Sodium Carbonate → 2-(4-Cyclopentyloxy-6-methyl-5-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-2-yl)-6-fluoro-phenyl-propan-1-ol

HRID 251652Notes

Reaction equation

HRID 251652 reaction equation
[F:1][C:2]1[C:3]([CH:11]([OH:14])[CH2:12][CH3:13])=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].Cl[C:22]1[N:27]=[C:26]([CH3:28])[C:25]([CH2:29][N:30]([CH3:41])[C@@H:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34][CH2:33][CH2:32]2)=[C:24]([O:42][CH:43]2[CH2:47][CH2:46][CH2:45][CH2:44]2)[CH:23]=1>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>[CH:43]1([O:42][C:24]2[C:25]([CH2:29][N:30]([CH3:41])[CH:31]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[CH2:34][CH2:33][CH2:32]3)=[C:26]([CH3:28])[N:27]=[C:22]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=3[CH:11]([OH:14])[CH2:12][CH3:13])[CH:23]=2)[CH2:44][CH2:45][CH2:46][CH2:47]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 580898533-Fluoro-2-(1-hydroxypropyl)phenylboronic acidHCID 86593987(S)-(6-chloro-4-cyclopentyloxy-2-methyl-pyridin-3-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine

Product 1

HCID 596780542-(4-Cyclopentyloxy-6-methyl-5-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-2-yl)-6-fluoro-phenyl-propan-1-ol

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

3-Fluoro-2-(1-hydroxypropyl)phenylboronic acid (81 mg, 0.43 mmol), Na2CO3 (126 mg, 1.2 mmol) and Pd(PPh3)4 (10 mg) are added to a degassed solution (toluene 5 mL, H2O 21.6 mL and EtOH 0.8 mL) of (S)-(6-chloro-4-cyclopentyloxy-2-methyl-pyridin-3-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)amine (prepared as described in Example 43) (150 mg, 0.39 mmol) at room temperature. The mixture is heated to 100° C. for 14 hours. The organic layer is separated and the aqueous layer is extracted with DCM (2×10 mL). The combined organic layers are washed with brine, dried, and evaporated in vacuo to give crude product. The crude product is purified by PTLC and eluted with 2% MeOH in DCM to give 1-[2-(4-cylopentyloxy-6-methyl-5-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]methyl}-pyridin-2-yl)-6-fluoro-phenyl]-propan-1-ol.

Workup

  1. customThe organic layer is separated
  2. extractionthe aqueous layer is extracted with DCM (2×10 mL)
  3. washThe combined organic layers are washed with brine
  4. customdried
  5. customevaporated in vacuo
  6. customto give crude product
  7. customThe crude product is purified by PTLC
  8. washeluted with 2% MeOH in DCM

Sources & evidence

ORD record
ord-58dd644db62f4711bd81475a5dc42d65
Source dataset
uspto-grants-2011_01
Patent number
US07863454B2

Reaction notes

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