Sodium Carbonate → 5-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)thiophene-2-carboxamide

HRID 605910노트

반응식

HRID 605910 반응식
C[N:2]1CCN(C2C=CC(NC3C4N(N=CN=4)C([C:21]4[CH:22]=[C:23]([C:26]([NH2:28])=[O:27])[S:24][CH:25]=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]([O:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[CH:45][CH:44]=2)=[N:35][CH:34]=1.CC1(C)C(C)(C)OB(C2SC(C(N)=O)=CC=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[NH3:2].[O:55]1[CH2:56][CH2:57][N:52]([CH2:51][CH2:50][O: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:25]4[S:24][C:23]([C:26]([NH2:28])=[O:27])=[CH:22][CH:21]=4)=[CH:34][N:35]=3)=[CH:44][CH:45]=2)[CH2:53][CH2:54]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 575899405-(Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxamideHCID 57590052(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine

생성물 2

HCID 222AmmoniaHCID 248894665-(8-(4-(2-Morpholinoethoxy)phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)thiophene-2-carboxamide수율 25%

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-(2-morpholin-4-yl-ethoxy)-phenyl]-amine (118 mg, 0.28 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxamide (142 mg, 0.56 mmol), and Pd(PPh3)4 (81 mg, 0.07 mmol) in 1.5M Na2CO3 (1.5 mL, 2.24 mmol) and dioxane (4.5 mL). The reaction mixture is purified by silica gel column chromatography eluting with 97:3 DCM:NH3 (7M in MeOH) to yield the title compound (33 mg, 25%). LCMS: Rt 2.66 min (99%). Conversion into the mesylate salt using 0.1M methanesulfonic acid in MeOH (0.569 mL) affords the title compound (24 mg, 86%). 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.37 (3H, s, MsOH), 3.25 (2H, m), 3.50-3.64 (4H, m), 3.76 (2H, t), 4.05 (2H, d), 4.40 (2H, m), 7.09 (2H, d), 7.51 (1H, br s), 7.87 (1H, d), 7.99-8.05 (3H, m), 8.11 (1H, br s), 8.37 (1H, s), 8.84 (1H, s), 9.92 (1H, br s), 10.21 (1H, s). LCMS: Rt 1.95 min (98.8%), m/z (APCI) 466 (M+H)+.

후처리

  1. customThis compound may be prepared
  2. customThe reaction mixture is purified by silica gel column chromatography
  3. washeluting with 97:3 DCM

출처 및 근거

ORD 기록
ord-82c3aa70ad73448794aba2b3dfec8923
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915256B2

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