2-Amino-3-Hydroxypyridine → (1aR,5aR)-2-(2,4-Difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid (3-Hydroxy-pyridin-2-yl)-amide

HRID 1623934ノート

反応式

HRID 1623934 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:16]2[C@@H:15]3[CH2:17][C@@H:14]3[CH2:13][C:12]=2[C:11]([C:18]([OH:20])=O)=[N:10]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[NH2:63][C:64]1[C:69]([OH:70])=[CH:68][CH:67]=[CH:66][N:65]=1>CN(C=O)C>[OH:70][C:69]1[C:64]([NH:63][C:18]([C:11]2[C:12]3[CH2:13][C@H:14]4[CH2:17][C@H:15]4[C:16]=3[N:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[N:10]=2)=[O:20])=[N:65][CH:66]=[CH:67][CH:68]=1

参加物

6

反応物 4

HCID 281142-Amino-3-HydroxypyridineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 68182595HCID 68182595、化合物

生成物 1

HCID 86669677(1aR,5aR)-2-(2,4-Difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid (3-Hydroxy-pyridin-2-yl)-amide収率 30%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Intermediate 1 (see Example 1.1, 50 mg, 0.181 mmol) was dissolved in DMF (1 mL). PyBOP (104 mg, 0.199 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.098 mL, 0.561 mmol) were added. The reaction mixture was stirred at room temperature for about 3 min. 2-aminopyridin-3-ol (19.93 mg, 0.181 mmol) was then added to the mixture to give an amber solution which was stirred overnight at room temperature. The mixture was purified by HPLC to provide the title compound (20 mg). LCMS m/z=369.2 [M+H]+; 1H NMR: (400 MHz, CD3CN) δ ppm 0.53 (td, J=4.8 and 3.5 Hz, 1H), 1.23 (td, J=7.9 and 4.8 Hz, 1H), 2.21-2.27 (m, 1H), 2.33-2.40 (m, 1H), 2.93 (d, J=16.5 Hz, 1H), 3.05 (dd, J=16.6 and 6.3 Hz, 1H), 7.16-7.23 (m, 1H), 7.23-7.32 (m, 2H), 7.73-7.83 (m, 3H), 9.80 (s, 1H).

後処理

  1. customto give an amber solution which
  2. stirringwas stirred overnight at room temperature
  3. customThe mixture was purified by HPLC

出典と根拠

ORDレコード
ord-ca32b2ee8e6c44868834c29a165ca7fc
出典データセット
uspto-grants-2014_07
特許番号
US08778950B2

反応ノート

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