4-Methylmorpholine → HCID 68311207, compound

HRID 529587Notes

Reaction equation

HRID 529587 reaction equation
ClC(OCC(C)C)=O.[CH2:9]([C@H:16]([C:43]([NH:45][C@H:46]1[CH2:52][CH2:51][S:50][C@H:49]2[CH2:53][CH2:54][CH2:55][C@@H:56]([C:57]([O:59][CH3:60])=[O:58])[N:48]2[C:47]1=[O:61])=O)[CH2:17][CH2:18][C@@H:19]([C:24](=[O:42])[NH:25][C@H:26]1[CH2:32][CH2:31][S:30][C@H:29]2[CH2:33][CH2:34][CH2:35][C@@H:36]([C:37]([O:39][CH3:40])=[O:38])[N:28]2[C:27]1=[O:41])[CH2:20][C:21](O)=[O:22])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN1CCOCC1.[NH4+:69].[OH-:70]>C(Cl)Cl>[NH2:69][C:21](=[O:22])[CH2:20][C@H:19]([C:24](=[O:42])[NH:25][C@H:26]1[CH2:32][CH2:31][S:30][C@H:29]2[CH2:33][CH2:34][CH2:35][C@@H:36]([C:37]([O:39][CH3:40])=[O:38])[N:28]2[C:27]1=[O:41])[CH2:18][CH2:17][C@H:16]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:43]([NH:45][C@H:46]1[CH2:52][CH2:51][S:50][C@H:49]2[CH2:53][CH2:54][CH2:55][C@@H:56]([C:57]([O:59][CH3:60])=[O:58])[N:48]2[C:47]1=[O:61])=[O:70]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 62365Isobutyl chloroformateHCID 68310550HCID 68310550, compound

Product 1

HCID 68311207HCID 68311207, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isobutyl chloroformate (3.0 mg, 0.022 mmol) was added to a 0° C. solution of (3R,6R)-6-benzyl-7-((4S,7S,10aS)-7-(methoxycarbonyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylamino)-3-((4S,7S,10aS)-7-(methoxycarbonyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamoyl)-7-oxoheptanoic acid (16 mg, 0.021 mmol) and NMM (2.5 mg, 0.025 mmol) in DCM (0.1 mL). After 30 min at 0° C., NH4OH (1.5 mg, 0.041 mmol) was added. The ice bath was removed and the reaction mixture was stirred at rt for 1 hr. The reaction mixture was concentrated. The residue was purified by RP prep-HPLC (Method A) to give methyl (4S,7S,10aS)-4-(((2R,5R)-7-amino-2-benzyl-5-(((4S,7S,10aS)-7-(methoxycarbonyl)-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepin-4-yl)carbamoyl)-7-oxoheptanoyl)amino)-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate (8.5 mg, 0.010 mmol, 53% yield) as a colorless oil. Anal. Calcd. for C37H51N5O9S2 m/z 773.7. found: 7749.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.53 (1H, d, J=6.6 Hz), 7.28-7.11 (6H, m), 6.38 (1H, br. s.), 6.18 (1H, br. s.), 5.43-5.36 (2H, m), 5.20-5.14 (1H, m), 5.14-5.00 (3H, m), 4.03-3.80 (2H, m), 3.72 (3H, s), 3.69 (3H, s), 3.25-3.08 (2H, m), 2.97-2.89 (1H, m), 2.89-2.80 (2H, m), 2.79-2.66 (2H, m), 2.61-2.36 (4H, m), 2.32 (1H, dd, J=14.8, 4.9 Hz), 2.24-2.15 (1H, m), 2.08-1.94 (4H, m), 1.86-1.76 (1H, m), 1.74-1.57 (8H, m), 1.57-1.46 (2H, m).

Workup

  1. customThe ice bath was removed
  2. concentrationThe reaction mixture was concentrated
  3. customThe residue was purified by RP prep-HPLC (Method A)

Sources & evidence

ORD record
ord-4c5d0bfece3c44aab71715c97ba3b458
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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