Diisopropylethylamine → HCID 67273951, compound

HRID 1698353Notes

Reaction equation

HRID 1698353 reaction equation
Cl.[CH:2]1[C:14]2[CH:13]([CH2:15][O:16][C:17]([N:19]3[CH2:24][C@H:23]([C:25](=[O:48])[N:26]([CH:45]4[CH2:47][CH2:46]4)[C:27]4[CH:28]=[CH:29][C:30]5[O:35][C:34]([CH3:37])([CH3:36])[C:33](=[O:38])[N:32]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[C:31]=5[CH:44]=4)[CH2:22][C@H:21]([NH2:49])[CH2:20]3)=[O:18])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:50]([C:52]1([C:55](O)=[O:56])[CH2:54][CH2:53]1)#[N:51].CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH:11]1[C:12]2[CH:13]([CH2:15][O:16][C:17]([N:19]3[CH2:24][C@H:23]([C:25](=[O:48])[N:26]([CH:45]4[CH2:47][CH2:46]4)[C:27]4[CH:28]=[CH:29][C:30]5[O:35][C:34]([CH3:36])([CH3:37])[C:33](=[O:38])[N:32]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[C:31]=5[CH:44]=4)[CH2:22][C@H:21]([NH:49][C:55]([C:52]4([C:50]#[N:51])[CH2:54][CH2:53]4)=[O:56])[CH2:20]3)=[O:18])[C:14]3[C:6](=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27332591-Cyanocyclopropanecarboxylic acidHCID 67272964HCID 67272964, compound

Product 1

HCID 67273951HCID 67273951, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S,5R)-3-Amino-5-{cyclopropyl-[4-(3-methoxy-propyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester hydrochloride salt (100 mg, 0.152 mmol) and 1-Cyano-cyclo-propanecarboxylic acid (20 mg, 0.182 mmol) in DMF (10 mL) is added EDC-HCl (45 mg, 0.227 mmol), HOAt (31 mg, 0.227 mmol) and diisopropylethylamine (0.04 mL, 0.227 mmol) at 0° C. The mixture is stirred for 14 h at r.t. and diluted with ethyl acetate, and washed with H2O. The organic layer is dried over MgSO4 and evaporated in vacuo. The residue is purified by silica-gel column chromatography to afford the title compound as a white solid. MS: 746 [M+H]+; tR (CombiScreen ODS-AM, 50×4.6 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 2 min, flow 2.0 ml/min): 2.14 min.

Workup

  1. washwashed with H2O
  2. dry with materialThe organic layer is dried over MgSO4
  3. customevaporated in vacuo
  4. customThe residue is purified by silica-gel column chromatography

Sources & evidence

ORD record
ord-1005c38efe054ddb8d19c518b46f8a4a
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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