4-Methylmorpholine → 1-[5-(5-fluoro-2-{1-[2-(4-methyl-1,4-diazepan-1-yl)-2-oxoethyl]-1H-pyrazol-4-yl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,3-thiazol-2-yl]cyclobutanol

HRID 2362690ノート

反応式

HRID 2362690 の反応式
[F:1][C:2]1[C:3]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17](O)=[O:18])[CH:15]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[CH3:30][N:31]1[CH2:37][CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CS(C)=O>[F:1][C:2]1[C:3]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]([N:34]4[CH2:35][CH2:36][CH2:37][N:31]([CH3:30])[CH2:32][CH2:33]4)=[O:18])[CH:15]=3)[NH:8][C:5]2=[N:6][CH:7]=1

参加物

8

反応物 5

HCID 79724-MethylmorpholineHCID 2283491-MethylhomopiperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 670037172-(4-(5-fluoro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-pyrazol-1-yl)acetic acid

生成物 1

HCID 546730971-[5-(5-fluoro-2-{1-[2-(4-methyl-1,4-diazepan-1-yl)-2-oxoethyl]-1H-pyrazol-4-yl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,3-thiazol-2-yl]cyclobutanol

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 2-(4-(5-fluoro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-pyrazol-1-yl)acetic acid (Example 65B) (100 mg, 0.242 mmol) in N,N-dimethylformamide (783 μl) was added 1-methyl-1,4-diazepane (35.9 mg, 0.314 mmol), 4-methylmorpholine (80 μl, 0.726 mmol), 1-hydroxybenzotriazole hydrate (55.6 mg, 0.363 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (69.6 mg, 0.363 mmol). The reaction was cooled to room temperature and diluted with dimethyl sulfoxide (1 mL). The resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 um column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid) to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 12.29 (bs, 1H), 8.43 (s, 1H), 8.29 (s, 1H), 8.20 (d, J=3.6 Hz, 1H), 8.10 (s, 1H), 7.05 (s, 1H), 6.65 (s, 1H), 5.22-5.17 (m, 2H), 3.67-3.41 (m, 4H), 2.67-2.34 (m, 6H), 2.32-2.23 (m, 3H), 2.05-1.71 (m, 4H); MS ESI(+) m/z 510.1 [M+H]+.

後処理

  1. customThe resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 um column
  2. washeluting with a gradient of 5% B in A to 75% B in A over 25 minutes

出典と根拠

ORDレコード
ord-b8acefd9ad42471fbff6b8718ae54708
出典データセット
uspto-grants-2014_04
特許番号
US08691810B2

反応ノート

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