Methanol → (rac)-rel-[(3aR,4R,6R,6aS)-6-{[2-(3-ethynylphenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol

HRID 928254Notes

Reaction equation

HRID 928254 reaction equation
[CH3:1][C:2]1([CH3:34])[O:6][C@H:5]2[C@H:7]([NH:12][C:13]3[N:18]4[N:19]=[C:20]([C:22]5[CH:27]=[CH:26][CH:25]=[C:24]([C:28]#[C:29][Si](C)(C)C)[CH:23]=5)[CH:21]=[C:17]4[N:16]=[CH:15][CH:14]=3)[CH2:8][C@H:9]([CH2:10][OH:11])[C@H:4]2[O:3]1.C1(C#C[Si](C)(C)C)C=CC=CC=1.CO.C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>>[C:28]([C:24]1[CH:23]=[C:22]([C:20]2[CH:21]=[C:17]3[N:16]=[CH:15][CH:14]=[C:13]([NH:12][C@H:7]4[C@@H:5]5[O:6][C:2]([CH3:34])([CH3:1])[O:3][C@@H:4]5[C@@H:9]([CH2:10][OH:11])[CH2:8]4)[N:18]3[N:19]=2)[CH:27]=[CH:26][CH:25]=1)#[CH:29]

Participants

6

Reactant 5

HCID 887MethanolHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 1374641-Phenyl-2-(trimethylsilyl)acetyleneHCID 89754216(rac)-rel-{(3aR,4R,6R,6aS)-2,2-dimethyl-6-[(2-{3-[(trimethylsilyl)ethynyl]phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol

Product 1

HCID 89754375(rac)-rel-[(3aR,4R,6R,6aS)-6-{[2-(3-ethynylphenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanolYield 81.2%

Procedure

(rac)-rel-{(3aR,4R,6R,6aS)-2,2-dimethyl-6-[(2-{3-[(trimethylsilyl)ethynyl]phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol (0.067 g, 0.00014 mol; synthesized following Step 1 in Method A except using 4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylethynyl-trimethylsilane instead of 1-naphthaleneboronic acid) is dissolved in methanol (0.03 mL, 0.0007 mol). Potassium carbonate (21 mg, 0.00015 mol) is added and the solution is stirred at room temperature overnight. The reaction mixture is neutralized with saturated ammonium chloride solution and extracted with dichlormethane. The organic layer is concentrated in vacuo and purified by column chromatography (0-15% MeOH/CH2Cl2) to provide (rac)-rel-[(3aR,4R,6R,6aS)-6-{[2-(3-ethynylphenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol (0.046 g, yield 81%). LCMS: (AA) M+ 405; 1H NMR (400 MHz, DMSO) δ 8.25-8.05 (m, 4H), 7.52-7.44 (m, 2H), 7.00 (s, 1H), 6.25 (d, J=5.4 Hz, 1H), 5.25-5.17 (m, 1H), 4.59-4.48 (m, 2H), 4.27 (s, 1H), 4.16-3.99 (m, 1H), 3.65-3.44 (m, 2H), 2.48-2.38 (m, 1H), 2.28-2.19 (m, 1H), 1.87-1.72 (m, 1H), 1.46 (s, 3H), 1.24 (s, 3H).

Workup

  1. extractionextracted with dichlormethane
  2. concentrationThe organic layer is concentrated in vacuo
  3. custompurified by column chromatography (0-15% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d90b7c42b406488e8476f59a502fc97a
Source dataset
uspto-grants-2016_03
Patent number
US09290500B2

Reaction notes

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