N,N-Dimethylglycine → Tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(2-(dimethylamino)acetamido)pyridin-4-yloxy)methyl)piperidine-1-carboxylate

HRID 556813ノート

反応式

HRID 556813 の反応式
CN(C)CCCN=C=NCC.[NH2:12][C:13]1[C:14]([O:28][CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]2)=[CH:15][C:16]([NH:19][C:20]2[CH:25]=[N:24][C:23]([C:26]#[N:27])=[CH:22][N:21]=2)=[N:17][CH:18]=1.[CH3:43][N:44]([CH3:49])[CH2:45][C:46](O)=[O:47].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[C:26]([C:23]1[N:24]=[CH:25][C:20]([NH:19][C:16]2[CH:15]=[C:14]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)[C:13]([NH:12][C:46](=[O:47])[CH2:45][N:44]([CH3:49])[CH3:43])=[CH:18][N:17]=2)=[N:21][CH:22]=1)#[N:27]

参加物

7

反応物 5

HCID 673N,N-DimethylglycineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 59613369tert-Butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-yloxy)methyl)piperidine-1-carboxylate

生成物 1

HCID 59613336Tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(2-(dimethylamino)acetamido)pyridin-4-yloxy)methyl)piperidine-1-carboxylate収率 14.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide (95 mg, 0.49 mmol) was added to a solution of tert-butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-yloxy)methyl)piperidine-1-carboxylate (140 mg, 0.33 mmol), N,N-dimethylglycine (51 mg, 0.49 mmol), 1-hydroxybenzotriazole hydrate (76 mg, 0.49 mmol) and N-ethyldiisopropylamine (86 μL, 0.49 mmol) in DMF (4 mL). The mixture was stirred overnight at room temperature then partitioned between ethyl acetate and water. The organic phase was washed sequentially with water, dilute sodium bicarbonate solution and brine, then dried (Na2SO4) and concentrated. Preparative HPLC gave tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(2-(dimethylamino)acetamido)pyridin-4-yloxy)methyl)piperidine-1-carboxylate (24 mg, 14%) as an off-white powder.

後処理

  1. customthen partitioned between ethyl acetate and water
  2. washThe organic phase was washed sequentially with water, dilute sodium bicarbonate solution and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-c31a2a93c36544bd9c07a22ca08eaa25
出典データセット
uspto-grants-2011_11
特許番号
US08058045B2

反応ノート

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