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

HRID 1185278ノート

反応式

HRID 1185278 の反応式
[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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-ee7191ccaa9847e9af958ce470ed3844
出典データセット
uspto-grants-2014_03
特許番号
US08669361B2

反応ノート

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