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Dimethylformamide → (R)-N2-[N-[(1,1-Dimethylethoxy)carbonyl]-4-nitro-L-phenylalanyl]-N-(1-methyl-2-phenylethyl)-L-allothreoninamide

HRID 864098
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HRID 864098 반응식
[C:1]([NH:8][C@H:9](C(O)=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH2:23].ON1[C:29]2C=CC=C[C:28]=2N=N1.Cl.CN(C)[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]N=C=N.[C:46](O)([C:48](F)(F)F)=[O:47].C[N:54]1[CH2:59]CO[CH2:56][CH2:55]1.[Cl-].[Na+].O.O.C[N:65]([CH3:68])[CH:66]=[O:67]>>[CH3:7][C:4]([CH3:5])([O:3][C:1]([NH:8][C@H:9]([C:66]([NH:65][C@@H:68]([C:59]([NH:54][CH:55]([CH3:56])[CH2:37][C:38]1[CH:29]=[CH:28][CH:41]=[CH:40][CH:39]=1)=[O:23])[C@H:46]([CH3:48])[OH:47])=[O:67])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][CH:16]=1)=[O:2])[CH3:6]
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참가 물질

8

반응물 7

HCID 6228Dimethylformamide2회HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 27960291-Hydroxybenzotriazole hydrateHCID 7021882N-(tert-Butoxycarbonyl)-4-nitro-L-phenylalanineHCID 23713072Sodium chloride dihydrate
HCID 57482816
1-(3-Dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride

생성물 1

HCID 131719590(R)-N2-[N-[(1,1-Dimethylethoxy)carbonyl]-4-nitro-L-phenylalanyl]-N-(1-methyl-2-phenylethyl)-L-allothreoninamide수율 98%

실험 절차

To a solution of Part A compound (0.418 g, 1.29 mmol, 1.00 eq.) in dichloromethane (2.2 mL) under argon at 0° C. was added trifluoroacetic acid (1.5 mL, 19.5 mmol, 15.1 eq.). After 4.0 hr, trifluoroacetic acid (5 mL, 64.8 mmol, 5.44 eq.) was added. After 5 hr, the reaction mixture was concentrated in vacuo to give the crude TFA salt of Part A compound. To a solution of Boc-4-nitro-L-phenylalanine (0.441 g, 1.42 mmol, 1.10 eq.) and 1-hydroxybenzo-triazole hydrate (0.193 g, 1.43 mmol, 1.10 eq.) in dimethylformamide (5.0 mL) at 0° C. was added 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride (0.273 g, 1.43 mmol, 1.10 eq.). After 0.5 hr, a solution of crude TFA salt of Part A compound (1.29 mmol, 1.00 eq.) in dimethylformamide (3.0 mL) was added, which was then followed by 4-methylmorpholine (0.5 mL, 4.55 mmol, 3.52 eq.). After 21 hr, the reaction mixture was poured into a brine/water solution (1:1) and extracted with ethyl acetate twice. The organic layers were combined and washed with aqueous 0.25M potassium hydrogen sulfate, water, aqueous saturated sodium bicarbonate and water, successively. The organic layer was concentrated in vacuo to give title compound (0.651 g, 98.0%):

후처리

  1. waitAfter 21 hr
  2. extractionextracted with ethyl acetate twice
  3. washwashed with aqueous 0.25M potassium hydrogen sulfate, water, aqueous saturated sodium bicarbonate and water
  4. concentrationThe organic layer was concentrated in vacuo

출처 및 근거

ORD 기록
ord-6517ef4b1f8d4574806198650a083288
출처 데이터셋
uspto-grants-1996_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05561146

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