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

HRID 556813노트

반응식

HRID 556813 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c31a2a93c36544bd9c07a22ca08eaa25
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08058045B2

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