Ammonia → (S)-tert-Butyl 2-((1R,2R)-2-(4-bromophenyl)-1-carbamoyl-cyclopropylcarbamoyl)piperidine-1-carboxylate

HRID 600313노트

반응식

HRID 600313 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:10][C@:9]2([NH:14][C:15]([C@@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][N:18]2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:16])[C:11]([OH:13])=O)=[CH:4][CH:3]=1.C([N:32]1CCOCC1)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.N>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:10][C@:9]2([NH:14][C:15]([C@@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][N:18]2[C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])=[O:16])[C:11](=[O:13])[NH2:32])=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 222Ammonia2회HCID 7525EthylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2회HCID 57999663(1R,2R)-2-(4-Bromophenyl)-1-((S)-1-(tert-butoxycarbonyl)piperidine-2-carboxamido)cyclopropanecarboxylic Acid

생성물 1

HCID 57999645(S)-tert-Butyl 2-((1R,2R)-2-(4-bromophenyl)-1-carbamoyl-cyclopropylcarbamoyl)piperidine-1-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(1R,2R)-2-(4-Bromophenyl)-1-((S)-1-(tert-butoxycarbonyl)piperidine-2-carboxamido)cyclopropanecarboxylic acid (3 g) was dissolved in DMF (17 mL) and to the solution was added N-ethylmorpholine (1.219 mL) followed by TBTU (3.09 g). The reaction mixture was stirred at RT for 20 min then it was cooled to 0° C. Aqueous ammonia (1.461 mL) was added and the mixture was allowed to reach RT over 1 h. The reaction appeared to have proceeded ˜70%, so it was left to stir for a further 2 h. LCMS showed little change so further TBTU (400 mg) and ammonia (0.3 mL) were added, and the mixture stirred for a further 2 h. The reaction mixture was partitioned between ethyl acetate and diluted brine, and reextracted into ethyl acetate twice more. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound (2.75 g) as a pale gum.

후처리

  1. temperatureit was cooled to 0° C
  2. waitto reach RT over 1 h
  3. waitso it was left
  4. stirringto stir for a further 2 h
  5. additionwere added
  6. stirringthe mixture stirred for a further 2 h
  7. customThe reaction mixture was partitioned between ethyl acetate and diluted brine
  8. dry with materialThe combined organic phases were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-d9cc49c1049a4d689ca04d0fae8d1423
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902181B2

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