Dimethylformamide → HCID 59239414, compound

HRID 1698035Notes

Reaction equation

HRID 1698035 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[CH2:29][CH3:30])[C:16]3[CH2:22][CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].CN(C)C=O.C(N(CC)C(C)C)(C)C.[F:45][C:46]([F:52])([F:51])[S:47](Cl)(=[O:49])=[O:48]>>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[CH2:29][CH3:30])[C:16]3[CH2:22][CH2:21][N:20]([S:47]([C:46]([F:52])([F:51])[F:45])(=[O:49])=[O:48])[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 79000Trifluoromethanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67178678HCID 67178678, compound

Product 1

HCID 59239414HCID 59239414, compound

Procedure

(S)-1-ethyl-3-(4-(4-(3-ethylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (0.0473 g, 0.115 mmol) in dry N,N-Dimethylformamide (0.60 mL, 7.7 mmol) was added N,N-Diisopropylethylamine (0.0636 mL, 0.365 mmol) followed by Trifluoromethanesulfonyl chloride (0.01940 mL, 0.1822 mmol). The reaction mixture was stirred for overnight. The reaction mixture was concentrated and was chromatographed through silica gel (4 g, 0-100% EtOAc in heptane followed by 10% MeOH in dichloromethane). The trifluoromethanesulfonamide was isolated and purified by HPLC. (S)-1-ethyl-3-(4-(4-(3-ethylmorpholino)-7-(trifluoromethylsulfonyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (xi): 1H NMR (400 MHz, DMSO) δ 8.66 (s, 1H), 8.16 (d, J=8.7, 2H), 7.48 (d, J=8.8, 2H), 6.18 (t, J=5.6, 1H), 4.68-4.52 (m, 2H), 4.01 (s, 1H), 3.82 (dd, J=26.3, 11.2, 3H), 3.69 (t, J=12.6, 3H), 3.54 (t, J=11.1, 1H), 3.49-3.38 (m, 1H), 3.18-3.06 (m, 2H), 2.87 (s, 1H), 2.75 (d, J=16.4, 1H), 1.80 (dd, J=11.3, 6.9, 2H), 1.06 (t, J=7.2, 3H), 0.83 (t, J=7.4, 3H). LC/MS-m/z+543.2 (M+H)+

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customwas chromatographed through silica gel (4 g, 0-100% EtOAc in heptane followed by 10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-acc6cea3069d4e1a9703f3ec70fc8687
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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