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Triethylamine → (2R)-5-{3-[(8R)-8-(3,5-Difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]prop-1-yn-1-yl}-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 1615852
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인쇄 미리보기

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HRID 1615852 반응식
[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:23])[N:18]([CH2:19][C:20]#[CH:21])[C:17](=[O:22])[C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.Br[C:25]1[CH:26]=[C:27]2[C:40](=[CH:41][CH:42]=1)[CH2:39][C@:29]1([C:37]3[C:32](=[N:33][CH:34]=[CH:35][CH:36]=3)[NH:31][C:30]1=[O:38])[CH2:28]2.C(N(CC)CC)C>CN(C=O)C.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.[Cu]I>[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:23])[N:18]([CH2:19][C:20]#[C:21][C:25]3[CH:26]=[C:27]4[C:40](=[CH:41][CH:42]=3)[CH2:39][C@:29]3([C:37]5[C:32](=[N:33][CH:34]=[CH:35][CH:36]=5)[NH:31][C:30]3=[O:38])[CH2:28]4)[C:17](=[O:22])[C:12]3([CH2:13][CH2:14][CH2:15][CH2:16]3)[NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1
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참가 물질

7

반응물 3

HCID 8471TriethylamineHCID 58118675(2R)-5-bromo-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-oneHCID 86650289(8R)-8-(3,5-Difluorophenyl)-8-methyl-9-prop-2-yn-1-yl-6,9-diazaspiro[4.5]decan-10-one

생성물 1

HCID 44468573(2R)-5-{3-[(8R)-8-(3,5-Difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]prop-1-yn-1-yl}-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매
HCID 178418397HCID 178418397, 화합물촉매
HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

A suspension of (8R)-8-(3,5-difluorophenyl)-8-methyl-9-prop-2-yn-1-yl-6,9-diazaspiro[4.5]decan-10-one from Step A (25 mg, 0.079 mmol), (R)-5-bromo-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (25 mg, 0.079 mmol described in intermediate 12 tetrakis(triphenylphosphine)palladium(0) (4.5 mg, 0.0039 mmol), copper(I)iodide (3.0 mg, 0.016 mmol), and triethylamine (0.022 mL, 0.16 mmol) in degassed DMF (0.5 ml) was heated at 80° C. for 16 hour. The mixture was filtered and purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The desired fractions were concentrated in vacuo to yield the title compound. MS: m/z=553 (M+1). HRMS: m/z=553.2400; calculated m/z=553.2410 for C33H31F2N4O2.

후처리

  1. filtrationThe mixture was filtered
  2. custompurified directly by HPLC
  3. washeluting with a gradient of H2O
  4. concentrationThe desired fractions were concentrated in vacuo

출처 및 근거

ORD 기록
ord-f52c0d44031541deb97a87cb580e4cc7
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08765759B2

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