Triphenylphosphine → 4-((3R,4R)-4-(3-bromo-4-((4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)phenoxy)-3-methylpiperidin-1-yl)-5-chloro-2-methoxypyridine

HRID 2278696Notes

Reaction equation

HRID 2278696 reaction equation
ClC1C=CC(OC)=NC=1.[Br:10][C:11]1[CH:12]=[C:13]([OH:36])[CH:14]=[CH:15][C:16]=1[N:17]1[C@@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@H:20]([CH3:31])[C:19]([C:32]([F:35])([F:34])[F:33])=[N:18]1.[Cl:37][C:38]1[C:39]([N:46]2[CH2:51][CH2:50][C@H:49](O)[C@H:48]([CH3:53])[CH2:47]2)=[CH:40][C:41]([O:44][CH3:45])=[N:42][CH:43]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>C1COCC1>[Br:10][C:11]1[CH:12]=[C:13]([CH:14]=[CH:15][C:16]=1[N:17]1[C@@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@H:20]([CH3:31])[C:19]([C:32]([F:33])([F:34])[F:35])=[N:18]1)[O:36][C@@H:49]1[CH2:50][CH2:51][N:46]([C:39]2[C:38]([Cl:37])=[CH:43][N:42]=[C:41]([O:44][CH3:45])[CH:40]=2)[CH2:47][C@H:48]1[CH3:53]

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 47382765-Chloro-2-methoxypyridineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 86719424(3R,4S)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-olHCID 867194413-bromo-4-((4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)phenol

Product 1

HCID 867194404-((3R,4R)-4-(3-bromo-4-((4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)phenoxy)-3-methylpiperidin-1-yl)-5-chloro-2-methoxypyridineYield 90.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A3E. 4-((3R,4R)-4-(3-Bromo-4(4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)phenoxy)-3-methylpiperidin-1-yl)-5-chloro-2-methoxypyridine: To a stirred solution of 3-bromo-4-((4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)phenol (10.2 mg, 0.022 mmol), (3R,4S)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-ol (81I, 11 mg, 0.042 mmol) and triphenylphosphine (13 mg, 0.049 mmol) in THF (0.2 mL) at rt was added di-tert-butylazodicarboxylate (11 mg, 0.047 mmol). The resulting solution was stirred at rt for 59 h and then evaporated The residue was chromatographed (SiO2, 96/4 CHCl3/Ether) to afford 4-((3R,4R)-4-(3-bromo-4-((4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)phenoxy)-3-methylpiperidin-1-yl)-5-chloro-2-methoxypyridine (14 mg, 66% yield) as a colorless oil: LC-MS [M+H] 705, 707, 709.

Workup

  1. customevaporated The residue
  2. customwas chromatographed (SiO2, 96/4 CHCl3/Ether)

Sources & evidence

ORD record
ord-c26aad28edfe485fa0e794b88e157042
Source dataset
uspto-grants-2015_09
Patent number
US09133163B2

Reaction notes

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