Acetyl chloride → HCID 90409243, compound

HRID 589117Notes

Reaction equation

HRID 589117 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].F[C:9](F)(F)[C:10](O)=[O:11].[NH2:15][CH2:16][C:17]1[CH:18]=[C:19]([C:36]2[C:37]([CH3:42])=[N:38][O:39][C:40]=2[CH3:41])[C:20]2[O:25][CH2:24][C@H:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[N:22]3[C:32](=[O:35])[NH:33][C:34]=1[C:21]=23.C(N(CC)C(C)C)(C)C.C(Cl)(=O)C>C(Cl)Cl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:42][C:37]1[C:36]([C:19]2[C:20]3[O:25][CH2:24][C@H:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)[N:22]4[C:32](=[O:35])[NH:33][C:34]([C:21]=34)=[C:17]([CH2:16][NH:15][C:10](=[O:11])[CH3:9])[CH:18]=2)=[C:40]([CH3:41])[O:39][N:38]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 90409377HCID 90409377, compound

Product 1

HCID 90409243HCID 90409243, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (4S)-9-(aminomethyl)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one bis(trifluoroacetate) (10.0 mg, 0.0265 mmol) in methylene chloride (1.00 mL) was treated with N,N-diisopropylethylamine (13.8 μL, 0.0795 mmol) followed by acetyl chloride (2.26 μL, 0.0318 mmol) and stirred at room temperature for 1 h. The reaction mixture was concentrated to give a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at a flow rate of 60 mL/min) gave the desired product (9 mg, 81%) as a single enantiomer. 1H NMR (500 MHz, DMSO-d6) δ 10.89 (s, 1H), 8.52 (d, J=4.1 Hz, 1H), 8.31 (dd, J=5.7, 5.7 Hz, 1H), 7.79 (ddd, J=7.7, 7.7, 1.8 Hz, 1H), 7.41-7.27 (m, 1H), 7.14 (d, J=7.9 Hz, 1H), 6.70 (s, 1H), 5.53 (dd, J=2.4, 2.4 Hz, 1H), 4.76 (dd, J=11.5, 2.0 Hz, 1H), 4.41 (dd, J=11.5, 3.1 Hz, 1H), 4.32 (d, J=5.8 Hz, 2H), 2.22 (s, 3H), 2.05 (s, 3H), 1.87 (s, 3H); LCMS calculated for C22H22N5O4 (M+H)+: m/z=420.2. found: 420.0.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give a crude residue
  3. customPurification via preparative LCMS (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at a flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-3778194a86ac4477a891906108a33d37
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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