Diisopropylethylamine → HCID 118117060、化合物

HRID 1487345ノート

反応式

HRID 1487345 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])=[C:6]([C:8]2[C:9]([O:16][CH2:17][CH3:18])=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:61]1([CH2:66][C:67](O)=[O:68])[CH:65]=[CH:64][CH:63]=[N:62]1>CC(N(C)C)=O>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[O:19][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:67](=[O:68])[CH2:66][N:61]2[CH:65]=[CH:64][CH:63]=[N:62]2)=[CH:7][C:6]=1[C:8]1[C:9]([O:16][CH2:17][CH3:18])=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[CH:13]=1

参加物

6

反応物 4

HCID 81531Diisopropylethylamine2 回HCID 37174621H-Pyrazol-1-ylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 72548033HCID 72548033、化合物

生成物 1

HCID 118117060HCID 118117060、化合物収率 39%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

実験手順

A solution of Example 1G and DIPEA (0.15 M and 0.43 M in DMA, respectively, 257 μL, 0.04 mmol Example 1G (1.0 equivalent) and 0.12 mmol DIPEA (3.0 equivalents)), HATU (0.2 M in DMA, 257 μL, 0.052 mmol, 1.3 equivalents), and 2-(1H-pyrazol-1-yl)acetic acid (0.40 M in DMA, 121 μL, 0.048 mmol, 1.2 equivalents) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0 2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 100° C., and passed through the reactor at 180 μL min−1 (10 minute residence time). Upon exiting the reactor, the reaction was loaded directly into an injection loop and purified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (50 mm×21.2 mm). A gradient of acetonitrile (A) and 0.1% ammonium acetate in water (B) was used, at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6.5 min linear gradient 5-60% A, 6.5-7.0 min linear gradient 60-100% A, 7.0-8.9 min 100% A, 8.9-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A) to yield the title compound (7.33 mg, 39% yield). 1H NMR (400 MHz, DMSO-d6/D2O) δ 7.76 (d, J=2.3 Hz, 1H), 7.60-7.45 (m, 4H), 7.37-7.28 (m, 1H), 7.07-6.87 (m, 3H), 6.31 (t, J=2.1 Hz, 1H), 5.82 (s, 1H), 5.00 (s, 2H), 3.93 (q, J=6.9 Hz, 2H), 3.36 (s, 3H), 1.14 (t, J=6.9 Hz, 3H). MS (ESI) m/z 481.1 (M+H+).

後処理

  1. additionmixed through a perfluoroalkoxy mixing tube (0 2 mm inner diameter)
  2. customset at 100° C.
  3. custompassed through the reactor at 180 μL min−1 (10 minute residence time)
  4. custompurified by preparative HPLC on a Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (50 mm×21.2 mm)
  5. customwas used, at a flow rate of 30 mL/min (0-0.5 min 5% A, 0.5-6.5 min linear gradient 5-60% A, 6.5-7.0 min linear gradient 60-100% A, 7.0-8.9 min 100% A, 8.9-9.0 min linear gradient 100-5% A, 9.0-10 min 5% A)

出典と根拠

ORDレコード
ord-f69ba535aba442d399774857f407e1c5
出典データセット
uspto-grants-2016_08
特許番号
US09428514B2

反応ノート

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