Diisopropylethylamine → HCID 68260894, compound

HRID 2047359Notes

Reaction equation

HRID 2047359 reaction equation
F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.[F:25][C:26]1[CH:27]=[C:28]([CH2:33][C@@H:34]([CH2:38][NH:39][C:40]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[O:41])[C:35]([OH:37])=O)[CH:29]=[CH:30][C:31]=1[F:32].NCC(CC1C=CC=CC=1)C([NH:55][C:56]1[S:57][C:58]([Cl:68])=[C:59]([C:61]2[N:65]([CH3:66])[N:64]=[CH:63][C:62]=2[Cl:67])[CH:60]=1)=O.C(N(CC)C(C)C)(C)C>ClCCl>[Cl:68][C:58]1[S:57][C:56]([NH:55][C:35](=[O:37])[C@@H:34]([CH2:33][C:28]2[CH:29]=[CH:30][C:31]([F:32])=[C:26]([F:25])[CH:27]=2)[CH2:38][NH:39][C:40](=[O:41])[O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:60][C:59]=1[C:61]1[N:65]([CH3:66])[N:64]=[CH:63][C:62]=1[Cl:67]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 45377097HCID 45377097, compoundHCID 58388234HCID 58388234, compound

Product 1

HCID 68260894HCID 68260894, compoundYield 20.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Bromo-tris-pyrrolidino phosphoniumhexafluorophosphate (401 mg, 0.859 mmol) was added in one portion to a solution of (2S)-3-(3,4-difluorophenyl)-2-[({[(phenylmethyl)oxy]carbonyl}amino)methyl]propanoic acid (200 mg, 0.573 mmol)[prepared in Preparation 4] and [5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thienyl]amine-HCl (163 mg, 0.573 mmol)[prepared in Example 3] in N,N-diisopropylethylamine (0.500 ml, 2.86 mmol) and dichloromethane (7.174 ml). After 12 h, the solution was dry loaded onto silica and purified by chromatography (0-50% EtOAc in hexanes) affording phenylmethyl {(2S)-3-{[5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thienyl]amino}-2-[(3,4-difluorophenyl)methyl]-3-oxopropyl}carbamate (70 mg, 0.115 mmol, 20.05% yield) as an orange solid: LCMS (ES) m/e 579, 581 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) d ppm 11.61 (s, 1 H) 7.67 (s, 1 H) 7.53 (br. s., 1 H) 7.32 (s, 7 H) 7.03 (br. s., 1 H) 6.55 (s, 1 H) 5.01 (s, 2 H) 3.68 (s, 3 H) 3.19-3.28 (m, 2 H) 2.76-3.00 (m, 3 H).

Workup

  1. customthe solution was dry
  2. custompurified by chromatography (0-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ea19ccb3636c4b9e8dab6fc208201948
Source dataset
uspto-grants-2013_11
Patent number
US08592475B2

Reaction notes

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