Hydrochloric Acid → HCID 86706002, compound

HRID 625512Notes

Reaction equation

[CH2:1]([N:3]([CH2:68][CH3:69])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([CH:45]=[CH:46][CH:47]=2)[C:16]([N:18]([CH3:44])[CH2:19][CH2:20][N:21]([CH2:40][CH2:41][O:42][CH3:43])[CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][C:33]([O:35]C(C)(C)C)=[O:34])=[O:17])=[O:12])=[C:6]([C:48]2[CH:53]=[CH:52][C:51]([C:54](=[O:67])[NH:55][CH2:56][C:57]3[CH:62]=[CH:61][CH:60]=[C:59]([C:63]([F:66])([F:65])[F:64])[CH:58]=3)=[CH:50][N:49]=2)[CH:5]=1)[CH3:2].Cl>>[CH2:68]([N:3]([CH2:1][CH3:2])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([CH:45]=[CH:46][CH:47]=2)[C:16]([N:18]([CH3:44])[CH2:19][CH2:20][N:21]([CH2:40][CH2:41][O:42][CH3:43])[CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:17])=[O:12])=[C:6]([C:48]2[CH:53]=[CH:52][C:51]([C:54](=[O:67])[NH:55][CH2:56][C:57]3[CH:62]=[CH:61][CH:60]=[C:59]([C:63]([F:64])([F:66])[F:65])[CH:58]=3)=[CH:50][N:49]=2)[CH:5]=1)[CH3:69]

Participants

Reactant 2

HCID 313Hydrochloric Acid

HCID 86706003HCID 86706003, compound

Product 1

HCID 86706002HCID 86706002, compound

Procedure

tert-Butyl 3-[2-[2-[2-[2-[[3-[[4-(diethylamino)-2-[5-[[3-(trifluoromethyl)phenyl]methylcarbamoyl]-2-pyridyl]phenyl]carbamoyl]benzoyl]-methyl-amino]ethyl-(2-methoxyethyl)amino]ethoxy]ethoxy]ethoxy]propanoate (0.101 g, 0.105 mmol) Example 336 and hydrochloric acid (4N in dioxane, 3 mL) were stirred for 4 hours at room temperature and then evaporated to give the carboxylic acid, 3-[2-[2-[2-[2-[[3-[[4-(diethylamino)-2-[5-[[3-(trifluoromethyl)phenyl]methylcarbamoyl]-2-pyridyl]phenyl]carbamoyl]benzoyl]-methyl-amino]ethyl-(2-methoxyethyl)amino]ethoxy]ethoxy]ethoxy]propanoic acid, as a white solid. DIEA (0.091 mL, 0.525 mmol) was added to a mixture of the acid, tert-butylamine (7.65 mg, 0.105 mmol) and HATU (48 mg, 0.126 mmol) in DMF (1 mL) and the reaction stirred for 2 hours at room temperature. The reaction was diluted with water and extracted with ethyl acetate. The extract was washed with water and brine, dried (MgSO4), and evaporated. The residue was purified by PTLC (10% methanol/20% ethyl acetate/dichloromethane) to give product as an orange foam (30 mg, 30%); MS (ES, m/z): 966 [M+H]+; NMR (400 MHz, DMSO-d6, ppm): δ 11.8 (m, 1H); 9.53 (m, 1H); 8.85 (d, J=5.2 Hz, 1H); 8.23 (m, 1H); 8.06 (m, 1H); 7.91 (m, 1H); 7.86 (s, 1H); 7.81 (m, 1H); 7.70 (m, 1H); 7.54-7.66 (m, 5H); 7.37 (m, 1H); 7.06 (d, J=2.8 Hz, 1H); 6.86 (dd, J=2.8 and 9.2 Hz, 1H); 4.61 (d, J=6.0 Hz, 2H); 3.36-3.56 (m, 15H); 3.22 (m, 3H); 3.14 (m, 1H); 3.06 (m, 2H); 3.01 (m, 2H); 2.92 (m, 2H); 2.72 (m, 2H); 2.60 (m, 1H); 2.40 (m, 2H); 2.23 (m, 2H); 1.21 (s, 9H); 1.12 (t, J=6.8 Hz, 6H).

Workup

customevaporated

Sources & evidence

ORD record: ord-cdb934818e0c4c3c81a77f43e0fcc8b8
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09301951B2

Reaction notes

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