Sodium Carbonate → {3-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-benzyl}-carbamic acid tert-butyl ester

HRID 1972759Notes

Reaction equation

HRID 1972759 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([C:19]([NH2:24])=[N:20][CH:21]=[N:22]3)=[C:17](Br)[CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:27]([N:34]1[CH:42]=[C:41]2[C:36]([CH:37]=[C:38](B3OC(C)(C)C(C)(C)O3)[CH:39]=[CH:40]2)=[N:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:26])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([C:19]([NH2:24])=[N:20][CH:21]=[N:22]3)=[C:17]([C:38]3[CH:39]=[CH:40][C:41]4[C:36]([CH:37]=3)=[N:35][N:34]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:42]=4)[CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 71134129[3-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzyl]-carbamic acid tert-butyl ester

Product 1

HCID 71134075{3-[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-benzyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of [3-(4-amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzyl]-carbamic acid tert-butyl ester (2.65 g, 6.1 mmol) in DMF (20 mL), 2-benzyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (3.26 g, 9.8 mmol), Pd(PPh3)4 (700 mg, 0.6 mmol) and 2 N Na2CO3 (12 mL) were added. The mixture was degassed for 20 min and was then heated to 150° C. in microwave reactor for 10 min. After cooling, the mixture was partitioned between EtoAc/H2O and the organic layer was separated and dried. Biotage® chromatography (50-100% EtOAc) provided the title product as off white solid 2.6 g (76%). NMR (300 MHz, DMSO-d6) δ 8.80 (s, 1 H), 8.05 (d, 2 H), 8.0 (s, 1 H), 7.90 (d, 1 H), 7.70 (s, 1 H), 7.60-7.40 (m, 7 H), 7.25 (d, 1 H), 7.20 (s, 1 H), 5.70 (s, 2 H), 4.10 (d, 2 H), 0.9 (s, 9 H); ES-MS m/z 561.34 [M+H]+, HPLC RT (min) 4.06.

Workup

  1. customThe mixture was degassed for 20 min
  2. temperatureAfter cooling
  3. customthe mixture was partitioned between EtoAc/H2O
  4. customthe organic layer was separated
  5. customdried

Sources & evidence

ORD record
ord-61171f35b5f14e10b1e7c5b0e6a2dfbf
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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