Tetrahydrofuran → HCID 11341430, compound

HRID 2099769Notes

Reaction equation

HRID 2099769 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]([NH:20][C:21]([N:23]2[CH2:28][CH2:27][CH:26]([N:29]3[CH2:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[NH:31][C:30]3=[O:39])[CH2:25][CH2:24]2)=[O:22])[CH2:9][C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([CH3:19])[CH:18]=2)[NH:15][N:14]=[CH:13]3)[CH:5]=[CH:4][CH:3]=1.O1CCC[CH2:41]1>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>[CH3:19][C:17]1[CH:18]=[C:10]([CH2:9][CH:8]([NH:20][C:21]([N:23]2[CH2:28][CH2:27][CH:26]([N:29]3[CH2:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[NH:31][C:30]3=[O:39])[CH2:25][CH2:24]2)=[O:22])[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([CH3:41])[N:7]=2)[CH:11]=[C:12]2[C:16]=1[NH:15][N:14]=[CH:13]2

Participants

4

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 11215446HCID 11215446, compound

Product 1

HCID 11341430HCID 11341430, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

A microwave tube was charged with (±)-N-(1-(6-bromopyridin-2-yl)-2-(7-methyl-1H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide (11 mg, 0.0187 mmol, 1.0 equiv), Pd(PPh3)4 (2 mg, 0.1 equiv) and anhydrous tetrahydrofuran (0.5 mL) under nitrogen. ZnMeCl (2.0 M in tetrahydrofuran, 0.12 mL, 0.24 mmol) was added via syringe resulting in gas evolution. The vial was sealed and heated by microwave at 110° C. for 4 h. Tetrahydrofuran was removed in vacuo and the residue was partitioned between ethyl acetate and concentrated ammonium hydroxide solution. The organic layer was separated and washed with brine, dried and concentrated. Flash column chromatography (10% methanol/methylene chloride) afforded the desired product (9.2 mg, 94%) as a white powder. MS (ESI) [M+H]+=524. 1H-NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.33 (br., 1H), 7.22-6.80 (m, 7H), 6.65 (d, J=8.0 Hz, 1H), 6.59 (br., 1H), 6.20 (br., 1H), 5.20-5.08 (m, 1H), 4.62-4.48 (m, 1H), 4.22 (s, 2H), 4.20-4.03 (m, 2H), 3.40-3.28 (m, 1H), 3.10-2.97 (m, 1H), 2.97-2.78 (m, 2H), 2.54 (s, 3H), 2.45 (s, 3H), 1.95-1.50 (m, 5H). HPLC tR=1.11 min.

Workup

  1. customresulting in gas evolution
  2. customThe vial was sealed
  3. customTetrahydrofuran was removed in vacuo
  4. customthe residue was partitioned between ethyl acetate and concentrated ammonium hydroxide solution
  5. customThe organic layer was separated
  6. washwashed with brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6f9c27b4590a48dfa45806fd7837b44e
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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