Dimethylformamide → HCID 87332231, compound

HRID 2113956Notes

Reaction equation

HRID 2113956 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=3)[N:9]=2)=[C:5]([CH3:7])[N:6]=1.[NH:24]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25][CH2:26]C(O)=O.C(N=C=NC(C)C)(C)C.CN(C=[O:50])C>>[C:33]([O:32][C:30](=[O:31])[NH:24][CH2:25][C:26](=[O:50])[NH:1][C:2]1[S:3][C:4]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=3)[N:9]=2)=[C:5]([CH3:7])[N:6]=1)([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 4479614-(2-Amino-4-methyl-5-thiazolyl)-N-(3-nitrophenyl)-2-pyrimidinamine

Product 1

HCID 87332231HCID 87332231, compound

Procedure

A mixture of [4-(2-amino-4-methyl-thiazol-5-yl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine (0.12 g, 0.37 mmol), Boc-βAla-OH (0.18 g, 0.93 mmol), 1,3-diisopropylcarbodiimide (0.07 mL, 0.45 mmol) and 4-N,N-dimethylaminopyridine (36 mg, 0.3 mmol) in of dry DMF (2 mL) was stirred at room temperature for 24 h. The reaction mixture was poured into ice water and extracted with EtOAc. The organics were combined and washed with brine, filtered, and dried on MgSO4. The solvent was evaporated to give brown residue, which was purified by SiO2 chromatography (1:1 EtOAc/PE) to afford ({4-Methyl-5-[2-(3-nitro-phenylamino)-pyrimidin-4-yl]-thiazol-2-ylcarbamoyl}-methyl)-carbamic acid tert-butyl ester as light yellow solid. Anal. RP-HPLC: tR=19.5 min (0-60% MeCN in 0.1% aq CF3COOH over 20 min, 1 mL/min, purity>93%). 1H-NMR (DMSO-d6) δ: 1.11 (s, 9H, CH3), 2.54 (s, 3H, CH3), 3.62 (m, 2H, CH2), 5.38 (m, 2H, CH2), 7.06 (d, 1H, J=5.5 Hz, pyrimidinyl-H), 7.46 (m, 1H, Ph-H), 7.72 (m, 1H, Ph-H), 8.15 (m, 1H, Ph-H), 8.45 (d, 1H, J=5.2 Hz, pyrimidinyl-H), 8.77 (s, 1H, NH). A solution of this material (97 mg, 0.19 mmol) in dioxane (5 mL) was treated with CF3COOH (1 ml). After stirring at room temperature for 22 h, the reaction mixture was evaporated and purified by preparative RP-HPLC (0-60% MeCN in 0.1% aq CF3COOH over 40 min, 9 mL/min) to afford the titled compound (34 mg) as a light yellow solid. Anal. RP-HPLC: tR=14.0 min (0-60% MeCN in 0.1% aq CF3COOH over 20 min, 1 mL/min, purity>93%). 1H-NMR (CD3OD) δ: 2.64 (s, 3H, CH3), 3.30 (m, 2H, CH2), 3.33 (m, 2H, CH2), 7.14 (d, 1H, J=5.5 Hz, pyrimidinyl-H), 7.52 (t, 1H, J=8.2 Hz, Ph-H), 7.63 (m, 1H, Ph-H), 7.96 (m, 1H, Ph-H), 8.46 (d, 1H, J=5.5 Hz, pyrimidinyl-H), 8.88 (s, 1H, NH). MS (ESi+) m/z 400.6 (C17H17N7O3S requires 399.4).

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. filtrationfiltered
  4. customdried on MgSO4
  5. customThe solvent was evaporated
  6. customto give brown residue, which
  7. customwas purified by SiO2 chromatography (1:1 EtOAc/PE)

Sources & evidence

ORD record
ord-56196842180a40ab9a8a6fc1f5171fbf
Source dataset
uspto-grants-2008_10
Patent number
US07432260B2

Reaction notes

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