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Diisopropylethylamine → 1-[4-(Cyanomethyl)-1-(isopropylsulfonyl)piperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide

HRID 521243
ノート
印刷プレビュー

反応式

HRID 521243 の反応式
FC(F)(F)C([O-])=O.[C:8]([C:11]1[C:12]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:13][N:14]([C:16]2([CH2:22][C:23]#[N:24])[CH2:21][CH2:20][NH2+:19][CH2:18][CH2:17]2)[CH:15]=1)(=[O:10])[NH2:9].CCN(C(C)C)C(C)C.[CH:41]([S:44](Cl)(=[O:46])=[O:45])([CH3:43])[CH3:42]>CC#N.CN(C1C=CN=CC=1)C.CS(C)=O>[C:23]([CH2:22][C:16]1([N:14]2[CH:15]=[C:11]([C:8]([NH2:9])=[O:10])[C:12]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:13]2)[CH2:21][CH2:20][N:19]([S:44]([CH:41]([CH3:43])[CH3:42])(=[O:46])=[O:45])[CH2:18][CH2:17]1)#[N:24]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 824082-Propanesulfonyl chlorideHCID 867293834-[4-Carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidinium trifluoroacetate

生成物 1

HCID 867294191-[4-(Cyanomethyl)-1-(isopropylsulfonyl)piperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine
触媒
HCID 679Dimethyl Sulfoxide溶媒
HCID 6342Acetonitrile溶媒

実験手順

To a suspension of 4-[4-carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-1) (30 mg, 0.068 mmol) in MeCN (0.50 mL) was added DIPEA (0.030 mL, 0.17 mmol) and DMAP (12 mg, 0.10 mmol). To this mixture was added isopropylsulfonyl chloride (0.008 mL, 0.1 mmol). The resulting mixture was allowed to stir at ambient temperature for 1 hour before it was diluted with DMSO (1.0 mL) and purified directly by reverse-phase preparative HPLC (using a gradient elution of 0-100% MeCN/water, with 0.1% v/v HCOOH modifier). Desired fractions were identified, combined and concentrated in vacuo to afford the title compound, Example #37-1. 1H NMR (600 MHz, DMSO-d6): δ 9.03 (s, 1H), 8.47 (s, 1H), 7.54 (br s, 1H), 7.48 (d, J=7.8 Hz, 2H), 7.21 (t, J=7.8 Hz, 2H), 7.15 (br s, 1H), 6.80 (t, J=7.8 Hz, 1H), 3.50-3.56 (m, 2H), 3.19 (s, 2H), 2.98-3.10 (m, 2H), 2.38-2.49 (m, 3H), 2.02-2.08 (m, 2H), 1.15 (d, J=6.6 Hz, 6H). LRMS (ESI) calc'd for C20H26N6O3S [M+H]+: 431. Found: 431.

後処理

  1. custompurified directly by reverse-phase preparative HPLC (
  2. washa gradient elution of 0-100% MeCN/water
  3. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-24bbbe85f08b4f1c91f3dfdcaa3465fc
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09328099B2

反応ノート

読み込み中…

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