Hydrochloric Acid → HCID 21018400, compound

HRID 1766049Notes

Reaction equation

HRID 1766049 reaction equation
[Br:1][C:2]1[C:3](=[O:35])[N:4]([CH2:19][C@@H:20]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:21][O:22]C2CCCCO2)[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8].Cl>CO>[Br:1][C:2]1[C:3](=[O:35])[N:4]([CH2:19][C@@H:20]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:21][OH:22])[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 21018398HCID 21018398, compound

Product 1

HCID 21018400HCID 21018400, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the THP protected alcohol (0.945 g, 4 mmol) in THF was added 4d.1 (1.311 g, 1.0 eq), followed by addition of Ph3P (1.311 g, 1.25 eq) and di-tert butyl azodicarboxylate (1.15 g, 1.25 eq). The mixture was stirred at room temperature overnight. The mixture was then concentrated and purified by flash column chromatography to give 5-bromo-1-[2,6-difluorobenzyl]-3-{3-(2-tetrahydro-2H-pyranyloxy)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione [MS (CI) m/z 464.9 & 466.9 (MH+-THP); tR=2.782 (method 4)]. 5-Bromo-1-[2,6-difluorobenzyl]-3-{3-(2-tetrahydro-2H-pyranyloxy)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione (110 mg) was treated with 1N HCl (10 mL)/MeOH (10 mL) at room temperature for 1 hour. The reaction mixture was concentrated and purified by prep TLC plate to yield 5-bromo-1-[2,6-difluorobenzyl]-3-{3-hydroxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione. MS (CI), m/z 464.9 & 466.9 (MH+); tR=2.613 (method 4). Suzuki coupling with 2-fluoro-3-methoxyphenylboronic acid by the procedure of Step 8B gave compound 8b.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by prep TLC plate

Sources & evidence

ORD record
ord-b08b23102e3c45e5a2c6e239dd375948
Source dataset
uspto-grants-2007_06
Patent number
US07229995B2

Reaction notes

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