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Potassium Carbonate → 4-(((1R)-1-cyclopropylethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 1507918
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HRID 1507918 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]([CH:13]3[CH2:15][CH2:14]3)[CH3:12])=[C:8]([C:16]([NH2:18])=[O:17])[CH:7]=[N:6][N:5]2[CH:19]=1.[C:20]1(B(O)O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH:13]1([C@H:11]([NH:10][C:9]2[C:4]3[N:5]([CH:19]=[C:2]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:3]=3)[N:6]=[CH:7][C:8]=2[C:16]([NH2:18])=[O:17])[CH3:12])[CH2:15][CH2:14]1
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참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 68291753(R)-6-bromo-4-(1-cyclopropylethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide2회

생성물 1

HCID 682917434-(((1R)-1-cyclopropylethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide수율 49.3%

시약·촉매·용매 2

HCID 11979704
Tetrakis(triphenylphosphine)palladium
촉매
HCID 80711,2-Dimethoxyethane용매

실험 절차

A degassed solution of (R)-6-bromo-4-(1-cyclopropylethylamino) pyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 4, 20 mg, 0.062 mmol), phenylboronic acid (22.64 mg, 0.186 mmol), potassium carbonate (0.077 mL, 0.155 mmol, 2M) and palladium tetrakis(triphenylphosphine) (4.29 mg, 3.71 μmol) in DME (1 mL) was heated to 90° C. for 1 hr. The reaction mixture was concentrated and redissolved in 1 mL of MeOH, and purified by reverse-phase preparative HPLC (condition C) to yield the title compound (9.8 mg, 48%). HPLC (condition I): retention time=2.49 min. LC/MS (M+H)+=321.1. 1H NMR (500 MHz, MeOD) δ ppm 8.04 (1 H, s), 7.82 (1 H, d, J=1.7 Hz), 7.61 (1 H, d, J=1.1 Hz), 7.59 (1 H, d, J=0.8 Hz), 7.56 (1 H, s), 7.37 (2 H, t, J=7.8 Hz), 7.21-7.26 (1 H, m), 4.05 (1 H, quin, J=6.4 Hz), 1.44 (3 H, d, J=6.4 Hz), 1.08-1.17 (1 H, m), 0.52-0.62 (2 H, m), 0.35-0.41 (2 H, m).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionredissolved in 1 mL of MeOH
  3. custompurified by reverse-phase preparative HPLC (condition C)

출처 및 근거

ORD 기록
ord-799e745315b94ce999b6ccd7d3385974
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09221826B2

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