_12
特許番号
US07465731B2

反応ノート

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