Cesium carbonate → HCID 178476881, 화합물

HRID 511547

반응식

HRID 511547 반응식
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.[NH2:31][C:32]1[N:37]=[CH:36][C:35]([CH2:38][P:39](=[O:46])([O:43][CH2:44][CH3:45])[O:40][CH2:41][CH3:42])=[CH:34][C:33]=1[O:47][CH3:48].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]>[OH:26][C@H:23]1[CH2:24][CH2:25][C@H:20]([C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6]3[C:5]([C:27]([F:30])([F:29])[F:28])=[CH:4][N:3]=[C:2]([NH:31][C:32]4[N:37]=[CH:36][C:35]([CH2:38][P:39](=[O:46])([O:40][CH2:41][CH3:42])[O:43][CH2:44][CH3:45])=[CH:34][C:33]=4[O:47][CH3:48])[N:7]=3)=[C:17]3[C:13]=2[CH2:14][N:15]([CH3:19])[C:16]3=[O:18])[CH2:21][CH2:22]1

참가 물질

7

반응물 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]phosphonate2회HCID 178479962HCID 178479962, 화합물2회

생성물 1

HCID 178476881HCID 178476881, 화합물수율 1%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

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, 6 H), 1.45 (m, 2 H), 1.63 (m, 2 H), 1.90 (m, 2 H), 2.16 (m, 2 H), 2.50 (m, 1 H), 3.18 (d, J=21.2 Hz, 2 H), 3.22 (s, 3 H), 3.77 (m, 1 H), 3.94 (s, 3 H), 4.04-4.10 (m, 4 H), 4.39 (s, 2 H), 7.41 (d, J=8.4 Hz, 1 H), 8.04 (s, 1 H), 8.45 (s, 1 H), 9.33 (d, J=8.0 Hz, 1 H), 10.86 (s, 1 H). MS (ES+): m/z 679.23 [MH+]. HPLC: tR=1.21 min (UPLC TOF, polar—3 min).

후처리

  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)

출처 및 근거

ORD 기록
ord-5fba2aba5ad1456e9e0cc6406dc36f1e
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096624B2

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