Hydrochloric Acid → 5-bromo-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole-7-carboxamide hydrochloride

HRID 1805894노트

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HRID 1805894 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[CH:5]2.CC([N:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=C(B(O)O)C=2)C1)C.O=C1CCN(C(OC(C)(C)C)=O)CC1.S(=O)(=O)(O)N.[ClH:48]>C(O)(=O)C>[ClH:48].[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[C:19]1[CH2:24][CH2:25][NH:17][CH2:21][CH:20]=1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 5987Sulfamic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 46735171[2-(1-Methylethyl)-2,3-dihydro-1H-isoindol-5-yl]boronic acidHCID 596006575-bromo-1H-indole-7-carboxamide2회

생성물 1

HCID 671212775-bromo-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole-7-carboxamide hydrochloride

시약·촉매·용매 1

HCID 176Acetic Acid용매2회

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온도
72 °C

실험 절차

5-bromo-1H-indole-7-carboxamide (which may be prepared according to Intermediate 7, WO2005067923) (1 wt), 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (1.20 wt, 1.5 eq) and sulfamic acid (0.5 eq, 0.2031 wt) were all charged sequentially to an empty reactor. Acetic acid (5 vols) was added and the mixture was heated to 70-74° C. Held thus with stirring under nitrogen for 15-25 hrs until the level of 5-bromo-1H-indole-7-carboxamide by HPLC is <5% a/a uncorrected. A mixture of hydrochloric acid (36%, 0.52 vol, 1.5 eq) and acetic acid (0.5 vol) was prepared. This mixture was then added drop-wise to the batch over ca 30 mins, maintaining an internal temp of 65-74° C. The batch was stirred for a further 30 mins at 65-74° C. before warming to 93-97° C. Stirred within this temp range under nitrogen for 15-25 hrs, until the 2:1 dimer impurity (rrt 1.15 on 8 min reverse phase LC method) is <10% a/a uncorrected. Batch then cooled back to 15-25° C. and aged within this temp range for at least 60 mins. Product then collected by vacuum filtration and washed with IMS (2×2 vol). Dried to constant weight at 40° C. in vacuo.

후처리

  1. additionall charged sequentially to an empty reactor
  2. customwas prepared
  3. additionThis mixture was then added drop-wise to the batch over ca 30 mins
  4. temperaturemaintaining an internal temp of 65-74° C
  5. temperaturebefore warming to 93-97° C
  6. stirringStirred within this temp range under nitrogen for 15-25 hrs, until the 2:1 dimer impurity (rrt 1.15 on 8 min reverse phase LC method)
  7. temperatureBatch then cooled back to 15-25° C.
  8. waitaged within this temp range for at least 60 mins
  9. filtrationProduct then collected by vacuum filtration
  10. washwashed with IMS (2×2 vol)
  11. customDried to constant weight at 40° C. in vacuo

출처 및 근거

ORD 기록
ord-0ee4febfd3f649d9947869396f2f8c66
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354539B2

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