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Diisopropylethylamine → tert-Butyl 2-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)morpholine-4-carboxylate

HRID 1485223
ノート
印刷プレビュー

反応式

HRID 1485223 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:26]=[C:25]([CH2:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[CH2:35][C:36](O)=[O:37])[C:24]([C:39]([F:42])([F:41])[F:40])=[CH:23][N:22]=3)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[NH4+].[NH4+].C[N:50](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.[Cl-].[Na+].O.O>[NH2:50][C:36](=[O:37])[CH2:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[CH2:28][CH2:27][C:25]1[C:24]([C:39]([F:42])([F:41])[F:40])=[CH:23][N:22]=[C:21]([NH:20][C:17]2[CH:16]=[CH:15][C:14]([CH:10]3[O:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]3)=[CH:19][CH:18]=2)[N:26]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682828512-(2-(2-(2-((4-(4-(tert-Butoxycarbonyl)morpholin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

生成物 1

HCID 86675724
tert-Butyl 2-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)morpholine-4-carboxylate
収率 60.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

2-(2-(2-(2-((4-(4-(tert-Butoxycarbonyl)morpholin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid (190) (39 mg, 0.066 mmol) was dissolved in DMF (3 mL) and ammonium carbonate (38 mg, 0.40 mmol), HATU (28 mg, 0.073 mmol) and DIPEA (0.046 mL, 0.27 mmol) were added. The yellow mixture was stirred at room temperature for 18 hours then added to water (30 mL) and brine (10 mL). The mixture was extracted with ethyl acetate (3×30 mL), and the combined ethyl acetate phases washed with brine (50 mL), dried over sodium sulfate and evaporated. The residue was chromotographed (4 g deactivated* silica cartridge, 0-100% 1% isopropylamine in ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I91) (23.3 mg, 60% yield) as a colourless glass; 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 7.78 (s, 1H), 7.61 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.5 Hz, 2H), 7.31-7.19 (m, 5H, overlaps with CHCl3), 5.58 (s, 1H), 5.42 (s, 1H), 4.40 (d, J=8.5 Hz, 1H), 4.08-3.84 (m, 3H), 3.74-3.63 (m, 3H), 3.16-3.00 (m, 5H), 2.85 (s, 1H), 1.48 (s, 9H). LCMS Method C: rt 6.29 min; m/z 586.1 [M+H]+, 530.1 [M-tBu+2H]+, 608.1 [M+Na]+; m/z 584.1 [M−H]−. * cartridge deactivated by treating with 3 volumes of 1% isopropylamine in ethyl acetate followed by rinsing with a 3 volume gradient of 100-0% of 1% isopropylamine in ethyl acetate/petroleum benzine 40-60° C.

後処理

  1. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  2. washthe combined ethyl acetate phases washed with brine (50 mL)
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. custom(4 g deactivated* silica cartridge, 0-100% 1% isopropylamine in ethyl acetate/petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-c1641ab57b0e4a74bd2212d31d45cd8c
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09421205B2

反応ノート

読み込み中…

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