Cesium carbonate → HCID 66711742, compound

HRID 1262282Notes

Reaction equation

HRID 1262282 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[N+:25]([C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH2:31][NH2:32])([O-:27])=[O:26].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:8]3[N:7]=[CH:6][C:5]4=[CH:4][CH:3]=[C:2]([NH:32][CH2:31][C:30]5[CH:33]=[CH:34][CH:35]=[C:28]([N+:25]([O-:27])=[O:26])[CH:29]=5)[N:10]4[N:9]=3)=[CH:13][CH:14]=2)[CH2:19][CH2:20]1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 1227223-NitrobenzylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66711742HCID 66711742, compound

Conditions

Temperature
120 °C

Procedure

Into a 8-dram vial, (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (66.6 mg, 0.000172 mol), 3-nitrobenzylamine (31.42 mg, 0.0002065 mol) Palladium Acetate (4.00 mg, 0.0000178 mol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (30.0 mg, 0.0518 mmol), and Cesium Carbonate (240.0 mg, 0.7366 mmol) were added. The mixture was purged with nitrogen for 15 minutes. 1,4-Dioxane (2.00 mL) was added. The reaction vessel was sealed and heated at 120° C. for 2 hours. The reaction mixture was partitioned with DCM. The solid was filtered through celite and washed with DCM. The filtrate was evaporated to give a semi-solid. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN (0 to 20% ACN). The collected fractions were lyophilized to give N(2)-[4-(4-Methyl-piperazin-1-yl)-phenyl]-N(7)-(3-nitro-benzyl)-pyrrolo[2,1-f][1,2,4]triazine-2,7-diamine a solid (32 mg, 32%). The solid was triturated with Et2O to give a yellow solid. LCMS (E/I+) 459.14 (M+H). NMR 1H (DMSO-d6)-9.75 (bs, 1H), 9.31 (s, 1H), 8.36 9 s, 1H), 8.27 (s, 1H), 8.14 (d, 1H, J=8.20 Hz), 7.86 (d, 1H, J=7.60 Hz), 7.59-7.73 (m, 3H), 7.49 (bs, 1H), 7.09 (bs, 1H), 6.98 (d, 2H, J=8.20 Hz), 6.55 (bs, 1H), 4.76 (s, 2H), 3.75 (d, 2H, J=12.89 Hz), 3.54 (d, 2H, J=11.72 Hz), 3.16 (q, 2H, J=18.79 Hz), 2.79-2.99 (m, 5H).

Workup

  1. customThe mixture was purged with nitrogen for 15 minutes
  2. addition1,4-Dioxane (2.00 mL) was added
  3. customThe reaction vessel was sealed
  4. customThe reaction mixture was partitioned with DCM
  5. filtrationThe solid was filtered through celite
  6. washwashed with DCM
  7. customThe filtrate was evaporated
  8. customto give a semi-solid
  9. customThe reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN (0 to 20% ACN)

Sources & evidence

ORD record
ord-7feb9a8431a1421b89cac2740656141b
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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