Cesium carbonate → HCID 178476881、化合物

HRID 1948119

反応式

HRID 1948119 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([C@H:20]3[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]3)=[C:13]3[C:17]=2[C:16](=[O:18])[N:15]([CH3:19])[CH2:14]3)[C:5]([C:27]([F:30])([F:29])[F:28])=[CH:4][N:3]=1.[CH2:31]([O:33][P:34]([CH2:39][C:40]1[CH:41]=[N:42][C:43]([NH2:48])=[C:44]([O:46][CH3:47])[CH:45]=1)(=[O:38])[O:35][CH2:36][CH3:37])[CH3:32].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:31]([O:33][P:34]([CH2:39][C:40]1[CH:41]=[N:42][C:43]([NH:48][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:10]=[CH:11][C:12]([C@H:20]4[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]4)=[C:13]4[C:17]=3[C:16](=[O:18])[N:15]([CH3:19])[CH2:14]4)[C:5]([C:27]([F:30])([F:29])[F:28])=[CH:4][N:3]=2)=[C:44]([O:46][CH3:47])[CH:45]=1)(=[O:38])[O:35][CH2:36][CH3:37])[CH3:32]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86654065Diethyl[(6-amino-5-methoxypyridin-3-yl)methyl]phosphonate2 回HCID 178479962HCID 178479962、化合物2 回

生成物 1

HCID 178476881HCID 178476881、化合物収率 1%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

実験手順

To a suspension of 7-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-4-(trans-4-hydroxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 308C, 130.0 mg, 0.29 mmol), diethyl[(6-amino-5-methoxypyridin-3-yl)methyl]phosphonate (Compound 308A, 80.9 mg, 0.29 mmol), Pd(OAc)2 (3.31 mg, 0.015 mmol), Xantphos (17.1 mg, 0.029 mmol), and Cs2CO3 (192.2 mg, 0.59 mmol) in dry dioxane (1.2 mL) was bubbled nitrogen for 2 min. This mixture was then irradiated at 160° C. for 40 min in a CEM microwave reactor. After cooled to room temperature, the reaction mixture was filtered and the filtrate was concentrated and purified by silica gel chromatography (1-5% MeOH in DCM) to give 1.9 mg of the title compound (yield: 1%). 1H NMR (CDCl3, 400 MHz): δ=1.29 (t, J=7.2 Hz, 6H), 1.45 (m, 2H), 1.63 (m, 2H), 1.90 (m, 2H), 2.16 (m, 2H), 2.50 (m, 1H), 3.18 (d, J=21.2 Hz, 2H), 3.22 (s, 3H), 3.77 (m, 1H), 3.94 (s, 3H), 4.04-4.10 (m, 4H), 4.39 (s, 2H), 7.41 (d, J=8.4 Hz, 1H), 8.04 (s, 1H), 8.45 (s, 1H), 9.33 (d, J=8.0 Hz, 1H), 10.86 (s, 1H). MS (ES+): m/z 679.23 [MH+]. HPLC: tR=1.21 min (UPLC TOF, polar—3 min).

後処理

  1. customwas bubbled nitrogen for 2 min
  2. customThis mixture was then irradiated at 160° C. for 40 min in a CEM microwave reactor
  3. filtrationthe reaction mixture was filtered
  4. concentrationthe filtrate was concentrated
  5. custompurified by silica gel chromatography (1-5% MeOH in DCM)

出典と根拠

ORDレコード
ord-52090e8b690d4ed9b8d2849627a77d98
出典データセット
uspto-grants-2013_03
特許番号
US08399433B2

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