4-Methylmorpholine → HCID 178427474、化合物

HRID 2281578ノート

反応式

HRID 2281578 の反応式
[S:1]([NH:11][C@H:12]([C:20](O)=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].CN1CCOCC1.Cl.Cl.[NH:32]1[C:36]2([CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH2:35][NH:34]/[C:33]/1=[N:42]\[C:43]([C:45]1[C:50]([NH2:51])=[N:49][C:48]([NH2:52])=[C:47]([Cl:53])[N:46]=1)=[O:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[C:14]1([CH2:13][C@H:12]([NH:11][S:1]([C:4]2[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=2)(=[O:2])=[O:3])[C:20]([N:39]2[CH2:40][CH2:41][C:36]3([NH:32]/[C:33](=[N:42]/[C:43]([C:45]4[C:50]([NH2:51])=[N:49][C:48]([NH2:52])=[C:47]([Cl:53])[N:46]=4)=[O:44])/[NH:34][CH2:35]3)[CH2:37][CH2:38]2)=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 99327N-((4-Methylphenyl)sulfonyl)-L-phenylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178478673HCID 178478673、化合物

生成物 1

HCID 178427474HCID 178427474、化合物

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of Tosyl-L-phenylalanine (1.0 g, 3.13 mmol) in DMF (25 ml) is added N-methyl morpholine (1.033 ml, 9.39 mmol) and 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide dihydrochloride (Ex. 38) (1.37 g, 3.44 mmol), followed by HATU (1.31 g, 3.44 mmol) and the resulting solution is stirred at room temperature for 20 minutes. The crude product is diluted with water (300 ml) and the resultant solid is isolated. Purification by reverse phase chromatography (Isolute™ C18, 0-100% MeCN in water−0.1% TFA) followed by catch and release resin (SCX-2) eluted with MeOH and 7M NH3 in MeOH yields a yellow solid which is triturated with MeOH and diethyl ether to give the title compound as a free base. The free base is stirred in 5M HCl at 100° C. for 30 minutes forming a gum. MeOH (5 ml) is added to the gum and then all solvent is removed in vacuo. The residue is triturated with MeOH and diethyl ether to give the title compound; [M+H]+ 626.4; 1H NMR (DMSO-d6): 1.12-1.71 (4H, m), 2.36-2.38 (3H, s), 2.59-2.83 (2H, m), 2.93-3.52 (4H, m), 3.41-3.60 (2H, m), 4.42 (1H, m), 7.12 (2H, d, J=6.9 Hz), 7.17-7.28 (3H, m), 7.35 (2H, d, J=7.7 Hz), 7.54-7.37 (2H, br), 7.57 (2H, d, J=7.7 Hz), 8.12 (1H, d, J=9.0 Hz), 7.70-8.26 (2H, br), 9.22 (1H, s), 9.95 (1H, s), 10.99 (1H, s).

後処理

  1. customthe resultant solid is isolated
  2. customPurification by reverse phase chromatography (Isolute™ C18, 0-100% MeCN in water−0.1% TFA)
  3. washeluted with MeOH and 7M NH3 in MeOH
  4. customyields a yellow solid which
  5. customis triturated with MeOH and diethyl ether

出典と根拠

ORDレコード
ord-df9a0af0cc224b7b8e371314ca0ac8af
出典データセット
uspto-grants-2015_09
特許番号
US09139586B2

反応ノート

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