1-Pyrrolidineethanamine → 3-(2-(3-(Benzyloxy)pyridin-2-ylamino)thiazol-4-yl)-N-(2-(pyrrolidin-1-yl)ethyl)propanamide

HRID 1426140Notes

Reaction equation

HRID 1426140 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]2[S:17][CH:18]=[C:19]([CH2:21][CH2:22][C:23]([OH:25])=O)[N:20]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:26]1([CH2:31][CH2:32][NH2:33])[CH2:30][CH2:29][CH2:28][CH2:27]1.O.N1(O)C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>>[CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]2[S:17][CH:18]=[C:19]([CH2:21][CH2:22][C:23]([NH:33][CH2:32][CH2:31][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:25])[N:20]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 13441-PyrrolidineethanamineHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 592256533-(2-(3-(Benzyloxy)pyridin-2-ylamino)thiazol-4-yl)propanoic acid

Product 1

HCID 166608433-(2-(3-(Benzyloxy)pyridin-2-ylamino)thiazol-4-yl)-N-(2-(pyrrolidin-1-yl)ethyl)propanamide

Conditions

Temperature
0 °C

Procedure

3-(2-(3-(Benzyloxy)pyridin-2-ylamino)thiazol-4-yl)propanoic acid (40 mg, 0.113 mmol), 2-(pyrrolidin-1-yl)ethanamine (0.0171 mL, 0.135 mmol), 1H-benzo[d][1,2,3]triazol-1-ol hydrate (22.4 mg, 0.146 mmol) and 4-methylmorpholine (0.0173 ml, 0.158 mmol) were placed in an 8.5 mL screw-cap vial. The reaction mixture was cooled to 0° C. in an ice bath, and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (33.0 mg, 0.172 mmol) was added as a solid. The mixture was stirred at 0° C. and then allowed to warm to room temp overnight. The reaction mixture was concentrated under high vacuum to remove DMF, and the residue was partitioned between dichloromethane and saturated aqueous NaHCO3 diluted with an equal part of water. The organic phase was washed with once with water, then with brine, and dried by passing through a plug of anhydrous sodium sulfate. The solution was concentrated in vacuo and dried under high vacuum to provide the title compound as a colorless oil. 1H NMR (CDCl3) δ 1.76 (s, 4H), 2.56 (m, 4H), 2.59 (dd, J=5.6, 12.9 Hz, 4H), 3.01-2.94 (m, 4H), 3.37 (dd, J=11.3, 5.5 Hz, 2H), 5.13 (s, 2H), 6.75 (bs, 1H), 6.47 (s, 1H), 6.82 (dd, J=8.2, 5.1 Hz, 2H), 7.10 (dd, J=1.2, 7.9, Hz, 1H), 7.42 (br s, 4H), 7.94 (dd, J=1.2, 5 Hz, 1H), 8.59 (bs, 1H); Mass spectrum (apci) m/z=452.2 (M+H).

Workup

  1. customscrew-cap vial
  2. temperatureto warm to room temp overnight
  3. concentrationThe reaction mixture was concentrated under high vacuum
  4. customto remove DMF
  5. customthe residue was partitioned between dichloromethane and saturated aqueous NaHCO3
  6. additiondiluted with an equal part of water
  7. washThe organic phase was washed with once with water
  8. dry with materialwith brine, and dried
  9. concentrationThe solution was concentrated in vacuo
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-c45b8114335440cd883d47a0ad46648f
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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