Dichloromethane → Tert-butyl 4-[4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)phenyl]piperazine-1-carboxylate

HRID 1972766Notes

Reaction equation

HRID 1972766 reaction equation
Br[C:2]1[N:10]2[C:5]([C:6]([NH2:11])=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)O1.ClCCl.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]>[NH2:11][C:6]1[C:5]2=[CH:4][CH:3]=[C:2]([C:20]3[CH:21]=[CH:22][C:23]([N:26]4[CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31]4)=[CH:24][CH:25]=3)[N:10]2[N:9]=[CH:8][N:7]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27955144-(4-tert-Butoxycarbonylpiperazinyl)phenylboronic acid, pinacol esterHCID 422813837-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 58529456Tert-butyl 4-[4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)phenyl]piperazine-1-carboxylateYield 82.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (801 mg, 3.76 mmol), tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]tetrahydro-1(2H)-pyrazinecarboxylate (2.19 g, 5.64 mmol), and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II)-complex with dichloromethane (275 mg, 0.38 mmol) in degassed DME (25 mL) was added aqueous Na2CO3 solution (2 M, 5.6 mL). The reaction was heated (80° C.) for 17 h and then cooled to rt. The mixture was filtered through a pad of Celite® using ethyl acetate to rinse. The filtrate was washed with water (75 mL), dried (Na2SO4), and concentrated. The crude material was purified by ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to afford 1.22 g (74%) of the desired product as an off-white solid, which contained trace impurities. 1H NMR (300 MHz, DMSO-d6) δ 7.94-7.88 (m, 2 H), 7.86 (s, 1 H), 7.65 (br s, 2 H), 7.03-6.97 (m, 1 H), 6.94 (d, 1H), 6.89 (d, 1 H), 3.51-3.42 (m, 4 H), 3.19-3.11 (m, 4 H), 1.42 (s, 9 H); ES-MS m/z 395.1 [M+H]+, HPLC RT (min) 2.52.

Workup

  1. temperaturecooled to rt
  2. filtrationThe mixture was filtered through a pad of Celite®
  3. washto rinse
  4. washThe filtrate was washed with water (75 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by ISCO® chromatography

Sources & evidence

ORD record
ord-fc3b740613c64ecfbd533dee72f5fbd2
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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