Hydrochloric Acid → HCID 66833024, compound

HRID 579501Notes

Reaction equation

HRID 579501 reaction equation
COC1C=C2C(=CC=1OC)CNCC2.C([O:17][C:18](=[O:57])[C:19]([NH:49]C(OC(C)(C)C)=O)([CH2:33][CH2:34][N:35]1[CH2:44][CH2:43][C:42]2[C:37](=[CH:38][C:39]([O:47][CH3:48])=[C:40]([O:45][CH3:46])[CH:41]=2)[CH2:36]1)[CH2:20][CH2:21][CH2:22][CH2:23][B:24]1[O:28]C(C)(C)C(C)(C)[O:25]1)C.[ClH:58]>O>[ClH:58].[ClH:58].[NH2:49][C:19]([CH2:33][CH2:34][N:35]1[CH2:44][CH2:43][C:42]2[C:37](=[CH:38][C:39]([O:47][CH3:48])=[C:40]([O:45][CH3:46])[CH:41]=2)[CH2:36]1)([CH2:20][CH2:21][CH2:22][CH2:23][B:24]([OH:28])[OH:25])[C:18]([OH:57])=[O:17]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 156236,7-Dimethoxy-1,2,3,4-TetrahydroisoquinolineHCID 66833521HCID 66833521, compound

Product 1

HCID 66833024HCID 66833024, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-Amino-6-borono-2-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]-hexanoic acid dihydrochloride is prepared in a manner analogous to that set forth in Example 16, except 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline is used as the amine in step 6. The final step is as follows: a solution of 2-tert-butoxycarbonylamino-2-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxa-borolan-2-yl)-hexanoic acid ethyl ester (108 mg) in 6 N hydrochloric acid (5 mL) was stirred at 95° C. overnight. After cooling to room temperature, the reaction mixture was transferred to a separatory funnel, diluted with deionized water (5 mL) and washed with dichloromethane (3×). The aqueous layer was frozen in liquid nitrogen and lyophilized to give the title compound as a colorless foam (66 mg); 1H NMR (D2O, 300 MHz) δ 6.75 (s, 1H), 6.66 (s, 1H), 4.39 (d, J=15 Hz, 1H), 4.14 (d, J=15 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 3H), 3.18-3.46 (m, 4H), 2.97 (m, 2H), 2.31 (t, J=8 Hz, 2H), 1.82 (m, 2H), 1.27 (m, 3H), 1.12 (m, 1H) and 0.64 (m, 2H); MS (+CI): m/z for C19H31BN2O6: expected 394.2. found 395.5 (M+H)+, 377.4 (M+H−H2O)+, 359.4 (M+H-2H2O)+.

Workup

  1. customthe reaction mixture was transferred to a separatory funnel
  2. washwashed with dichloromethane (3×)
  3. temperatureThe aqueous layer was frozen in liquid nitrogen

Sources & evidence

ORD record
ord-c6aa04312fb248aaae2a0fb62706906e
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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