Cesium carbonate → HCID 67230028、化合物

HRID 1844323ノート

反応式

HRID 1844323 の反応式
Cl.Cl.[C@H:3]12[CH2:9][C@H:6]([NH:7][CH2:8]1)[CH2:5][N:4]2[C:10]([C@@:12]1([C:26]2([OH:30])[CH2:29][CH2:28][CH2:27]2)[CH2:16][CH2:15][C@@H:14]([NH:17][C@@H:18]2[C@H:23]([O:24][CH3:25])[CH2:22][O:21][CH2:20][CH2:19]2)[CH2:13]1)=[O:11].I[C:32]1[CH:37]=[N:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[N:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>O1CCOCC1.CS(C)=O.[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[NH3:4].[OH:30][C:26]1([C@:12]2([C:10]([N:4]3[CH2:5][C@@H:6]4[CH2:9][C@H:3]3[CH2:8][N:7]4[C:32]3[CH:37]=[N:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[N:33]=3)=[O:11])[CH2:16][CH2:15][C@@H:14]([NH:17][C@@H:18]3[C@H:23]([O:24][CH3:25])[CH2:22][O:21][CH2:20][CH2:19]3)[CH2:13]2)[CH2:29][CH2:28][CH2:27]1

参加物

9

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 200966762-Iodo-6-(trifluoromethyl)pyrazineHCID 67228799HCID 67228799、化合物

生成物 2

HCID 222Ammonia収率 2%HCID 67230028HCID 67230028、化合物収率 82%

試薬・触媒・溶媒 3

HCID 44556509Tris(dibenzylideneacetone) palladium触媒HCID 679Dimethyl Sulfoxide溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of 93 mg (0.20 mmol) of 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylcarbonyl]-3-(1-hydroxycyclobutyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol dihydrochloride 121 mg (0.442 mmol) of 2-iodo-6-trifluoromethylpyrazine, 326 mg (1.0 mmol) of cesium carbonate, 24 mg (40 umol) of XantPhos, and 16 mg (28 umol) of tris(dibenzylideneacetone) palladium (0) in 0.8 mL of dioxane and 0.4 mL of DMSO was heated at 80 C under argon for 18 h, then cooled and partitioned between ethyl acetate and water. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography of the residue on silica using 0-2-4% methanolic ammonia and 3% methanol in dichloromethane afforded 89 mg (82%) of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.51-2.40 (m, 16H) 2.65-2.74 (m, 1H) 3.09-3.49 (m, 10H) 3.54 (d, J=9.6 Hz, 1H) 3.61-3.80 (m, 2H) 3.88-3.96 (m, 1H) 4.06 (dd, J=12.5, 2.9 Hz, 1H) 4.96 (br. s., 1H) 5.21 (br. s., 1H) 8.02 (s, 1H) 8.15 (s, 1H). HRMS calculated for C26H36N5O4F3: 540.2797. found: 540.2896.

後処理

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-fb1be6b9523f4245909755fcb87917f3
出典データセット
uspto-grants-2015_02
特許番号
US08946413B2

反応ノート

読み込み中…