Methylamine → HCID 86679019, compound

HRID 2203381Notes

Reaction equation

HRID 2203381 reaction equation
C1COCC1.Br[C:7]1[C:8]2[C:33]([CH3:40])([C:34]3[O:35][C:36]([CH3:39])=[N:37][N:38]=3)[C:32](=[O:41])[NH:31][C:9]=2[N:10]=[C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH2:22][CH2:23][C:24]([F:30])([F:29])[C:25]([F:28])([F:27])[F:26])[N:14]=2)[N:12]=1.[CH3:42][NH2:43]>CO>[CH3:40][C:33]1([C:34]2[O:35][C:36]([CH3:39])=[N:37][N:38]=2)[C:8]2[C:7]([NH:43][CH3:42])=[N:12][C:11]([C:13]3[C:21]4[C:16](=[N:17][CH:18]=[CH:19][CH:20]=4)[N:15]([CH2:22][CH2:23][C:24]([F:29])([F:30])[C:25]([F:26])([F:28])[F:27])[N:14]=3)=[N:10][C:9]=2[NH:31][C:32]1=[O:41]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 86679020HCID 86679020, compound

Product 1

HCID 86679019HCID 86679019, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a THF solution (9 mL) of the intermediate from Step A above (116 mg, 0.202 mmol) was added a 2 M methanol solution of methylamine (0.809 mL, 1.619 mmol) and the resultant mixture heated at 140° C. under microwave irradiation for 1 hour. Purification by silica gel column chromatography using DCM/MeOH (with 0.5% NH4OH) gradient provided the title compound. Chiral separation using SFC on a Chiralcel OD column provided both enantiomers of the title compound. 1H NMR (500 MHz, DMSO-d6): δ 11.52 (1H, s), 8.90-8.86 (1H, m), 8.66-8.64 (1H, m), 7.42 (1H, dd, J=8.08, 4.49 Hz), 6.77 (1H, d, J=5.11 Hz), 4.90 (2H, t, J=6.81 Hz), 3.05-2.92 (5H, m), 1.86 (3H, s). 1H NMR δ (ppm) (DMSO-d6 with added D2O): 8.86 (1H, d, J=8.14 Hz), 8.60 (1H, d, J=4.35 Hz), 7.40 (1H, dd, J=8.09, 4.54 Hz), 4.88 (2H, t, J=6.46 Hz), 2.99-2.85 (5H, m), 2.45 (3H, s), 1.81 (3H, s). m/z=524.1 (M+H).

Workup

  1. customPurification by silica gel column chromatography

Sources & evidence

ORD record
ord-af99356b49ca472f8dfc520e46b9a9db
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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