Bromine → HCID 57812632, compound

HRID 911992Notes

Reaction equation

HRID 911992 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[C:23]4[CH:24]=[N:25][C:26]([NH2:40])=[C:27]([O:28][C@@H:29]([C:31]5[C:36]([Cl:37])=[CH:35][CH:34]=[C:33]([F:38])[C:32]=5[Cl:39])[CH3:30])[C:22]=4[O:21][CH:20]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:41]Br>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[C:23]4[CH:24]=[N:25][C:26]([NH2:40])=[C:27]([O:28][C@@H:29]([C:31]5[C:36]([Cl:37])=[CH:35][CH:34]=[C:33]([F:38])[C:32]=5[Cl:39])[CH3:30])[C:22]=4[O:21][C:20]=3[Br:41])[CH:16]=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 24408BromineHCID 57812309HCID 57812309, compound

Product 1

HCID 57812632HCID 57812632, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(4-{6-amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (400 mg, 0.68 mmol) in anhydrous DCM (10 mL) was added a solution of bromine (430 mg, 2.7 mmol) in DCM (3 mL). The resulting mixture was stirred at rt for 30 min. The mixture was quenched with sat. aq. Na2S2O3 (15 mL) and diluted with DCM (50 mL), then washed with brine (20 mL), and dried over anhydrous sodium sulfate. Evaporation afforded a yellow residue, which was purified by silica gel chromatography (Hex.-EtOAc=30:70→100% EtOAc) to give the title compound as a light-yellow solid. LC-MS (ES+): 668.01/669.99/671.97 [MH+]. 1H NMR (CDCl3, 400 MHz): δ 1.49 (s, 9H), 1.90 (d, J=6.8 Hz, 3H), 1.95-2.04 (m, 2H), 2.18-2.21 (m, 2H), 2.93 (m, 2H), 4.31-4.38 (m, 3H), 5.19 (br s, 2H), 6.54 (q, J=6.6 Hz, 1H), 7.08 (dd, J=8.8, 8.0 Hz, 1H), 7.30 (dd, J=8.8, 4.8 Hz, 1H), 7.85 (s, 1H), 7.94 (s, 1H), 8.05 (s, 1H).

Workup

  1. customThe mixture was quenched with sat. aq. Na2S2O3 (15 mL)
  2. additiondiluted with DCM (50 mL)
  3. washwashed with brine (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customEvaporation
  6. customafforded a yellow residue, which
  7. customwas purified by silica gel chromatography (Hex.-EtOAc=30:70→100% EtOAc)

Sources & evidence

ORD record
ord-c1aee08d3cfa450aa432325917077d28
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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