Sodium Carbonate → 4-(8-(4-Morpholinophenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)furan-2-carboxamide

HRID 605917

반응식

HRID 605917 반응식
C[N:2]1CCN(C2C=CC(NC3C4N(N=CN=4)C(C4C=C(C(N)=O)SC=4)=CN=3)=CC=2)CC1.Br[C:33]1[N:38]2[N:39]=[CH:40][N:41]=[C:37]2[C:36]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[CH:45][CH:44]=2)=[N:35][CH:34]=1.CC1(C)C(C)(C)OB([C:63]2[CH:64]=[C:65]([C:68]([NH2:70])=[O:69])[O:66][CH:67]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[NH3:2].[O:52]1[CH2:53][CH2:54][N:49]([C:46]2[CH:47]=[CH:48][C:43]([NH:42][C:36]3[C:37]4[N:38]([N:39]=[CH:40][N:41]=4)[C:33]([C:63]4[CH:64]=[C:65]([C:68]([NH2:70])=[O:69])[O:66][CH:67]=4)=[CH:34][N:35]=3)=[CH:44][CH:45]=2)[CH2:50][CH2:51]1

참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 57589931(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-ylphenyl)amineHCID 575899904-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)furan-2-carboxamide

생성물 2

HCID 222AmmoniaHCID 575899894-(8-(4-Morpholinophenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)furan-2-carboxamide수율 65%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

This compound may be prepared using methods as described for Compound 6, step 4, using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-yl-phenyl)-amine (78 mg, 0.16 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-furan-2-carboxylic acid amide (100 mg, 0.34 mmol), and Pd(PPh3)4 (60 mg, 0.052 mmol) in 1.5M Na2CO3 (aq) (1.1 mL, 1.68 mmol), and dioxane (3 mL). The reaction mixture is partitioned between water and ethyl acetate, the title compound precipitates and is collected by filtration. Purification of the solid by silica gel column chromatography, eluting with DCM and 95:5 DCM:NH3 (7M in MeOH), affords the title compound (42 mg, 65%). Conversion into the mesylate salt using 0.1M methanesulfonic acid (0.82 mL) gives a solid which is triturated with diethyl ether to afford the title compound (30.5 mg). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.19 (3H, s, MsOH), 3.03-3.07 (4H, m), 3.67 (4H, m), 6.99 (2H, br s), 7.43 (1H, d), 7.74-7.82 (4H, m), 8.06 (1H, br s), 8.59 (1H, br s), 8.64 (1H, s), 9.91 (1H, br s). LCMS: Rt 2.64 min (98.1%), m/z (APCI) 406 (M+H)+.

후처리

  1. customThis compound may be prepared
  2. customThe reaction mixture is partitioned between water and ethyl acetate
  3. customthe title compound precipitates
  4. filtrationis collected by filtration
  5. customPurification of the solid by silica gel column chromatography
  6. washeluting with DCM and 95:5 DCM

출처 및 근거

ORD 기록
ord-4381d1274ff54d51b24c1325327b7155
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915256B2

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