Cesium carbonate → tert-butyl 4-[4-(7-amino-2-chloro-3-methylfuro[2,3-c]pyridin-4-yl)-1H-pyrazol-1-yl]piper-idine-1-carboxylate

HRID 389489Notes

Reaction equation

HRID 389489 reaction equation
[Cl:1][C:2]1[O:12][C:5]2=[C:6]([NH2:11])[N:7]=[CH:8][C:9](I)=[C:4]2[C:3]=1[CH3:13].CC1(C)C(C)(C)OB([C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)[CH:26]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>COCCOC.O.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]>[NH2:11][C:6]1[N:7]=[CH:8][C:9]([C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:28][CH2:29][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:31][CH2:32]3)[CH:26]=2)=[C:4]2[C:3]([CH3:13])=[C:2]([Cl:1])[O:12][C:5]=12

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 667606172-Chloro-4-iodo-3-methylfuro[2,3-c]pyridin-7-amine

Product 1

HCID 66759891tert-butyl 4-[4-(7-amino-2-chloro-3-methylfuro[2,3-c]pyridin-4-yl)-1H-pyrazol-1-yl]piper-idine-1-carboxylateYield 62%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A vial was charged with 2-chloro-4-iodo-3-methylfuro[2,3-c]pyridin-7-amine (100 mg, 0.32 mmol), tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (140 mg, 0.39 mmol), Cs2CO3(150 mg, 0.48 mmol), Pd(dppf)Cl2 (20 mg, 0.027 mmol, 8 mole %), and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (40 mg, 0.080 mmol, 26 mole %) in DME (5 mL) and H2O (0.5 mL). The vial was purged with N2 and heated at 100° C. in a microwave reactor for 1 h. Water (20 mL) was added, and the mixture was extracted with EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative TLC (EtOAc) to afford 85 mg (62%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 7.67 (s, 1H), 7.48 (s, 1H), 7.39 (s, 1H), 4.66 (s, 2H), 4.23 (m, 4H), 2.85 (m, 1H), 2.14 (m, 2H), 2.10 (m, 1H), 1.94 (s, 3H), 1.87 (m, 1H), 1.41 (s, 9H).

Workup

  1. customThe vial was purged with N2
  2. additionWater (20 mL) was added
  3. extractionthe mixture was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative TLC (EtOAc)

Sources & evidence

ORD record
ord-52c62658eecf45549fb365b548f628e7
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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