Methanol → HCID 178476987, compound

HRID 472105Notes

Reaction equation

HRID 472105 reaction equation
[CH3:1][N:2]([C:20]1[C:21]2[CH:28]=[CH:27][NH:26][C:22]=2[N:23]=[CH:24][N:25]=1)[C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][S:10]([N:13]2[CH2:18][CH2:17][CH2:16][C@@H:15]([OH:19])[CH2:14]2)(=[O:12])=[O:11])[CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[P:38](OCl)([O:43][CH2:44][CH3:45])([O:40][CH2:41][CH3:42])=[O:39].CO>ClCCl>[P:38]([O:19][C@@H:15]1[CH2:16][CH2:17][CH2:18][N:13]([S:10]([CH2:9][C@H:6]2[CH2:5][CH2:4][C@H:3]([N:2]([CH3:1])[C:20]3[C:21]4[CH:28]=[CH:27][NH:26][C:22]=4[N:23]=[CH:24][N:25]=3)[CH2:8][CH2:7]2)(=[O:12])=[O:11])[CH2:14]1)([O:43][CH2:44][CH3:45])([O:40][CH2:41][CH3:42])=[O:39]

Participants

6

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 22262455HCID 22262455, compoundHCID 178482410HCID 178482410, compound

Product 1

HCID 178476987HCID 178476987, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(3R)-1-[({trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-methyl)sulfonyl]piperidin-3-ol (100 mg, 0.24 mmol) was suspended in dichloromethane (5 mL). Diisopropylethylamine (0.05 mL, 0.3 mmol) was added followed by diethyl chloro phosphate (0.036 mL, 0.24 mmol). The reaction mixture was stirred under nitrogen overnight. Methanol (1 mL) was added to the flask and the reaction mixture was concentrated in vacuo and the resulting residue was purified by preparative reverse phase HPLC. (100 mg, 75%) 1H NMR (400 MHz, DMSO-d6) ppm 1.19 (t, J=6.95 Hz, 6H) 1.23-1.29 (m, 3H) 1.40-1.49 (m, 1H) 1.64-1.76 (m, 5H) 1.80 (d, J=12.81 Hz, 1H) 1.87 (d, J=3.66 Hz, 1H) 2.02 (d, J=10.98 Hz, 2H) 2.58 (dd, J=10.98, 8.42 Hz, 1H) 2.73-2.81 (m, 1H) 2.88-2.99 (m, 2H) 3.15 (s, 3H) 3.44-3.55 (m, 2H) 4.05-4.12 (m, 2H) 4.14-4.21 (m, 2H) 5.00 (d, J=4.03 Hz, 1H) 6.79 (br. s., 1H) 7.27 (dd, J=3.66, 2.20 Hz, 1H) 8.23 (s, 1H). LCMS m/z 544.8 (M+H calcd for C23H38N5O6PS requires 543.2). LCMS (C-18 column, gradient elution 5 minute chromatograph, 95:5 to 5:95 water/acetonitrile, retention time 1.81 min).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customthe resulting residue was purified by preparative reverse phase HPLC
  3. washLCMS (C-18 column, gradient elution 5 minute chromatograph, 95:5 to 5:95 water/acetonitrile, retention time 1.81 min)

Sources & evidence

ORD record
ord-c547d2c099f743a4873dc8a0036f8bf1
Source dataset
uspto-grants-2014_01
Patent number
US08633206B2

Reaction notes

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