Sodium Carbonate → HCID 86664085, compound

HRID 1615879Notes

Reaction equation

HRID 1615879 reaction equation
Br[C:2]1[N:3]=[C:4]2[S:10][C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])=[N:8][C:5]2=[N:6][CH:7]=1.B([C:20]1[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=1)(O)O.C([O-])([O-])=O.[Na+].[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>O1CCOCC1>[CH:14]1([C:12]([NH:11][C:9]2[S:10][C:4]3[C:5]([N:8]=2)=[N:6][CH:7]=[C:2]([C:20]2[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=2)[N:3]=3)=[O:13])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 86664086HCID 86664086, compound

Product 1

HCID 86664085HCID 86664085, compoundYield 64.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of N-(6-bromothiazolo[4,5-b]pyrazin-2-yl)cyclopropanecarboxamide (1.00 g, 3.36 mmol) in dioxane (16 mL) was added 4-boronobenzoic acid (557 mg, 3.36 mmol) and 1N Na2CO3 aqueous solution (13.2 mL, 13.2 mmol). The reaction mixture was degassed using Argon gas for 20 min followed by the addition of dichlorobis(triphenylphospine) palladium(II) (141 mg, 0.20 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (128 mg, 0.30 mmol). The reaction flask was put into the preheated oil-bath at 120° C. The reaction mixture was further stirred at 120° C. for a period of 10 h after which it was filtered. 2.0 N NaOH solution was added to the filtrate until pH 10 (monitored with pH paper) and then partitioned between ethyl acetate and water. A 6.0 N aqueous HCl solution was added to the water layer until pH 6 (monitored with pH paper). The resulting brown solid was collected by filtration and dried to give 740 mg (64% yield) of 4-(2-(cyclopropanecarboxamido)thiazolo[4,5-b]pyrazin-6-yl)benzoic acid.

Workup

  1. customThe reaction mixture was degassed
  2. customfor 20 min
  3. customwas put into the preheated oil-bath at 120° C
  4. filtrationwas filtered
  5. addition2.0 N NaOH solution was added to the filtrate until pH 10 (monitored with pH paper)
  6. custompartitioned between ethyl acetate and water
  7. additionA 6.0 N aqueous HCl solution was added to the water layer until pH 6 (monitored with pH paper)
  8. filtrationThe resulting brown solid was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-a2adf271f7f84e30bbb453a761ec037b
Source dataset
uspto-grants-2014_07
Patent number
US08765747B2

Reaction notes

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