Nitrogen → Arq-621

HRID 1517351Notes

Reaction equation

HRID 1517351 reaction equation
[Cl:1][C:2]1[C:3]([F:48])=[C:4]([CH:45]=[CH:46][CH:47]=1)[C:5]([N:7]([C@@H:22]([C:26]1[N:35]([NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:34](=[O:43])[C:33]2[C:28](=[CH:29][C:30]([Cl:44])=[CH:31][CH:32]=2)[N:27]=1)[CH2:23][C:24]#[CH:25])[CH2:8][CH2:9][CH2:10][N:11]1C(=O)C2C(=CC=CC=2)C1=O)=[O:6].N#N.NN>CO>[NH2:11][CH2:10][CH2:9][CH2:8][N:7]([C@@H:22]([C:26]1[N:35]([NH:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:34](=[O:43])[C:33]2[C:28](=[CH:29][C:30]([Cl:44])=[CH:31][CH:32]=2)[N:27]=1)[CH2:23][C:24]#[CH:25])[C:5](=[O:6])[C:4]1[CH:45]=[CH:46][CH:47]=[C:2]([Cl:1])[C:3]=1[F:48]

Participants

5

Reactant 3

HCID 947NitrogenHCID 9321HydrazineHCID 576954593-chloro-N-[(R)-1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-N-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)propyl]-2-fluoro-benzamide

Product 1

HCID 25110841Arq-621Yield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (R)-3-chloro-N-[1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-N-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-2-fluoro-benzamide (1.13 g, 1.65 mmol) in methanol (10 ml) and the solution was purged with N2. To this solution was added hydrazine (110 μl). The mixture was then stirred at room temperature and the reaction progress was monitored by HPLC/MS. The reaction mixture was then filtered and solvent was removed from the filtrate. The residue was purified by flash column to afford N-(3-amino-propyl)-3-chloro-N-[(R)-1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-2-fluoro-benzamide (708 mg, 91%) as off-white solid, M.p. 101-103° C. LCMS: m/e 552 [M+H]. 1H NMR (CDCl3): δ 8.13 (d, J=8.8 Hz, 1H), 7.83 (s, 1H), 7.45 (dd, J=4.8 and 2.0 Hz, 1H), 7.32 (m, 1H), 7.22 (t, J=8.0 Hz, 1H), 7.15 (t, J=8.0 Hz, 1H), 7.05 (t, J=8.0 Hz, 1H), 6.95 (m, 1H), 6.84 (t, J=7.2 Hz, 1H), 6.72 (d, J=7.2 Hz, 1H), 6.48 (d, J=7.2 Hz 1H), 3.62 (m, 1H), 3.48 (m, 1H), 3.28 (br, 1H), 3.14 (m, 1H), 3.02 (br, 1H), 2.59 (m, 2H), 2.30 (br, 1H), 2.02 (t, 2.4 Hz, 1H), 1.36 (m, 2H).

Workup

  1. filtrationThe reaction mixture was then filtered
  2. customsolvent was removed from the filtrate
  3. customThe residue was purified by flash column

Sources & evidence

ORD record
ord-51d7d0a390044e909766ada919e7e8d7
Source dataset
uspto-grants-2012_07
Patent number
US08232285B2

Reaction notes

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