Potassium Phosphate, Tribasic → HCID 178508818, compound

HRID 1910095Notes

Reaction equation

HRID 1910095 reaction equation
Br[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[NH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[N:25]([C:29](=[O:41])[CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=2)[CH2:24][CH2:23]3)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:40][C:37]([F:38])([F:39])[C:33]1[CH:32]=[C:31]([CH2:30][C:29]([N:25]2[C:26]3[C:22](=[CH:21][C:20]([C:2]4[C:10]5[C:5]([NH:6][CH:7]=[N:8][C:9]=5[NH2:11])=[N:4][CH:3]=4)=[CH:28][CH:27]=3)[CH2:23][CH2:24]2)=[O:41])[CH:36]=[CH:35][CH:34]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 54917977H-Pyrrolo(2,3-d)pyrimidin-4-amine, 5-bromo-HCID 668234855-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indole

Product 1

HCID 178508818HCID 178508818, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-amine (101 mg, 0.474 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indole (204 mg, 0.474 mmol), Pd2(dba)3 (8.68 mg, 0.00948 mmol) and K3PO4 (218 mg, 0.948 mmol) in 6 mL of dioxane and 2 mL of water in a microwave tube was degassed and backflushed with nitrogen 3×, followed by addition of tri-(t-butyl)phosphonium tetrafluoroborate (5.50 mg, 0.019 mmol). The mixture was degassed and backflushed with nitrogen 4×. The mixture was heated in an oil bath to 100° C. At 4 h, LCMS showed there was no starting material. The mixture was cooled to rt, EtOAc was added to the mixture. The top EtOAc layer was separated from the bottom layer carefully to avoid disturbance of the Pd residue. The EtOAc layer was rotavaped to dryness to give pale yellow solid. The solid was purified by flash column (Silica SF 15-24g cartridge), eluting with DCM-10% MeOH in DCM. The fractions with the product were combined and evaporated to dryness. The solid was triturated by MeOH, and the residue was filtered and dried to 5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-1H-pyrrolo[2,3-d]pyrimidin-4-amine as an off-white solid. LC/MS [M+1]+438. 1H NMR (400 MHz, DMSO-d6) δ 3.25 (t, J=8.34 Hz, 2H), 4.03 (s, 2H), 4.27 (t, J=8.46 Hz, 2H), 5.99 (s, 2H), 7.18 (d, J=2.27 Hz, 1H), 7.21-7.26 (m, 1H), 7.34 (s, 1H), 7.58-7.66 (m, 3H), 7.68 (s, 1H), 8.09-8.12 (m, 2H), 11.74 (s, 1H).

Workup

  1. customwas degassed
  2. customThe mixture was degassed
  3. temperatureThe mixture was cooled to rt
  4. additionEtOAc was added to the mixture
  5. customThe top EtOAc layer was separated from the bottom layer carefully
  6. customto give pale yellow solid
  7. customThe solid was purified by flash column (Silica SF 15-24g cartridge)
  8. washeluting with DCM-10% MeOH in DCM
  9. customevaporated to dryness
  10. customThe solid was triturated by MeOH
  11. filtrationthe residue was filtered
  12. dry with materialdried to 5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-1H-pyrrolo[2,3-d]pyrimidin-4-amine as an off-white solid

Sources & evidence

ORD record
ord-74d4b4d5b3ae4539bc2c7aec8bf36a8b
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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