Sodium Carbonate → (7S)-7-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-2-azaspiro[4.5]decan-3-one

HRID 75012Notes

Reaction equation

HRID 75012 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.Cl[C:31]1[N:36]=[C:35]([NH:37][C@H:38]2[CH2:48][CH2:47][CH2:46][C:40]3([CH2:44][NH:43][C:42](=[O:45])[CH2:41]3)[CH2:39]2)[C:34]([F:49])=[CH:33][N:32]=1.C([O-])([O-])=O.[Na+].[Na+]>C(#N)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>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:31]3[N:36]=[C:35]([NH:37][C@H:38]4[CH2:48][CH2:47][CH2:46][C:40]5([CH2:44][NH:43][C:42](=[O:45])[CH2:41]5)[CH2:39]4)[C:34]([F:49])=[CH:33][N:32]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 86667444(7S)-7-(2-chloro-5-fluoropyrimidin-4-ylamino)-2-azaspiro[4.5]decan-3-one

Product 1

HCID 68007747(7S)-7-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-2-azaspiro[4.5]decan-3-oneYield 90.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.083 g, 0.195 mmol) in acetonitrile (1.6 mL) was added (7S)-7-(2-chloro-5-fluoropyrimidin-4-ylamino)-2-azaspiro[4.5]decan-3-one (62c) (0.053 g, 0.177 mmol) and degassed under N2. Aqueous Na2CO3 (0.266 mL of 2 M solution, 0.5320 mmol) was added followed by Pd(PPh3)4 (0.031 g, 0.027 mmol). The reaction was sealed and heated in a microwave at 120° C. for 30 min then concentrated in vacuo. The material was diluted in CH2Cl2 and silica gel chromatography using a gradient of Hexanes:EtOAc then 20% MeOH in CH2Cl2. Pure fractions were combined and concentrated to give 91 mg of 62d. LCMS+: 569.26 at 4.20 min (10-90% MeOH, 3/5 grad/run, Formic Acid).

Workup

  1. customdegassed under N2
  2. customThe reaction was sealed
  3. concentrationthen concentrated in vacuo
  4. additionThe material was diluted in CH2Cl2
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-908a94b1dee34a6a84f00b12ba1af9b4
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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