Isopropylamine → HCID 53380870, compound

HRID 1617420Notes

Reaction equation

HRID 1617420 reaction equation
CS(Cl)(=O)=O.O[CH2:7][C:8]1[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]=[C:10]([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([N:26]3[CH2:29][C:28]([CH2:52][C:53]#[N:54])([N:30]4[CH:34]=[C:33]([C:35]5[C:36]6[CH:43]=[CH:42][N:41](COCC[Si](C)(C)C)[C:37]=6[N:38]=[CH:39][N:40]=5)[CH:32]=[N:31]4)[CH2:27]3)[CH2:22][CH2:21]2)=[O:19])[CH:9]=1.C(N(CC)CC)C.[CH3:62][CH:63]([NH2:65])[CH3:64]>C(Cl)Cl>[CH:63]([NH:65][CH2:7][C:8]1[N:13]=[C:12]([C:14]([F:15])([F:16])[F:17])[N:11]=[C:10]([C:18]([N:20]2[CH2:21][CH2:22][CH:23]([N:26]3[CH2:29][C:28]([CH2:52][C:53]#[N:54])([N:30]4[CH:34]=[C:33]([C:35]5[C:36]6[CH:43]=[CH:42][NH:41][C:37]=6[N:38]=[CH:39][N:40]=5)[CH:32]=[N:31]4)[CH2:27]3)[CH2:24][CH2:25]2)=[O:19])[CH:9]=1)([CH3:64])[CH3:62]

Participants

6

Reactant 4

HCID 6363Isopropylamine2×HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 58431331HCID 58431331, compound

Product 1

HCID 53380870HCID 53380870, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

Methanesulfonyl chloride (2.8 0.036 mmol) in methylene chloride (0.20 mL) was added to a mixture of {1-(1-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile (21 mg, 0.030 mmol, prepared as in Example 376, Step E) and triethylamine (8.4 μL, 0.060 mmol) in methylene chloride (1.0 mL) at 0° C. After 15 minutes, 2-propanamine (20 μL, 0.3 mmol) was added. The mixture was then heated to 40° C. After 1.5 hours, additional 2-Propanamine (20 μL, 0.3 mmol, Aldrich) was added and the reaction heated for a total of 3 hours at this temperature. The mixture was concentrated in vacuo. The residue was stirred for 1 hour in a 1:1 mixture of TFA/DCM, then concentrated again. The residue was redissolved in MeOH (1.0 mL) and ethylenediamine (0.2 mL) was added. The product was purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: 11.6 mg (63%); LC-MS: 608.4 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 12.15 (br s, 1H), 8.82 (s, 1H), 8.69 (s, 1H), 8.42 (s, 1H), 7.97 (s, 1H), 7.61 (d, 1H), 7.07 (d, 1H), 41.2-4.02 (m, 1H), 3.94 (s, 2H), 3.75 (dd, 2H), 3.63-3.45 (m, 5H), 3.31-3.22 (m, 1H), 3.16-3.06 (m, 1H), 2.75 (septet, 1H), 2.61-2.53 (m, 1H), 1.84-1.75 (m, 1H), 1.70-1.60 (m, 1H), 1.36-1.19 (m, 2H), 1.01 (d, 6H). 19F NMR (400 MHz, DMSO-d6): δ −69.46 (s, 3F).

Workup

  1. waitAfter 1.5 hours
  2. temperaturethe reaction heated for a total of 3 hours at this temperature
  3. concentrationThe mixture was concentrated in vacuo
  4. concentrationconcentrated again
  5. dissolutionThe residue was redissolved in MeOH (1.0 mL)
  6. additionethylenediamine (0.2 mL) was added
  7. customThe product was purified via preparative HPLC-MS (C18
  8. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-108e4d959b974fc18eabcca52873f7e0
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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