Methylamine → 2-(4-fluorophenyl)-2-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)-N-methylacetamide

HRID 1992146

반응식

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:12]2[CH2:17][CH2:16][C:15]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=3)([CH2:18][CH2:19][N:20]3[C@H:25]4[CH2:26][CH2:27][C@@H:21]3[CH2:22][CH:23]([N:28]3[C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=5[N:30]=[C:29]3[CH3:37])[CH2:24]4)[CH2:14][CH2:13]2)[C:9]([OH:11])=O)=[CH:4][CH:3]=1.FC1C=C(C2(CCN3[C@H]4CC[C@@H]3CC(N3C5C=CC=CC=5N=C3C)C4)CC[NH:55][CH2:54]C2)C=CC=1.FC1C=CC(B(O)O)=CC=1.CN.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:12]2[CH2:17][CH2:16][C:15]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=3)([CH2:18][CH2:19][N:20]3[C@H:21]4[CH2:27][CH2:26][C@@H:25]3[CH2:24][CH:23]([N:28]3[C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=5[N:30]=[C:29]3[CH3:37])[CH2:22]4)[CH2:14][CH2:13]2)[C:9]([NH:55][CH3:54])=[O:11])=[CH:4][CH:3]=1

참가 물질

반응물 5

HCID 6329Methylamine

HCID 2856454-Fluorophenylboronic acid

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

HCID 44573338(4-Fluorophenyl)(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)acetic acid

HCID 587288151-((1R,5S)-8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole

생성물 1

HCID 103264152-(4-fluorophenyl)-2-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)-N-methylacetamide

실험 절차

(4-Fluorophenyl)(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)acetic acid (prepared from 1-((1R,5S)-8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole and 4-fluorophenylboronic acid following the procedure outlined in example 412. (19 mg, 0.032 mmol) was coupled with methylamine (16 μL, 2M in THF) under promotion of HATU (12 mg, 0.032 mmol) The title compound was obtained as solid (12 mg, 60%) after purification by flash chromatography, eluting with a gradient of 0-10% methanol in ethyl acetate. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=7.1 Hz, 1H), 7.32-7.24 (m, 4H), 7.19-7.12 (m, 2H), 7.03-6.89 (m, 6H), 4.59 (br, 1H), 3.75 (s, 1H), 3.22 (br, 2H), 2.84 (d, J=4.9 Hz, 3H), 2.55 (s, 3H), 2.52-2.47 (m, 1H), 2.40-2.09 (m, 6H), 1.93-1.87 (m, 7H), 1.78-1.61 (m, 6H). HRMS m/z (M+H)+ calcd 612.3514, obsd 612.3530.

출처 및 근거

ORD 기록: ord-84e501dec7114380bc2b1d09c782b848
출처 데이터셋: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
특허 번호: US07645771B2

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