Diisopropylethylamine → HCID 178481750、化合物

HRID 246785ノート

反応式

HRID 246785 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Cl.[NH2:33][CH:34]1[CH2:37][CH:36]([OH:38])[CH2:35]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O.CN(C=O)C>[OH:38][C@@H:36]1[CH2:37][C@H:34]([NH:33][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:30])[CH3:31])[CH:19]=2)=[O:22])[CH2:35]1.[OH:38][C@H:36]1[CH2:37][C@H:34]([NH:33][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:30])[CH3:31])[CH:19]=2)=[O:22])[CH2:35]1

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 533084663-Aminocyclobutanol hydrochlorideHCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 2

HCID 178481750HCID 178481750、化合物収率 48%HCID 178481751HCID 178481751、化合物収率 35%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A flask was charged with 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (250 mg, 0.57 mmol), 3-aminocyclobutanol hydrochloride (98 mg, 0.79 mmol) and DMF (2.8 mL). N,N-diisopropylethylamine (266 mg, 0.36 mL, 2.06 mmol) was added followed by HATU (237 mg, 0.62 mmol). The yellow solution was stirred at room temperature overnight (a precipitate was formed). The reaction mixture was diluted with water and petroleum ether. The suspension was filtered. The solid was washed with water and a little petroleum ether. The resulting off-white powder was dried under high vacuum. The mixture of cis- and trans-product (265 mg off-white powder) was submitted for further separation by SFC chromatography (KROMASIL OD 3×25 cm, 25% MeOH/CO2+0.1% Triethylamine) to afford 139 mg (48%) 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclobutyl)-amide as an off-white solid and 102 mg (35%) 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-hydroxy-cyclobutyl)-amide as an off-white solid.

後処理

  1. customwas formed)
  2. filtrationThe suspension was filtered
  3. washThe solid was washed with water
  4. customThe resulting off-white powder was dried under high vacuum
  5. additionThe mixture of cis- and trans-product (265 mg off-white powder)
  6. customwas submitted for further separation by SFC chromatography (KROMASIL OD 3×25 cm, 25% MeOH/CO2+0.1% Triethylamine)

出典と根拠

ORDレコード
ord-8aa638b4ca7744a6930d6705c230e414
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…