Water → 4-[2-(4-Morpholin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1262263Notes

Reaction equation

HRID 1262263 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:29]2[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)=[CH:33][CH:32]=3)=[N:28]2)=[CH:23][CH:22]=1.[C:43]([O:47][C:48]([N:50]1[CH2:55][CH:54]=[C:53](B2OC(C)(C)C(C)(C)O2)[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44].C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([C:21]2[N:29]3[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([N:37]5[CH2:38][CH2:39][O:40][CH2:41][CH2:42]5)=[CH:33][CH:32]=4)=[N:28]3)=[CH:23][CH:22]=2)[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:44])[CH3:45]

Participants

8

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 54578326(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(4-morpholin-4-yl-phenyl)-amine

Product 1

HCID 667122144-[2-(4-Morpholin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Into a 30 mL vial, Palladium Acetate (35 mg, 0.16 mmol) and Triphenylphosphine (100 mg, 0.4 mmol) were added and purged under an atmosphere of Nitrogen for 10 minutes. 1,4-Dioxane (5.9 mL) was added and stirred for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(4-morpholin-4-yl-phenyl)-amine (0.250 g, 0.668 mmol), 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.413 g, 1.34 mmol), N,N-Dimethylformamide (5.9 mL) and 1.50 M of Sodium carbonate in Water (2.47 mL, 3.70 mmol) were added and heated at 85° C. for 8 hours. The reaction was partitioned with DCM. The solid was filtered and washed with DCM. The organic solvent was removed under vacuum. The desired product was isolated via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol). The collected fractions afforded 4-[2-(4-Morpholin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-piperidine-1-carboxylic acid tert-butyl ester as a yellow solid (180, 56%). LCMS (E/I+) 477.8 (M+H). NMR 1H (DMSO-d6)-9.15 (s, 1H), 8.88 (s, 1H), 7.57 (d, 2H, J=8.75 Hz), 7.10 (bs, 1H), 6.91 (d, 2H, J=8.75 Hz), 6.82 (d, 1H, J=4.66 Hz), 6.79 (d, 1H, J=4.66 Hz), 4.12 (bs, 2H), 3.74 (t, 4H, J=4.66 Hz), 3.58 (t, 2H, J=5.25 Hz), 3.06 (t, 4H, J=5.25 Hz), 2.58 (bs, 2H), 1.44 (s, 9H).

Workup

  1. custompurged under an atmosphere of Nitrogen for 10 minutes
  2. addition1,4-Dioxane (5.9 mL) was added
  3. customThe reaction was partitioned with DCM
  4. filtrationThe solid was filtered
  5. washwashed with DCM
  6. customThe organic solvent was removed under vacuum

Sources & evidence

ORD record
ord-95d4a689ad3546d1a45fcf09e55b1059
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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