Diisopropylethylamine → tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate

HRID 1185278노트

반응식

HRID 1185278 반응식
[CH2:1]1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)C[CH2:2]1.F[P-](F)(F)(F)(F)F.[Br:34][C:35]1[S:36][C:37]([NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[C:38]([C:40]([OH:42])=O)[N:39]=1.[NH2:51][C:52]1[CH:53]=[N:54][N:55]([CH3:72])[C:56]=1[N:57]1[CH2:62][CH2:61][CH:60]([CH2:63][NH:64][C:65](=[O:71])[O:66][C:67]([CH3:70])(C)C)[CH2:59][CH2:58]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:67]([O:66][C:65]([NH:64][CH2:63][CH:60]1[CH2:59][CH2:58][N:57]([C:56]2[N:55]([CH3:72])[N:54]=[CH:53][C:52]=2[NH:51][C:40]([C:38]2[N:39]=[C:35]([Br:34])[S:36][C:37]=2[NH:43][C:44](=[O:45])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:42])[CH2:62][CH2:61]1)=[O:71])[CH2:70][CH2:1][CH3:2]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 581821562-Bromo-5-((tert-butoxycarbonyl)amino)thiazole-4-carboxylic acidHCID 58464964tert-butyl (1-(4-amino-1-methyl-1H-pyrazol-5-yl)piperidin-4-yl)methylcarbamate

생성물 1

HCID 58464898tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate수율 96.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

A solution of PyBOP (2.84 g, 5.46 mmol) and 2-bromo-5-(tert-butoxycarbonylamino)thiazole-4-carboxylic acid (1.39 g, 4.29 mmol) in DCM (10 mL) was stirred at room temperature for 30 min. A solution of tert-butyl (1-(4-amino-1-methyl-1H-pyrazol-5-yl)piperidin-4-yl)methylcarbamate (1.2 g, 3.90 mmol) and DIPEA (1.1 mL, 6.24 mmol) in DCM (20 mL) was added and the mixture stirred at room temperature for 16 hr. The mixture was diluted with DCM and washed with water. The organic layer was separated, passed through a phase separation cartridge and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (0-100% EtOAc/isohexane) to yield tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate as a pink solid (2.32 g, 96%). 1H NMR (400 MHz, d6-DMSO) δ 10.62 (s, 1H), 9.64 (s, 1H), 7.23 (s, 1H), 6.86 (t, J=5.8 Hz, 1H), 3.62 (s, 3H), 3.07 (d, J=11.4 Hz, 2H), 2.95 (t, J=11.5 Hz, 2H), 2.87 (t, J=6.3 Hz, 2H), 1.67 (d, J=12.3 Hz, 2H), 1.52 (s, 9H), 1.45 (s, 1H), 1.40 (s, 9H), 1.27-1.16 (m, 2H).

후처리

  1. washwashed with water
  2. customThe organic layer was separated
  3. custompassed through a phase separation cartridge
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified via silica gel column chromatography (0-100% EtOAc/isohexane)

출처 및 근거

ORD 기록
ord-ee7191ccaa9847e9af958ce470ed3844
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669361B2

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