Hydrochloric Acid → HCID 67442004, compound

HRID 1253575Notes

Reaction equation

HRID 1253575 reaction equation
C([O:5]C([NH:8][C@@H:9]([CH:53]([CH3:55])[CH3:54])[C:10]([O:12][CH2:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:24]=[N:25][C:26]([C:29]3[S:37][C:36]4[C:31](=[N:32][CH:33]=[CH:34][C:35]=4[O:38][C:39]4[CH:44]=[CH:43][C:42]([NH:45][C:46]([NH:48][CH:49]5[CH2:51][CH2:50]5)=[O:47])=[CH:41][C:40]=4[F:52])[CH:30]=3)=[CH:27][CH:28]=2)[CH2:18][CH2:17]1)=[O:15])=[O:11])=O)(C)(C)C.Cl>C(Cl)Cl.CO.C(Cl)Cl>[OH-:5].[NH4+:8].[NH2:8][C@@H:9]([CH:53]([CH3:55])[CH3:54])[C:10]([O:12][CH2:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:24]=[N:25][C:26]([C:29]3[S:37][C:36]4[C:31](=[N:32][CH:33]=[CH:34][C:35]=4[O:38][C:39]4[CH:44]=[CH:43][C:42]([NH:45][C:46]([NH:48][CH:49]5[CH2:50][CH2:51]5)=[O:47])=[CH:41][C:40]=4[F:52])[CH:30]=3)=[CH:27][CH:28]=2)[CH2:18][CH2:17]1)=[O:15])=[O:11]

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 67441681HCID 67441681, compound

Product 2

HCID 14923Ammonium HydroxideYield 2%HCID 67442004HCID 67442004, compoundYield 121%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A suspension of the Boc-valine ester 74-A (151 mg, 0.195 mmol) and a solution of HCl (0.49 ml, 1.95 mmol, 4M in 1,4-dioxane) in anhydrous DCM (10 ml) was stirred at rt for 2.5 h. The reaction mixture was concentrated and diluted with a saturated aqueous solution of sodium bicarbonate. The aqueous solution was extracted with DCM containing traces of methanol. The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by Biotage (Silia Flash 12 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 1/99 to 15/85 over 20 CV, then 15/85 to 20/80 over 10 CV), to afford the desired product 80 (80 mg, 0.118 mmol, 60% yield) as an off-white sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): mixture of rotamers, 8.73 (s, 1H), 8.58 (bd, J=1.4 Hz, 1H), 8.52 (d, J=5.3 Hz, 1H), 8.34 (s, 1H), 8.26 (dd, J=8.1, 0.7 Hz, 1H), 7.88 (dd, J=8.2, 2.2 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 7.20 (dd, J=9.0, 1.4 Hz, 1H), 6.65 (dd, J=5.3, 0.8 Hz, 1H), 6.59 (bd, J=2.5 Hz, 1H), 4.84 (d, J=14.7 Hz, 1H), 4.77 (d, J=14.9 Hz, 1H), 3.63-3.58 (m, 2H), 3.50-3.37 (m, 4H), 3.20 (d, J=5.1 Hz, 1H), 2.59-2.51 (m, 1H), 2.47-2.33 (m, 4H), 2.00-1.60 (m, 3H), 0.92 (d, J=6.8 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 0.72-0.58 (m, 2H), 0.50-0.36 (m, 2H). MS (m/z): 577.6 and 676.7 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with a saturated aqueous solution of sodium bicarbonate
  3. extractionThe aqueous solution was extracted with DCM containing traces of methanol
  4. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Biotage (Silia Flash 12 g cartridge

Sources & evidence

ORD record
ord-d81a6e221e4d46fb829cb855499cd78d
Source dataset
uspto-grants-2013_06
Patent number
US08455484B2

Reaction notes

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