Ethylamine → HCID 90409721, compound

HRID 589111Notes

Reaction equation

HRID 589111 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][CH:13]([C:17]4[C:18]([C:23](O)=[O:24])=[N:19][CH:20]=[CH:21][CH:22]=4)[N:12]4[C:26](=[O:28])[NH:27][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:29])[O:4][N:3]=1.[CH2:30]([NH2:32])[CH3:31].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][C@H:13]([C:17]4[C:18]([C:23]([NH:32][CH2:30][CH3:31])=[O:24])=[N:19][CH:20]=[CH:21][CH:22]=4)[N:12]4[C:26](=[O:28])[NH:27][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:29])[O:4][N:3]=1

Participants

6

Reactant 4

HCID 6341EthylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 90408827HCID 90408827, compound

Product 1

HCID 90409721HCID 90409721, compoundYield 71.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-[7-(3,5-Dimethylisoxazol-4-yl)-2-oxo-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazin-4-yl]pyridine-2-carboxylic acid (30.0 mg, 0.0764 mmol) (from step 2) in N,N-dimethylformamide (1.0 mL) was treated with ethylamine (10.8 μL, 0.191 mmol) followed by N,N-diisopropylethylamine (66.6 μL, 0.382 mmol) and stirred at room temperature for 5 min. The reaction mixture was subsequently treated with benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate [Aldrich #: 226084](50.7 mg, 0.115 mmol) and stirred at room temperature for 1 h. Purification by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (23 mg, 71%) as a single enantiomer. 1H NMR (400 MHz, DMSO-d6) δ 9.03 (t, J=5.9 Hz, 1H), 8.58 (dd, J=4.6, 1.4 Hz, 1H), 7.49 (dd, J=8.0, 4.6 Hz, 1H), 7.11 (dd, J=8.0, 1.2 Hz, 1H), 6.87 (d, J=8.0 Hz, 1H), 6.80 (d, J=8.0 Hz, 1H), 6.54-6.41 (m, 1H), 4.64-4.45 (m, 2H), 3.43-3.24 (m, 2H), 2.24 (s, 3H), 2.07 (s, 3H), 1.15 (t, J=7.2 Hz, 3H); LCMS calculated for C22H22N5O4 (M+H)+: m/z=420.2. found: 420.2.

Workup

  1. stirringstirred at room temperature for 1 h
  2. customPurification by preparative LCMS (XBridge C18 column
  3. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-26dbb2cbc57148e79a7e5cf71699022c
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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