Dichloromethane → HCID 67294734, compound

HRID 2369000Notes

Reaction equation

HRID 2369000 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH2:43][CH:42]3[N:44]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH:38]([CH2:39][O:40][CH2:41]3)[CH:37]=2)O1.B(O)O.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C.O>[CH3:14][Si:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][O:10][CH2:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]1[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=[C:2]([C:36]2[CH2:37][CH:38]3[N:44]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH:42]([CH2:41][O:40][CH2:39]3)[CH:43]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 772312195-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amineHCID 178451395HCID 178451395, compound

Product 1

HCID 67294734HCID 67294734, compoundYield 87.5%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-chloro-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (1.01 g, 2.35 mmol) in DME (18 mL) was treated with boronate tert-butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-oxa-9-azabicyclo[3.3.1]non-6-ene-9-carboxylate (910 mg, 2.59 mmol), Pd(dppf)Cl2.CH2Cl2 (191 mg, 0.24 mmol), 2M aqueous Na2CO3 (9.1 mL) under argon and heated at 100° C. for 16 h. Upon cooling, water (50 mL) and ethyl acetate (70 mL) was added. Two layers were separated and organic layer was collected. Aqueous layer was then extracted with ethyl acetate (2×70 mL). Combined organic layer was washed with brine (1×150 mL), dried (Na2SO4) and evaporated under reduced pressure to give crude material which was purified by column chromatography (0-40% hexane-ethyl acetate) to provide the desired product tert-butyl 7-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)-3-oxa-9-azabicyclo[3.3.1]non-6-ene-9-carboxylate (1.27 g). HPLC-MS tR=3.09 min (UV254 nm). Mass calculated for formula C30H51N5O5Si2 617.3; observed MH+ (LCMS) 618.2 (m/z).

Workup

  1. temperatureUpon cooling
  2. customTwo layers were separated
  3. customorganic layer was collected
  4. extractionAqueous layer was then extracted with ethyl acetate (2×70 mL)
  5. washCombined organic layer was washed with brine (1×150 mL)
  6. dry with materialdried (Na2SO4)
  7. customevaporated under reduced pressure
  8. customto give crude material which
  9. customwas purified by column chromatography (0-40% hexane-ethyl acetate)

Sources & evidence

ORD record
ord-df387c925e504823a813a76ce875152f
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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